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Sample records for advanced diabetic retinopathy

  1. Advances in diabetic retinopathy

    PubMed Central

    Agarwal, Prakashchand; Jindal, Ankita; Saini, V.K.; Jindal, Sushil

    2014-01-01

    Diabetic retinopathy (DR) is a complication of long-term diabetes mellitus (DM). Over the last 2 decades lot of work has been on early diagnosis of DR and screening programs have been designed to help the masses. Large numbers of clinical studies have been done for patients of diabetes and DR wherein the role of blood sugar control, metabolic control, role of oral medicines for DR, role of imaging, fluorescein angiography, and retinal photocoagulation has been studied. Newer treatment modalities are being devised and studied for better patient care. We discuss these issues in our review highlight and newer advances over the last few years. PMID:25364670

  2. Diabetic Retinopathy

    MedlinePlus

    ... Cases of Diabetic Retinopathy (in thousands) by Age, Gender, and Race/Ethnicity Diabetic retinopathy affects men and ... Cases of Diabetic Retinopathy (in thousands) by Age, Gender, and Race/Ethnicity Projections for Diabetic Retinopathy (2010- ...

  3. Diabetic Retinopathy

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetic Retinopathy What Is Diabetic Retinopathy? Click for more information Can Cause Vision Loss, Blindness Diabetic retinopathy is a complication of diabetes and a leading ...

  4. Diabetic retinopathy.

    PubMed

    Wong, Tien Y; Cheung, Chui Ming Gemmy; Larsen, Michael; Sharma, Sanjay; Simó, Rafael

    2016-01-01

    Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is a major cause of vision loss in middle-aged and elderly people. One-third of people with diabetes have DR. Severe stages of DR include proliferative DR, caused by the abnormal growth of new retinal blood vessels, and diabetic macular oedema, in which there is exudation and oedema in the central part of the retina. DR is strongly associated with a prolonged duration of diabetes, hyperglycaemia and hypertension. It is traditionally regarded as a microvascular disease, but retinal neurodegeneration is also involved. Complex interrelated pathophysiological mechanisms triggered by hyperglycaemia underlie the development of DR. These mechanisms include genetic and epigenetic factors, increased production of free radicals, advanced glycosylation end products, inflammatory factors and vascular endothelial growth factor (VEGF). Optimal control of blood glucose and blood pressure in individuals with diabetes remains the cornerstone for preventing the development and arresting the progression of DR. Anti-VEGF therapy is currently indicated for diabetic macular oedema associated with vision loss, whereas laser photocoagulation prevents severe vision loss in eyes with proliferative DR. These measures, together with increasing public awareness and access to regular screening for DR with retinal photography, and the development of new treatments to address early disease stages, will lead to better outcomes and prevent blindness for patients with DR. PMID:27159554

  5. Treatment of diabetic retinopathy: Recent advances and unresolved challenges

    PubMed Central

    Stewart, Michael W

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  6. Treatment of diabetic retinopathy: Recent advances and unresolved challenges.

    PubMed

    Stewart, Michael W

    2016-08-25

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  7. Dyslipidemia and Diabetic Retinopathy

    PubMed Central

    Chang, Yo-Chen; Wu, Wen-Chuan

    2013-01-01

    Diabetic retinopathy (DR) is one of the major microvascular complications of diabetes. In developed countries, it is the most common cause of preventable blindness in diabetic adults. Dyslipidemia, a major systemic disorder, is one of the most important risk factors for cardiovascular disease. Patients with diabetes have an increased risk of suffering from dyslipidemia concurrently. The aim of this article is to review the association between diabetic retinopathy (DR) and traditional/nontraditional lipid markers, possible mechanisms involving lipid metabolism and diabetic retinopathy, and the effect of lipid-lowering therapies on diabetic retinopathy. For traditional lipid markers, evidence is available that total cholesterol and low-density lipoprotein cholesterol are associated with the presence of hard exudates in patients with DR. The study of nontraditional lipid markers is advancing only in recently years. The severity of DR is inversely associated with apolipoprotein A1 (ApoA1), whereas ApoB and the ApoB-to-ApoA1 ratio are positively associated with DR. The role of lipid-lowering medication is to work as adjunctive therapy for better control of diabetes-related complications including DR. PMID:24380088

  8. Advances in retinal imaging for diabetic retinopathy and diabetic macular edema.

    PubMed

    Tan, Colin Siang Hui; Chew, Milton Cher Yong; Lim, Louis Wei Yi; Sadda, Srinivas R

    2016-01-01

    Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease. PMID:26953028

  9. Advances in retinal imaging for diabetic retinopathy and diabetic macular edema

    PubMed Central

    Tan, Colin Siang Hui; Chew, Milton Cher Yong; Lim, Louis Wei Yi; Sadda, Srinivas R

    2016-01-01

    Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease. PMID:26953028

  10. Fenofibrate and Diabetic Retinopathy.

    PubMed

    Knickelbein, Jared E; Abbott, Akshar B; Chew, Emily Y

    2016-10-01

    Diabetic retinopathy, a common and sight-threatening microvascular complication of diabetes mellitus, is a leading cause of blindness among working-aged adults. Medical therapies including intensive control of hyperglycemia and hypertension have been shown to reduce the incidence and progression of diabetic retinopathy. The association of dyslipidemia and treatment with statins with diabetic retinopathy is inconsistent in epidemiologic studies. However, two recent randomized clinical trials have demonstrated beneficial effects of systemic fenofibrate therapy in reducing the progression of diabetic retinopathy independently of serum lipid levels. These findings suggest that fenofibrate may be an effective strategy for reducing the progression of diabetic retinopathy, thus reducing the large and growing public health burden of treating the sight-threatening complications of diabetic retinopathy. PMID:27525681

  11. Teleophthalmology in Diabetic Retinopathy

    PubMed Central

    Raman, Rajiv

    2014-01-01

    Over the past decade, there have been rapid strides in progress in the fields of telecommunication and medical imaging. There is growing evidence regarding use of teleophthalmology for screening of diabetic retinopathy. This article highlights some pertinent questions regarding use of telescreening for diabetic retinopathy. It deals with evidence regarding accuracy of diagnosis, patients satisfaction and cost-effectiveness. The American Telemedicine Association have given certain guidelines for teleheath practices for diabetic retinopathy. The article discusses regarding these guidelines. Finally, a working model for diabetic retinopathy screening through teleophthalmology has been described. Telescreening for diabetic retinopathy seems to be a cost-effective, accurate, and reliable method for screening for diabetic retinopathy. The American Telemedicine Association has set up guidelines for telescreening that should be adhered to provide quality screening services to people with diabetes. PMID:24876576

  12. Diabetic Retinopathy: Nature and Extent.

    ERIC Educational Resources Information Center

    Coughlin, W. Ronald; Patz, Arnall

    1978-01-01

    The authors discuss the incidence and prevalence of diabetic retinopathy in juvenile and maturity onset diabetics, background and proliferative retinopathy, and current modalities of treatment. (Author)

  13. Non-Proliferative Diabetic Retinopathy Vision Simulator

    MedlinePlus

    ... Diabetic Retinopathy Vision Simulator Non-Proliferative Diabetic Retinopathy Vision Simulator Mar. 03, 2014 How does non-proliferative diabetic retinopathy affect your vision? Nonproliferative diabetic retinopathy, also known as background retinopathy, ...

  14. The renin-angiotensin system and advanced glycation end-products in diabetic retinopathy: impacts and synergies.

    PubMed

    Miller, Antonia G; Zhu, Tong; Wilkinson-Berka, Jennifer L

    2013-11-01

    Diabetic retinopathy is a major cause of vision impairment and blindness and represents a significant health burden throughout the world. There is considerable interest in developing new treatments that retard the progression of diabetic retinopathy from its early to proliferative stages. It could be argued that the absence of an ideal therapy for diabetic retinopathy comes from an incomplete understanding about the biochemical mechanisms that underlie this disease, and their precise impact on specific retinal cell populations. Findings from pre-clinical and clinical studies indicate that both the renin-angiotensin system (RAS) and advanced glycation end-products (AGEs) influence various aspects of diabetic retinopathy. Of interest is growing evidence of cross-talk between the RAS and AGEs pathways. This review will discuss the role of both the RAS and AGEs in diabetic retinopathy, and how the identification of interactions between the two pathways may have implications for the development of new treatment strategies. PMID:23173957

  15. Diabetic Retinopathy

    MedlinePlus

    ... eye, including the retina, macula, lens and the optic nerve. Diabetic eye disease is a group of ... a group of diseases that damage the eye’s optic nerve—the bundle of nerve fibers that connects ...

  16. Biomarkers in Diabetic Retinopathy.

    PubMed

    Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  17. Novelties in Diabetic Retinopathy.

    PubMed

    Ebneter, Andreas; Zinkernagel, Martin S

    2016-01-01

    Although diabetic retinopathy (DR) remains a leading cause of vision loss, the last decade has brought significant advances in the diagnosis and treatment of this common complication of diabetes mellitus. First, optical coherence tomography allows for noninvasive imaging of the retina, in particular, the macula, with very high resolution, thus facilitating the management of diabetic macular edema. In addition, recent advances in the understanding of the pathophysiology of DR, in particular, the key role of cytokines, such as vascular endothelial growth factor (VEGF), have led to the development of anti-VEGF antibodies for intraocular use. Anti-VEGF therapies have largely replaced laser photocoagulation for the treatment of diabetic macular edema. The benefit of intravitreal anti-VEGF in diabetic macular edema has been proven in numerous large randomized controlled trials. Moreover, a role of inflammation in DR has been recognized, and several mainly steroid-based, anti-inflammatory agents for intravitreal treatment have been shown to be effective. Despite these recent advances, strict systemic control of glycemia remains the cornerstone of the management of DR, significantly reducing ocular complications. This chapter will provide an overview of current and novel concepts of DR and will allude to promising novel therapeutic options for this sight-threatening disease. PMID:26824524

  18. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

    PubMed

    Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

    2016-02-01

    Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided. PMID:26807609

  19. Diabetic retinopathy - ocular complications of diabetes mellitus

    PubMed Central

    Nentwich, Martin M; Ulbig, Michael W

    2015-01-01

    In industrialized nations diabetic retinopathy is the most frequent microvascular complication of diabetes mellitus and the most common cause of blindness in the working-age population. In the next 15 years, the number of patients suffering from diabetes mellitus is expected to increase significantly. By the year 2030, about 440 million people in the age-group 20-79 years are estimated to be suffering from diabetes mellitus worldwide (prevalence 7.7%), while in 2010 there were 285 million people with diabetes mellitus (prevalence 6.4%). This accounts for an increase in patients with diabetes in industrialized nations by 20% and in developing countries by 69% until the year 2030. Due to the expected rise in diabetic patients, the need for ophthalmic care of patients (i.e., exams and treatments) will also increase and represents a challenge for eye-care providers. Development of optimized screening programs, which respect available resources of the ophthalmic infrastructure, will become even more important. Main reasons for loss of vision in patients with diabetes mellitus are diabetic macular edema and proliferative diabetic retinopathy. Incidence or progression of these potentially blinding complications can be greatly reduced by adequate control of blood glucose and blood pressure levels. Additionally, regular ophthalmic exams are mandatory for detecting ocular complications and initiating treatments such as laser photocoagulation in case of clinical significant diabetic macular edema or early proliferative diabetic retinopathy. In this way, the risk of blindness can considerably be reduced. In advanced stages of diabetic retinopathy, pars-plana vitrectomy is performed to treat vitreous hemorrhage and tractional retinal detachment. In recent years, the advent of intravitreal medication has improved therapeutic options for patients with advanced diabetic macular edema. PMID:25897358

  20. Neuropeptides and diabetic retinopathy

    PubMed Central

    Gábriel, Robert

    2013-01-01

    Diabetic retinopathy, a common complication of diabetes, develops in 75% of patients with type 1 and 50% of patients with type 2 diabetes, progressing to legal blindness in about 5%. In the recent years, considerable efforts have been put into finding treatments for this condition. It has been discovered that peptidergic mechanisms (neuropeptides and their analogues, activating a diverse array of signal transduction pathways through their multiple receptors) are potentially important for consideration in drug development strategies. A considerable amount of knowledge has been accumulated over the last three decades on human retinal neuropeptides and those elements in the pathomechanisms of diabetic retinopathy which might be related to peptidergic signal transduction. Here, human retinal neuropeptides and their receptors are reviewed, along with the theories relevant to the pathogenesis of diabetic retinopathy both in humans and in experimental models. By collating this information, the curative potential of certain neupeptides and their analogues/antagonists can also be discussed, along with the existing clinical treatments of diabetic retinopathy. The most promising peptidergic pathways for which treatment strategies may be developed at present are stimulation of the somatostatin-related pathway and the pituitary adenylyl cyclase-activating polypeptide-related pathway or inhibition of angiotensinergic mechanisms. These approaches may result in the inhibition of vascular endothelial growth factor production and neuronal apoptosis; therefore, both the optical quality of the image and the processing capability of the neural circuit in the retina may be saved. PMID:23043302

  1. Imaging in Diabetic Retinopathy

    PubMed Central

    Salz, David A.; Witkin, Andre J.

    2015-01-01

    While the primary method for evaluating diabetic retinopathy involves direct and indirect ophthalmoscopy, various imaging modalities are of significant utility in the screening, evaluation, diagnosis, and treatment of different presentations and manifestations of this disease. This manuscript is a review of the important imaging modalities that are used in diabetic retinopathy, including color fundus photography, fluorescein angiography, B-scan ultrasonography, and optical coherence tomography. The article will provide an overview of these different imaging techniques and how they can be most effectively used in current practice. PMID:25949070

  2. Learn the Facts about Diabetic Retinopathy

    MedlinePlus

    ... FACTS A D bo I ut ABETIC RETINOPATHY Diabetic retinopathy occurs when diabetes damages the tiny blood ... National Eye Institute, 2014 GR A OWING ISSUE Diabetic retinopathy is the leading cause of blindness in ...

  3. Diabetic Retinopathy and Systemic Factors

    PubMed Central

    Frank, Robert N.

    2015-01-01

    Diabetic retinopathy, an oculardisease, is governed by systemic as well as local ocular factors. These include primarily chronic levels of blood glucose. Individuals with chronically elevated blood glucose levels have substantially more, and more severe, retinopathy than those with lower blood glucose levels. The relationship of blood glucose to retinopathy is continuous, with no threshold although individuals with hemoglobin A1c levels (a measure of chronic glycemia) <6.5%, generally develop little or no retinopathy. Blood pressure levels have been claimed to influence retinopathy development and progression, but multiple controlled clinical trials of antihypertensive agents in diabetic subjects have produced only weak evidence of benefit from blood pressure lowering on the incidence and progression of diabetic retinopathy. Elevated blood lipids seem to play a role in the progression of retinopathy, and two trials of fenofibrate, a lipid-lowering agent that has not proved effective in preventing cardiovascular disease, have shown benefit in preventing retinopathy progression. The mechanism of this effect may not, however, be directly related to the reduction in blood lipids. Finally, there is strong, but only circumstantial, evidence for a genetic or epigenetic influence on the pathogenesis of diabetic retinopathy. Despite the power of large-scale epidemiologic studies and modern molecular biological and computational techniques, the gene or genes, which predispose or protect against the development and progression of diabetic retinopathy remain elusive. PMID:25949071

  4. Antioxidants and diabetic retinopathy.

    PubMed

    Williams, Michael; Hogg, Ruth E; Chakravarthy, Usha

    2013-08-01

    The biochemical perturbations in diabetes mellitus (DM) create the conditions for the production of free radicals, the consequence of which is increased oxidative stress. Evidence has accrued over the past 2 decades that suggests that oxidative stress is an important pathogenetic factor in the development of diabetic retinopathy (DR). Experimental data show that the use of strategies that ameliorate oxidative stress can prevent and retard the development of DR in the animal model. Clinical observations also suggest that reducing oxidative stress may help to reverse pathological manifestations of DR. The present article constitutes an examination of the role of antioxidants in the management of DR and the current state of clinically relevant knowledge. PMID:23649947

  5. New treatments for diabetic retinopathy.

    PubMed

    Das, A; Stroud, S; Mehta, A; Rangasamy, S

    2015-03-01

    Diabetic retinopathy is the major cause of vision loss in middle-aged adults. Alteration of the blood-retinal barrier (BRB) is the hallmark of diabetic retinopathy and, subsequently, hypoxia may result in retinal neovascularization. Tight control of systemic factors such as blood glucose, blood pressure and blood lipids is essential in the management of this disease. Vascular endothelial growth factor (VEGF) is one of the most important factors responsible for alteration of the BRB. The introduction of anti-VEGF agents has revolutionized the therapeutic strategies used in people with diabetic retinopathy, and the use of laser therapy has been modified. In the present article, we examine the clinical features and pathophysiology of diabetic retinopathy and review the current status of new treatment recommendations for this disease, and also explore some possible future therapies. PMID:25160598

  6. Association between diabetic retinopathy and hemoglobin level

    PubMed Central

    Bahar, Adele; Kashi, Zahra; Ahmadzadeh Amiri, Ahmad; Nabipour, Majid

    2013-01-01

    Background: Anemia may be considered to be an independent risk factor for the development of diabetic retinopathy (DR) in patients with renal failure. The purpose of this study was to investigate the association between blood hemoglobin level and retinopathy in diabetic patients with normal renal function tests. Methods: From 2009 to 2011, 1100 diabetic patients underwent retinal examination. Among them, 159 subjects were diagnosed to have DR and were compared with 318 diabetic subjects with normal retinal examination as the control group. The level of hemoglobin (Hb), Hb A1C, serum iron, ferritin, and total iron binding capacity were compared between these two groups. Results: Among the 159 patients with DR, 112 (70.4%) had mild to moderate no proliferative retinopathy (NPDR) and 47 (29.6%) had advanced retinopathy (severe NPDR or proliferative). The mean hemoglobin level in case and control group was 12.15±1.50 and 12.73±1.38 g/dl, respectively (p<0.001). Anemia was seen in 45.9% and 26.1% in the case and the control groups, respectively (p<0.001). Ferritin <15ng/ml was seen in 7.4% and 6.1% of patients with and without DR, respectively (p=0.8). Conclusion: The results show that diabetic patients with retinopathy have lower level of hemoglobin and higher frequency of anemia. It is suggested that the level of hemoglobin should be evaluated periodically in diabetic patients. PMID:24294469

  7. Advances in the management of diabetic macular oedema based on evidence from the Diabetic Retinopathy Clinical Research Network

    PubMed Central

    Lim, Lik Thai; Chia, Seen Nee; Ah-kee, Elliott Yann; Chew, Nejia; Gupta, Manish

    2015-01-01

    The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient’s clinical history and assessment. PMID:26034315

  8. Diabetic retinopathy – An update

    PubMed Central

    Alghadyan, Abdulrahman A.

    2011-01-01

    Management of diabetes should involve both systemic and ocular aspects. Control of hyperglycemia, hypertension and dyslipidemia are of major role in the management of diabetic retinopathy. In the ocular part; laser treatment remains the cornerstone of treatment of diabetic macular edema (focal/grid), severe non-proliferative and proliferative diabetic retinopathy (panretinal photocoagulation). There is a strong support to combination therapy. Using one or two intravitreal injections such as anti-VEGF and or steroid to reduce central macular thickness followed by focal or grid laser to give a sustained response may offer an alternative to treatment in diabetic macular edema. Anti-VEGF were found to be effective as an adjunct therapy in proliferative diabetic retinopathy patient who is going to have vitrectomy for vitreous hemorrhage with neovascularization, panretinal photocoagulation, and other ocular surgery such as cases with neovascular glaucoma and cataract with refractory macular edema. PMID:23960911

  9. Vitreous Proteomics and Diabetic Retinopathy

    PubMed Central

    Walia, Saloni; Clermont, Allen C.; Gao, Ben-Bo; Aiello, Lloyd Paul; Feener, Edward P.

    2016-01-01

    Diabetic retinopathy is the major cause of acquired blindness in working age adults. Studies of the vitreous proteome have provided insights into the etiology of diabetic retinopathy and suggested potential molecular targets for treatments. Further characterization of the protein changes associated with the progression of this disease may suggest additional therapeutic approaches as well as reveal novel factors that may be useful in predicting risk and functional outcomes of interventional therapies. This article provides an overview of the various techniques used for proteomic analysis of the vitreous and details results from studies evaluating vitreous of diabetic patients using the proteomic approach. PMID:21091014

  10. Epigenetic modifications and diabetic retinopathy.

    PubMed

    Kowluru, Renu A; Santos, Julia M; Mishra, Manish

    2013-01-01

    Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s) responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease. PMID:24286082

  11. Genetic components in diabetic retinopathy

    PubMed Central

    Mishra, Bibhudatta; Swaroop, Anand; Kandpal, Raj P

    2016-01-01

    Diabetic retinopathy (DR) is a serious complication of diabetes, which is fast reaching epidemic proportions worldwide. While tight glycemic control remains the standard of care for preventing the progression of DR, better insights into DR etiology require understanding its genetic basis, which in turn may assist in the design of novel treatments. During the last decade, genomic medicine is increasingly being applied to common multifactorial diseases such as diabetes and age-related macular degeneration. The contribution of genetics to the initiation and progression of DR has been recognized for some time, but the involvement of specific genes and genetic variants remains elusive. Several investigations are currently underway for identifying DR susceptibility loci through linkage studies, candidate gene approaches, and genome-wide association studies. Advent of next generation sequencing and high throughput genomic technologies, development of novel bioinformatics tools and collaborations among research teams should facilitate such investigations. Here, we review the current state of genetic studies in DR and discuss reported findings in the context of biochemical, cell biological and therapeutic advances. We propose the development of a consortium in India for genetic studies with large cohorts of patients and controls from limited geographical areas to stratify the impact of the environment. Uniform guidelines should be established for clinical phenotyping and data collection. These studies would permit identification of genetic loci for DR susceptibility in the Indian population and should be valuable for better diagnosis and prognosis, and for clinical management of this blinding disease. PMID:26953025

  12. Corneal autofluorescence in presence of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Rovati, Luigi; Docchio, Franco; Azzolini, Claudio; Van Best, Jaap A.

    1998-06-01

    Recently corneal autofluorescence has been proposed as an ocular diagnostic tool for diabetic retinopathy. The method is based on the sensible increase of the natural fluorescence of corneal tissue within specific wavelength in presence of early stage of diabetic retinopathy. The main advantages of this method are that the corneal autofluorescence has been demonstrated to be not age-related and that the cornea is readily accessible to be investigated. In this study 47 insulin-dependent diabetes mellitus and 51 non-insulin- dependent diabetes mellitus patients aged 20 - 90 years have been considered. Patients were selected from the Eye Clinic of S. Raffaele Hospital. The modified Airlie House classification was used to grade the diabetic retinopathy. Corneal autofluorescence has been measured by using both a specifically designed instrument and the Fluorotron Master. Corneal autofluorescence mean value for each diabetic retinopathy measured by using both the instruments correlated with the retinopathy grade.

  13. A cross talk between class A scavenger receptor and receptor for advanced glycation end-products contributes to diabetic retinopathy.

    PubMed

    Ma, Ke; Xu, Yiming; Wang, Chenchen; Li, Nan; Li, Kexue; Zhang, Yan; Li, Xiaoyu; Yang, Qing; Zhang, Hanwen; Zhu, Xudong; Bai, Hui; Ben, Jingjing; Ding, Qingqing; Li, Keran; Jiang, Qin; Xu, Yong; Chen, Qi

    2014-12-15

    In response to hyperglycemia in patients with diabetes, many signaling pathways contribute to the pathogenesis of diabetic complications, including diabetic retinopathy (DR). Excessive production of inflammatory mediators plays an important role in this process. Amadori-glycated albumin, one of the major forms of advanced glycated end-products, has been implicated in DR by inducing inflammatory responses in microglia/macrophages. Our goal was to delineate the potential cross talk between class A scavenger receptor (SR-A) and the receptor for advanced glycated end-product (RAGE) in the context of DR. We show here that SR-A ablation caused an exacerbated form of DR in streptozotocin-injected C57BL/6J mice as evidenced by fundus imaging and electroretinography. Immunohistochemical staining and RT-PCR assay indicated that there was augmented activation of proinflammatory macrophages with upregulated synthesis of proinflammatory mediators in the retina in Sr-a(-/-) mice. Overexpression of SR-A suppressed RAGE-induced mitogen-activated protein kinase (MAPK) signaling, whereas RAGE activation in macrophages favored a proinflammatory (M1) phenotype in the absence of SR-A. Mechanistic analysis on bone marrow-derived macrophages and HEK293 cell line revealed that SR-A interacted with and inhibited the phosphorylation of mitogen-activated protein kinase kinase 7, the major kinase in the RAGE-MAPK-NF-κB signaling, thereby leading to diminished secretion of proinflammatory cytokines. Our findings suggest that the antagonism between SR-A and RAGE contributes to the pathogenesis of DR by nurturing a disease-prone macrophage phenotype. Therefore, specific agonist that boosts SR-A signaling could potentially provide benefits in the prevention and/or intervention of DR. PMID:25352436

  14. Association of vascular endothelial growth factor -634G/C and receptor for advanced glycation end products G82S gene polymorphisms with diabetic retinopathy

    PubMed Central

    Kamal, Asmaa; Abu Eleinen, Khaled; Siam, Ibrahem

    2016-01-01

    AIM To investigate the association of receptor for advanced glycation end products (RAGE) G82S and vascular endothelial growth factor (VEGF) -634 G/C gene polymorphisms with diabetic retinopathy (DR). METHODS Our cross-sectional study included 61 diabetic patients, 12 of them had proliferative diabetic retinopathy (PDR), 15 had non proliferative diabetic retinopathy (NPDR), 34 had no diabetic retinopathy (NDR) and 61 healthy controls. Participants were tested for RAGE G82S and VEGF -634 G/C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. RESULTS We found a significant association between VEGF -634 G/C polymorphism and PDR as PDR patients had increased incidence of VEGF -634 CC genotype compared to NDR patients [odds ratio for CC vs (GC+GG)=6.5, 95% CI=1.5-27.8, P=0.021]. Also VEGF -634 CC genotype and C allele were significantly higher in the PDR than in NPDR patients, which is a novel finding in our study (P=0.024, 0.009 respectively). The mean triglycerides level was significantly higher in diabetic patients with CC genotype (P=0.01) as compared to patients with other genotypes. All cases and control subjects were of the same heterozygous RAGE 82G/S genotype. CONCLUSION Patients carrying VEGF -634 C polymorphism have a higher risk of PDR development, so VEGF -634 G/C polymorphism could be used as a predictive marker for PDR in diabetic patients. We could not find a significant association between RAGE G82S polymorphism and DR. PMID:27588263

  15. Living with Diabetic Retinopathy

    MedlinePlus Videos and Cool Tools

    Announcer: Frances has partial sight as a result of her diabetes but she didn't let that slow her down. She still begins each morning with a ... the air. With this, I can use that as a guide. In fact, I have it on ...

  16. Diaretinopathy database –A Gene database for diabetic retinopathy

    PubMed Central

    Vidhya, Gopalakrishnan; Anusha, Bhaskar

    2014-01-01

    Diabetic retinopathy, is a microvascular complication of diabetes mellitus and is a major cause of adult blindness. Despite advances in diagnosis and treatment the pathogenesis of diabetic retinopathy is not well understood. Results from epidemiological studies of diabetic patients suggest that there are familial predispositions to diabetes and to diabetic retinopathy. Therefore the main purpose of this database is to help both scientists and doctors in studying the candidate genes responsible for causing diabetic retinopathy. For each candidate gene official symbol, chromosome map, number of exons, GT-AG introns, motif, polymorphic variation and 3D structure are given respectively. In addition to molecular class and function of these genes, this database also provides links to download the corresponding nucleotide and amino acid sequences in FASTA format which may be further used for computational approaches. Therefore this database will increase the understanding of the genetics underlying the development or progression of diabetic retinopathy and will have an impact on future diagnostic, prevention and intervention strategies. Availability The database is freely available at http: diaretinopathydatabase.com PMID:24966527

  17. Increased blood viscosity in diabetic proliferative retinopathy.

    PubMed

    Lowe, G D; Ghafour, I M; Belch, J J; Forbes, C D; Foulds, W S; MacCuish, A C

    1986-02-01

    Blood rheology and haemostasis were assessed in 18 diabetics with proliferative retinopathy and in 18 diabetics without proliferative retinopathy, matched for age, sex, smoking habit and type, duration and treatment of diabetes. Proliferative retinopathy was associated with significantly higher levels of blood viscosity at high and low shear rates, which were related to higher levels of plasma viscosity and fibrinogen. Blood urea, glucose, glycosylated haemoglobin and white cell count were also significantly higher, whereas haematocrit, red cell deformability and several other haematological and biochemical variables did not differ significantly in the 2 groups. In view of these findings, and of our recent demonstration that increased blood viscosity also exists in those patients with retinal vein occlusion who develop a similar proliferative retinopathy, we suggest that hyperviscosity may contribute to retinal ischaemia and hence proliferative retinopathy. PMID:3698481

  18. Aspirin in diabetic retinopathy. A systematic review.

    PubMed

    Bergerhoff, Karla; Clar, Christine; Richter, Bernd

    2002-09-01

    Diabetes mellitus is a risk factor for eye disease that can lead to blindness. There have been both concerns that aspirin use might worsen diabetic retinopathy, as well as hopes that aspirin might be beneficial in treating it. We investigated whether there are beneficial effects of aspirin alone and in combination with other antiplatelet agents in the treatment of diabetic retinopathy, and the relative hazards for the development of high-risk proliferative retinopathy following aspirin treatment. We conducted a sensitive search for randomized controlled trials combined with index terms for identifying studies on aspirin treatment in diabetic retinopathy in the Cochrane Library (issue 4, 2001) and Medline (1966 to October, 2001). We examined randomized controlled clinical trials in diabetic patients with (non) proliferative diabetic retinopathy and aspirin treatment alone or in combination with dipyramidole versus placebo administration. Two independent reviewers judged trial eligibility, collected details of study population, interventions, and outcomes using a standard data extraction form. One reviewer assessed the quality of trial reporting. We identified six publications pertinent to our objective. Aspirin dosages ranged from 650 mg to 990 mg daily, the dose of dipyridamole, used in only one trial, was 225 mg per day. Studies lasted 8 weeks to 5 years. All trials showed that aspirin alone or in combination with dipyridamole neither lowered nor increased the risk of the development of diabetic retinopathy. The results suggest that there are no ocular contraindications to taking aspirin if required as part of a treatment for cardiovascular diseases or other medical indications. PMID:12227131

  19. Automated static perimetry to evaluate diabetic retinopathy.

    PubMed Central

    Federman, J L; Lloyd, J

    1984-01-01

    The Octopus automated static perimeter was used to evaluate patients with early diabetic retinopathy. It showed islands of threshold sensitivity depression that were equal to areas of nonperfusion seen on fluorescein angiography. The geographic area of the fundus at risk of developing these field defects was found to be between 20 and 45 degrees, representing the central area of the midperiphery. This procedure has potential as an excellent screening test for early diabetic retinopathy. Images FIGURE 1 (Cont'd) C PMID:6549516

  20. The Adenosinergic System in Diabetic Retinopathy

    PubMed Central

    Vindeirinho, J.; Santiago, A. R.; Cavadas, C.; Ambrósio, A. F.; Santos, P. F.

    2016-01-01

    The neurodegenerative and inflammatory environment that is prevalent in the diabetic eye is a key player in the development and progression of diabetic retinopathy. The adenosinergic system is widely regarded as a significant modulator of neurotransmission and the inflammatory response, through the actions of the four types of adenosine receptors (A1R, A2AR, A2BR, and A3R), and thus could be revealed as a potential player in the events unfolding in the early stages of diabetic retinopathy. Herein, we review the studies that explore the impact of diabetic conditions on the retinal adenosinergic system, as well as the role of the said system in ameliorating or exacerbating those conditions. The experimental results described suggest that this system is heavily affected by diabetic conditions and that the modulation of its components could reveal potential therapeutic targets for the treatment of diabetic retinopathy, particularly in the early stages of the disease. PMID:27034960

  1. New Therapeutic Approaches in Diabetic Retinopathy.

    PubMed

    Vaziri, Kamyar; Schwartz, Stephen G; Relhan, Nidhi; Kishor, Krishna S; Flynn, Harry W

    2015-01-01

    Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. PMID:26676668

  2. Contemporary retinal imaging techniques in diabetic retinopathy: a review.

    PubMed

    Cole, Emily Dawn; Novais, Eduardo Amorim; Louzada, Ricardo Noguera; Waheed, Nadia K

    2016-05-01

    Over the last decade, there has been an expansion of imaging modalities available to clinicians to diagnose and monitor the treatment and progression of diabetic retinopathy. Recently, advances in image technologies related to OCT and OCT angiography have enabled improved visualization and understanding of this disease. In this review, we will describe the use of imaging techniques such as colour fundus photography, fundus autofluorescence, fluorescein angiography, infrared reflectance imaging, OCT, OCT-Angiography and techniques in adaptive optics and hyperspectral imaging in the diagnosis and management of diabetic retinopathy. PMID:26841250

  3. [Diabetic Retinopathy and Neuropathy: New in 2015].

    PubMed

    Henzen, Christoph

    2015-06-01

    In 2014 interesting new results were published in the field of diabetic microangiopathy: (1) In tensive treatment of type 1 diabetes for a mean of 6,5 years confers a lifelong reduction of the risk of diabetic retinopathy; (2) although the rates of diabetes-related complication have declined since 1990, the burden of disease persists because the prevalence of diabetes tripled during the same time; (3) subjects with diabetic neuropathy have structural brain changes, i.e. gray matter loss, findings with possible implications for the prognosis; (4) over 80% of type 2 diabetics who consider their feet to be normal have serious foot pathology. PMID:26098239

  4. Using Anti-VEGF in Diabetic Retinopathy

    PubMed Central

    Marashi, Ameen

    2016-01-01

    Vascular endothelium growth factor is the main pathological factor in diabetic retinopathy and diabetic macular edema (DME), Anti-VEGF agents are safe and effective in DME treatment, there are multiple Anti-VEGF agents, choosing between them is essential to individualize treatment for each patient to achieve the optimum results. PMID:27419238

  5. Retinal Imaging Techniques for Diabetic Retinopathy Screening.

    PubMed

    Goh, James Kang Hao; Cheung, Carol Y; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

    2016-03-01

    Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491

  6. Update on genetics and diabetic retinopathy

    PubMed Central

    Hampton, Blake M; Schwartz, Stephen G; Brantley, Milam A; Flynn, Harry W

    2015-01-01

    Clinical risk factors for diabetic retinopathy (DR), such as duration of disease and degree of glucose control, do not adequately predict disease progression in individual patients, suggesting the presence of a genetic component. Multiple smaller studies have investigated genotype–phenotype correlations in genes encoding vascular endothelial growth factor, aldose reductase, the receptor for advanced glycation end products, and many others. In general, reported results have been conflicting, due to factors including small sample sizes, variations in study design, differences in clinical end points, and underlying genetic differences between study groups. At this time, there is no confirmed association with any risk allele reported. As we continue to collect data from additional studies, the role of genetics in DR may become more apparent. PMID:26648684

  7. Eye Conditions in Older Adults: Diabetic Retinopathy.

    PubMed

    Kirsch, Scott; Iroku-Malize, Tochi

    2016-06-01

    Diabetic retinopathy is related to neovascularization of the retina stimulated by an elevated blood glucose level. This can lead to macular edema, vascular hemorrhage, retinal detachment, and neovascular glaucoma. Diabetic retinopathy is a leading cause of blindness in the United States, and is estimated to affect between 28% and 40% of patients older than 40 years. Significant visual deficit from diabetic retinopathy can lead to social isolation of older individuals by limiting driving, the ability to leave the home or remain in the home safely, and the ability to watch television or read. Primary and secondary prevention includes adequate control of A1c levels. Screening is important for early detection of ocular damage and intervention. Retinal benefits of therapy may predict cardiovascular benefits over a longer period. PMID:27348530

  8. Role of N–epsilon- carboxy methyl lysine, advanced glycation end products and reactive oxygen species for the development of nonproliferative and proliferative retinopathy in type 2 diabetes mellitus

    PubMed Central

    Choudhuri, Subhadip; Dutta, Deep; Sen, Aditi; Chowdhury, Imran Hussain; Mitra, Bhaskar; Mondal, Lakshmi Kanta; Saha, Avijit; Bhadhuri, Gautam

    2013-01-01

    Purpose The aim of the present study was to evaluate the collective role of N-epsilon–carboxy methyl lysine (Nε-CML), advanced glycation end-products (AGEs), and reactive oxygen species (ROS) for the development of retinopathy among type 2 diabetic subjects. Methods Seventy type 2 diabetic subjects with nonproliferative diabetic retinopathy (NPDR), 105 subjects with proliferative diabetic retinopathy (PDR), and 102 patients with diabetes but without retinopathy (DNR) were enrolled in this study. In addition, 95 normal individuals without diabetes were enrolled as healthy controls in this study. Serum and vitreous Nε-CML and AGEs were measured by enzyme-linked immunosorbent assay. The peripheral blood mononuclear cell (PBMC) ROS level was measured by flow cytometric analysis. Serum and PBMC total thiols were measured by spectrophotometry. Results Serum AGEs and Nε-CML levels were significantly elevated in subjects with PDR (p<0.0001) and NPDR (p=0.0297 and p<0.0001, respectively) compared to DNR subjects. Further vitreous AGEs and Nε-CML levels were found to be significantly high among PDR subjects compared to the control group (p<0.0001). PBMC ROS production was found to be strikingly high among NPDR (p<0.0001) and PDR (p<0.0001) subjects as compared to the DNR group. Serum and PBMC total thiol levels were remarkably decreased in NPDR (p<0.0001 and p=0.0043, respectively) and PDR (p=0.0108 and p=0.0332 respectively) subjects than those were considered as DNR. Conclusions Our findings suggest that Nε-CML and ROS are the key modulators for the development of nonproliferative retinopathy among poorly controlled type 2 diabetic subjects. Furthermore, AGEs under persistent oxidative stress and the deprived antioxidant state might instigate the pathogenic process of retinopathy from the nonproliferative to the proliferative state. PMID:23378723

  9. Platelet and coagulation factors in proliferative diabetic retinopathy.

    PubMed Central

    Borsey, D Q; Prowse, C V; Gray, R S; Dawes, J; James, K; Elton, R A; Clarke, B F

    1984-01-01

    Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both beta-thromboglobulin and platelet factor 4 in each of the three groups. Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain. PMID:6202721

  10. Diabetic retinopathy: current and new treatment options.

    PubMed

    Giuliari, Gian P

    2012-01-01

    Diabetes mellitus has become a major health concern worldwide and its incidence is projected to increase. Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are considered the most sight-threatening ocular complications in these patients. Pivotal studies, such as the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetic Retinopathy Study (DRS), have established macular and pan-retinal laser as the gold-standard of treatment for these complications. The recent discovery of the vascular endothelial growth factor (VEGF) and its role in the development of proliferative disease, has led to a movement towards treating PDR and DME with anti-angiogenic medications alone or in conjunction with the gold-standard of care. Due to the severity of the diabetic ocular complications and the rising incidence of diabetes worldwide, it is important for the non-ophthalmologist care provider to be informed of the new treatments available for these conditions in an effort to better guide their patients. In this review, I will discuss the importance of these new methods of treatment as well as the significance of systemic glucose control, vitreous surgery and laser photocoagulation. PMID:22352446

  11. The Role of Microglia in Diabetic Retinopathy

    PubMed Central

    Grigsby, Jeffery G.; Cardona, Sandra M.; Pouw, Cindy E.; Muniz, Alberto; Mendiola, Andrew S.; Tsin, Andrew T. C.; Allen, Donald M.; Cardona, Astrid E.

    2014-01-01

    There is growing evidence that chronic inflammation plays a role in both the development and progression of diabetic retinopathy. There is also evidence that molecules produced as a result of hyperglycemia can activate microglia. However the exact contribution of microglia, the resident immune cells of the central nervous system, to retinal tissue damage during diabetes remains unclear. Current data suggest that dysregulated microglial responses are linked to their deleterious effects in several neurological diseases associated with chronic inflammation. As inflammatory cytokines and hyperglycemia disseminate through the diabetic retina, microglia can change to an activated state, increase in number, translocate through the retina, and themselves become the producers of inflammatory and apoptotic molecules or alternatively exert anti-inflammatory effects. In addition, microglial genetic variations may account for some of the individual differences commonly seen in patient's susceptibility to diabetic retinopathy. PMID:25258680

  12. Diabetic Retinopathy: Animal Models, Therapies, and Perspectives

    PubMed Central

    Cai, Xue; McGinnis, James F.

    2016-01-01

    Diabetic retinopathy (DR) is one of the major complications of diabetes. Although great efforts have been made to uncover the mechanisms underlying the pathology of DR, the exact causes of DR remain largely unknown. Because of multifactor involvement in DR etiology, currently no effective therapeutic treatments for DR are available. In this paper, we review the pathology of DR, commonly used animal models, and novel therapeutic approaches. Perspectives and future directions for DR treatment are discussed. PMID:26881246

  13. Diabetic Retinopathy, Superoxide Damage and Antioxidants

    PubMed Central

    Santos, Julia M.; Mohammad, Ghulam; Zhong, Qing; Kowluru, Renu A.

    2011-01-01

    Retinopathy, the leading cause of acquired blindness in young adults, is one of the most feared complications of diabetes, and hyperglycemia is considered as the major trigger for its development. The microvasculature of the retina is constantly bombarded by high glucose, and this insult results in many metabolic, structural and functional changes. Retinal mitochondria become dysfunctional, its DNA is damaged and proteins encoded by its DNA are decreased. The electron transport chain system becomes compromised, further producing superoxide and providing no relief to the retina from a continuous cycle of damage. Although the retina attempts to initiate repair mechanisms by inducing gene expressions of the repair enzymes, their mitochondrial accumulation remains deficient. Understanding the molecular mechanism of mitochondrial damage should help identify therapies to treat/retard this sight threatening complication of diabetes. Our hope is that if the retinal mitochondria are maintained healthy with adjunct therapies, the development and progression of diabetic retinopathy can be inhibited. PMID:20939803

  14. Cell-Based Therapies for Diabetic Retinopathy

    PubMed Central

    Shaw, Lynn C.; Neu, Matthew B.; Grant, Maria B.

    2013-01-01

    Autologous endothelial progenitor cell (EPC) populations represent a novel treatment for therapeutic revascularization and vascular repair for diabetic patients with complications including diabetic retinopathy. Current therapies are applicable to late-stage disease and carry significant side effects, whereas cell-based therapy may provide an alternative by repairing areas of vasodegeneration and reversing ischemia. However, EPCs from diabetic patients with vascular complications are dysfunctional. Moreover, the diabetic environment poses its own challenges and complicates the use of autologous EPCs. Before EPCs become the ideal “cell therapy,” the optimal EPC must be determined, any functional dysfunction must be corrected prior to use, and the diabetic milieu will require modification to accept the EPCs. This review describes the rationale for harnessing the vascular reparative properties of EPCs with emphasis on the molecular and phenotypic nature of healthy EPCs, how diabetes alters them, and novel strategies to improve dysfunctional EPCs. PMID:21611766

  15. Blood pressure control for diabetic retinopathy

    PubMed Central

    Do, Diana V; Wang, Xue; Vedula, Satyanarayana S; Marrone, Michael; Sleilati, Gina; Hawkins, Barbara S; Frank, Robert N

    2015-01-01

    Background Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. Objectives The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes. Search methods We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data. Selection criteria We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo. Data collection and analysis Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial

  16. Surgery for Proliferative Diabetic Retinopathy: New Tips and Tricks

    PubMed Central

    Oellers, Patrick; Mahmoud, Tamer H.

    2016-01-01

    Over the recent years, retina specialists have enjoyed significant improvements in the surgical management of proliferative diabetic retinopathy including improved preoperative planning, vitreoretinal instrumentation and new surgical maneuvers. In this review, we present new tips and tricks such as preoperative pharmacotherapy approaches including pegaptanib injection and biodegradable dexamethasone implantation, bimanual vitrectomy techniques and the concept of mixing small gauges as well as valved cannulas and intraoperative optical coherence tomography. With advanced surgical planning and sophisticated operative maneuvers tailored to the individual patient, excellent outcomes can be achieved even in severe cases of diabetic tractional detachment. PMID:27195092

  17. Effectiveness of panretinal photocoagulation in severe diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Astakhov, Yuri S.; Shadrichev, Fedor Y.; Lisochkina, Alla B.

    1999-02-01

    Diabetic Retinopathy (DR) is one of the most severe complications of diabetes mellitus. In 1994, in St. Petersburg, a new system of ophthalmologic care for diabetic patients was set up. For Russia, this system represents an example of adequate care for subjects with DM, including screening strategies, documentation and education of patients and general ophthalmologists. According to our data, about one half of examined patients had DR, and about 20% of patients were in need of laser treatment. The aim of present study was to evaluate the effectiveness of panretinal photocoagulation (PRP) in cases of severe DR, including advanced nonproliferative DR (preproliferative DR) and proliferative DR. Data concerning 1073 diabetics are included in this study. PRP was performed in 736 cases (1163 eyes). DR stabilization was estimated after one year follow-up PRP enabled preventing severe visual loss in patients with preproliferative DR and proliferative DR. Our system of specialized ophthalmic care for diabetic patients proved to be effective.

  18. Vitamin D Deficiency Is Associated with the Presence and Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

    PubMed

    Alcubierre, Nuria; Valls, Joan; Rubinat, Esther; Cao, Gonzalo; Esquerda, Aureli; Traveset, Alicia; Granado-Casas, Minerva; Jurjo, Carmen; Mauricio, Didac

    2015-01-01

    There is very few evidences on the role of vitamin D in the development of diabetic retinopathy. The aim of the current study was to explore whether there is an association of vitamin D status and diabetic retinopathy in type 2 diabetes. Two groups of patients were selected: 139 and 144 patients with and without retinopathy, respectively, as assessed by an experienced ophthalmologist. Subjects with advanced late diabetic complications were excluded to avoid confounding biases. 25-Hydroxy-vitamin D3 (25(OH)D) concentrations and vitamin D deficiency were associated with the presence of diabetic retinopathy. Additionally, patients with more advanced stages of retinopathy (grades 2-4) had lower concentrations of 25(OH)D and were more frequently vitamin D deficient as compared with patients not carrying this eye complication. In conclusion, our study confirms the association of vitamin D deficiency with the presence and severity of diabetic retinopathy in type 2 diabetes. Further experimental and prospective studies on this issue are clearly warranted. PMID:26078978

  19. Vitamin D Deficiency Is Associated with the Presence and Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus

    PubMed Central

    Alcubierre, Nuria; Valls, Joan; Rubinat, Esther; Cao, Gonzalo; Esquerda, Aureli; Traveset, Alicia; Granado-Casas, Minerva; Jurjo, Carmen

    2015-01-01

    There is very few evidences on the role of vitamin D in the development of diabetic retinopathy. The aim of the current study was to explore whether there is an association of vitamin D status and diabetic retinopathy in type 2 diabetes. Two groups of patients were selected: 139 and 144 patients with and without retinopathy, respectively, as assessed by an experienced ophthalmologist. Subjects with advanced late diabetic complications were excluded to avoid confounding biases. 25-Hydroxy-vitamin D3 (25(OH)D) concentrations and vitamin D deficiency were associated with the presence of diabetic retinopathy. Additionally, patients with more advanced stages of retinopathy (grades 2–4) had lower concentrations of 25(OH)D and were more frequently vitamin D deficient as compared with patients not carrying this eye complication. In conclusion, our study confirms the association of vitamin D deficiency with the presence and severity of diabetic retinopathy in type 2 diabetes. Further experimental and prospective studies on this issue are clearly warranted. PMID:26078978

  20. Diabetic Retinopathy: Vascular and Inflammatory Disease

    PubMed Central

    Semeraro, F.; Cancarini, A.; dell'Omo, R.; Rezzola, S.; Romano, M. R.; Costagliola, C.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted. PMID:26137497

  1. Accuracy of Primary Care Clinicians in Screening for Diabetic Retinopathy Using Single-Image Retinal Photography

    PubMed Central

    Farley, Tillman F.; Mandava, Naresh; Prall, F. Ryan; Carsky, Cece

    2008-01-01

    PURPOSE Diabetic patients with limited access to ophthalmologists have low screening rates for diabetic retinopathy. We evaluated a diabetic retinopathy screening program in a community health center using single images taken with a nonmydriatic retinal camera and primary care clinicians trained to read retinal images. METHODS This study was conducted from 2001 to 2004 in a multisite community health center staffed by family physicians, advanced practice nurses, and physician’s assistants. The clinic serves a primarily low-income, Hispanic population. Clinic clinicians were trained to read the retinal photographs. All images were overread by an ophthalmologist. Patients were referred to eye care specialists for severe diabetic retinopathy, unknown or other abnormality, or inadequate photographs. We analyzed agreement between the clinicians and the ophthalmologist in recognizing diabetic retinopathy and in determining which patients needed referral. We also analyzed overall screening rates based on clinic access to the camera. RESULTS One thousand forty diabetic patients were screened for diabetic retinopathy at the health center. One hundred thirteen (10.9%) were found to have diabetic retinopathy, 46 severe enough to warrant referral to an ophthalmologist. The clinicians failed to refer 35 (10.2%) of the 344 patients the ophthalmologist believed needed referral. Most cases of missed referral were due to failure to recognize an inadequate photograph or for abnormalities other than diabetic retinopathy. Screening rates were better in the clinic with a permanent camera. CONCLUSIONS Primary care clinicians trained to read single images from a retinal camera have acceptable accuracy in screening for diabetic retinopathy. Further training may be necessary to recognize other common abnormalities. PMID:18779547

  2. Evaluation of the Treatment of Diabetic Retinopathy A Research Project

    ERIC Educational Resources Information Center

    Kupfer, Carl

    1973-01-01

    Evaluated is the treatment of diabetic retinopathy (blindness due to ruptured vessels of the retina as a side effect of diabetes), and described is a research project comparing two types of photocoagulation treatment. (DB)

  3. Plasma Metabonomic Profiling of Diabetic Retinopathy.

    PubMed

    Chen, Liyan; Cheng, Ching-Yu; Choi, Hyungwon; Ikram, Mohammad Kamran; Sabanayagam, Charumathi; Tan, Gavin S W; Tian, Dechao; Zhang, Liang; Venkatesan, Gopalakrishnan; Tai, E Shyong; Wang, Jie Jin; Mitchell, Paul; Cheung, Chiu Ming Gemmy; Beuerman, Roger Wilmer; Zhou, Lei; Chan, Eric Chun Yong; Wong, Tien Yin

    2016-04-01

    Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone. A nested population-based case-control metabonomic study was first performed on 40 DR cases and 40 control subjects with diabetes using gas chromatography-mass spectrometry. Eleven metabolites were found to be correlated with DR, and the majority were robust when adjusted for metabolic risk factors and confounding kidney disease. The metabolite markers 2-deoxyribonic acid; 3,4-dihydroxybutyric acid; erythritol; gluconic acid; and ribose were validated in an independent sample set with 40 DR cases, 40 control subjects with diabetes, and 40 individuals without diabetes. DR cases and control subjects with diabetes were matched by HbA1c in the validation set. Activation of the pentose phosphate pathway was identified from the list of DR metabolite markers. The identification of novel metabolite markers for DR provides insights into potential new pathogenic pathways for this microvascular complication and holds translational value in DR risk stratification and the development of new therapeutic measures. PMID:26822086

  4. Decision support system for diabetic retinopathy using discrete wavelet transform.

    PubMed

    Noronha, K; Acharya, U R; Nayak, K P; Kamath, S; Bhandary, S V

    2013-03-01

    Prolonged duration of the diabetes may affect the tiny blood vessels of the retina causing diabetic retinopathy. Routine eye screening of patients with diabetes helps to detect diabetic retinopathy at the early stage. It is very laborious and time-consuming for the doctors to go through many fundus images continuously. Therefore, decision support system for diabetic retinopathy detection can reduce the burden of the ophthalmologists. In this work, we have used discrete wavelet transform and support vector machine classifier for automated detection of normal and diabetic retinopathy classes. The wavelet-based decomposition was performed up to the second level, and eight energy features were extracted. Two energy features from the approximation coefficients of two levels and six energy values from the details in three orientations (horizontal, vertical and diagonal) were evaluated. These features were fed to the support vector machine classifier with various kernel functions (linear, radial basis function, polynomial of orders 2 and 3) to evaluate the highest classification accuracy. We obtained the highest average classification accuracy, sensitivity and specificity of more than 99% with support vector machine classifier (polynomial kernel of order 3) using three discrete wavelet transform features. We have also proposed an integrated index called Diabetic Retinopathy Risk Index using clinically significant wavelet energy features to identify normal and diabetic retinopathy classes using just one number. We believe that this (Diabetic Retinopathy Risk Index) can be used as an adjunct tool by the doctors during the eye screening to cross-check their diagnosis. PMID:23662341

  5. Photocoagulation as treatment of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Sanchez, J.; Fernandez, L.; de Pedraza, Maria L.; Gamella, C.; Santervas, R.

    1992-03-01

    Diabetes Mellitus is a chronic disease that is revealed with a lot of alterations due to factors such as an absolute or relative reduction of the insulin. It is usually accompanied by generalized arteriosclerosis and prepares for certain microvasculares pathologies such as retinopathy, nefropathy, and neuropathy. The first effects of diabetes in the retina seem to act on the capillaries. The functional modifications of the retinal circulation appear before the structural ones. These consist of the blood flux damage and the obligation of the hematorretinal barrier with extravasacy as can be proved in the fluorophotometry of the vitreous humor. Nowadays, medical treatments are more effective and only vitrectomy and photocoagulation are used in diabetic retinopathy. For that, the argon laser and the xenon arch are used. The treatment is usually spread panretine, with coagulation in a grid pattern around the eye, avoiding the macula and other vital structures, and treating the neoformed blood vessels. The rate of grave visual loss in the studies carried out with there techniques was 12 in relation to 28 in the non-treated cases. The most important factors of risk found, were the discal neoformed blood vessels and the hemorrhage of the vitreous humor. Adverse effects were found such as the reduction of visual sharpness and the contrition of the visual field, these are greater in patients treated with the xenon arch than in those treated with the argon laser.

  6. Lipoprotein(a) Serum Levels in Diabetic Patients with Retinopathy

    PubMed Central

    Malaguarnera, Giulia; Gagliano, Caterina; Vacante, Marco; Malaguarnera, Michele; Leonardi, Daniela Giovanna; Motta, Massimo; Drago, Filippo; Avitabile, Teresio

    2013-01-01

    Background. Atherogenic lipoproteins, such as total cholesterol, LDL cholesterol, oxidized low density lipoprotein, and triglycerides, are associated with progression of retinopathy. Aim. To evaluate the relationship between lipoprotein(a) and retinopathy in patients with type 2 diabetes mellitus. Materials and Methods. We enrolled 145 diabetic consecutive patients (82 females, 63 males; mean age 66.8 ± 12 years, mean duration of diabetes 9.4 ± 6.8 years). Presence and severity of retinopathy were evaluated. Serum lipid profile, including Lp(a) level, was assessed. Results. High Lp(a) levels have been observed in 54 (78.3%) subjects and normal levels in 13 (18.85%) subjects as regards diabetic patients with retinopathy. Lp(a) levels were high in 15 subjects (21.75%) and normal in 63 subjects (91.35%) as regards patients without retinopathy. Conclusions. Lp(a) levels are increased in a significant percentage of patients with retinopathy compared to diabetic patients without retinopathy. The impact of Lp(a) levels on diabetic retinopathy needs to be further investigated. PMID:23862162

  7. Endothelial Progenitor Cells in Diabetic Retinopathy

    PubMed Central

    Lois, Noemi; McCarter, Rachel V.; O’Neill, Christina; Medina, Reinhold J.; Stitt, Alan W.

    2014-01-01

    Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40–50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication. PMID:24782825

  8. Current state of care for diabetic retinopathy in India.

    PubMed

    Ramasamy, Kim; Raman, Rajiv; Tandon, Manish

    2013-08-01

    In this article we review the current state of care of diabetic retinopathy in India. We discuss the magnitude of the problem; diabetes, and diabetic retinopathy in India. We highlight the causes of vision loss in diabetic retinopathy. The current level of awareness among general population and physicians is a concern. Current screening strategies practiced in India and the situational analysis of ophthalmologists in India are also reviewed. We review the current management of diabetic macular edema and proliferative diabetic retinopathy. To know the current practice pattern among retinal surgeons in India, a survey was done and the results of the survey are presented. There are few studies in the Indian population which have found some genetic risk and protective factors and a summary of these studies are also presented in this article. PMID:23657764

  9. Current and Next Generation Portable Screening Devices for Diabetic Retinopathy.

    PubMed

    Micheletti, J Morgan; Hendrick, Andrew M; Khan, Farah N; Ziemer, David C; Pasquel, Francisco J

    2016-03-01

    Diabetic retinopathy (DR) is the leading cause of legal blindness in the United States, and with the growing epidemic of diabetes, a global increase in the incidence of DR is inevitable, so it is of utmost importance to identify the most cost-effective tools for DR screening. Emerging technology may provide advancements to offset the burden of care, simplify the process, and provide financially responsible methods to safely and effectively optimize care for patients with diabetes mellitus (DM). We review here currently available technology, both in production and under development, for DR screening. Preliminary results of smartphone-based devices, "all-in-one" devices, and alternative technologies are encouraging, but are largely pending verification of utility when used by nonophthalmic personnel. Further research comparing these devices to current nonportable telemedicine strategies and clinical fundus examination is necessary to validate these techniques and to potentially overcome the poor compliance around the globe of current strategies for DR screening. PMID:26888973

  10. Metanx and Early Stages of Diabetic Retinopathy

    PubMed Central

    Liu, Haitao; Tang, Jie; Lee, Chieh Allen; Kern, Timothy S.

    2015-01-01

    Purpose. l-Methylfolate, pyridoxal 5′-phosphate, and methylcobalamin, individually have been reported to have beneficial effects on diabetes-induced defects. The possibility that combining these therapeutic approaches might have additional benefit led us to investigate the effect of Metanx against development of early stages of diabetic retinopathy in a mouse model. Methods. C57BL/6J mice were made diabetic with streptozotocin, and some were given Metanx (a combination food product) mixed in the food at a dose of 5 mg/kg of body weight. Mice were killed at 2 months and 10 months of study for assessment of retinal function, retinal vascular histopathology, accumulation of albumin in neural retina, and biochemical and physiological abnormalities in retina. Results. Two months of diabetes significantly increased leukostasis within retinal vessels and superoxide generation by the retina. Diabetes also significantly increased expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylation of IκB. Daily consumption of Metanx significantly inhibited all of these abnormalities. Ten months of diabetes significantly increased the degeneration of retinal capillaries and impaired visual function (spatial frequency threshold (SFT) and a parameter of contrast sensitivity) compared to nondiabetic controls. Daily consumption of Metanx for 10 months inhibited impairment of SFT but had no significant beneficial effect on capillary degeneration, pericyte loss, or the estimate of contrast sensitivity. Conclusions. Metanx inhibited a diabetes-induced defect in retinal spatial frequency threshold and inhibited measures of oxidative stress and inflammation. It had no significant effect on contrast sensitivity or retinal capillary degeneration. Nutritional management with Metanx may help inhibit diabetes-induced defects in visual function. PMID:25574044

  11. Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

    PubMed Central

    Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

    2014-01-01

    AIM To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. METHODS We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). RESULTS The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. CONCLUSION Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM. PMID:24790873

  12. Telomere mean length in patients with diabetic retinopathy

    PubMed Central

    Sharma, Rupali; Gupta, Amod; Thungapathra, M.; Bansal, Reema

    2015-01-01

    Telomere regression has been shown to be associated with several complex disorders like diabetes mellitus, cancer, cataract etc. Diabetic retinopathy develops as a complication of chronic hyperglycemia leading to increased oxidative stress that may potentially lead to shortening of telomeres. We sought to determine whether there is any association between telomere mean length (TML) of peripheral blood monocytes with the presence and severity of diabetic retinopathy. The study involved 120 subjects, comprising 27 non-insulin dependent diabetes mellitus (NIDDM) without any diabetic retinopathy (NDR), 45 NIDDM subjects with non-proliferative diabetic retinopathy (NPDR), 12 NIDDM subjects with proliferative diabetic retinopathy (PDR) and 36 healthy controls. Determination of TML of the study subjects was performed by Southern hybridization using telomere probe. Among the biochemical parameters, HBA1c showed a negative correlation with shortened telomeres in the PDR subjects. However, telomere length was positively correlated with high density lipo protein (HDL) in the control subjects. The control group had significantly greater TML as compared to the rest of the groups and the NDR subjects with NPDR and PDR had substantially decreased TML than the NIDDM subjects without retinopathy. PMID:26670612

  13. New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

    PubMed Central

    Park, Young Gun; Roh, Young-Jung

    2016-01-01

    Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results. PMID:26881240

  14. Scanning laser edema index: a reliable tool to correlate with diabetic retinopathy and systemic risk factors?

    PubMed

    Peyman, Mohammadreza; Tajunisah, Iqbal; Loo, Angela; Chuah, Khai Choon; Subrayan, Visvaraja

    2012-01-01

    To correlate Heidelberg Retina Tomograph (HRT) derived macular edema (DME) index with severity of diabetic retinopathy and systemic factors. A total of 300 diabetic patients were recruited for the study for each of them a value for the macular edema index was obtained using the HRT II. Patients' age, gender, duration and type of diabetes mellitus, latest HbA1c result and presence or absence of co-morbid factors (hypertension, ischemic heart disease, nephropathy) were recorded together with the stage of diabetic retinopathy. These were correlated with DME. Out of 300 patients, HRT defined macula edema was seen in 68 patients (22.6%). There is a wider and higher range (95% percentile) of macula edema index in the severe non proliferative diabetic retinopathy (NPDR) group. Independent samples t test showed significant difference between the severe NPDR group and no DR group (p<0.001), mild NPDR group (p<0.05) and moderate NPDR group (p<0.05). A higher macula edema index was also found to have a low degree of correlation with more advanced stages of retinopathy (r=0.310; p<0.001). Also nephropathy showed a strong and significant correlation with DME. Hypertension had moderately significant correlation with DME. This study found no correlation between ischemic heart disease and DME. HRT derived scanning laser edema index is a reliable objective tool to evaluate diabetic retinopathy and systemic risk factors. PMID:22520399

  15. Ocular anti-VEGF therapy for diabetic retinopathy: overview of clinical efficacy and evolving applications.

    PubMed

    Cheung, Ning; Wong, Ian Y; Wong, Tien Y

    2014-04-01

    Ocular anti-vascular endothelial growth factor (VEGF) therapy represents one of the most significant advances in modern medicine. The introduction and widespread use of ocular anti-VEGF therapy for age-related macular degeneration heralded a new era in the treatment of vascular and exudative diseases of the retina. Its expanding indications now include diabetic macular edema and proliferative diabetic retinopathy, two vision-threatening forms of diabetic retinopathy. It is widely anticipated that ocular anti-VEGF therapy could spark a dramatic shift in the treatment paradigm for diabetic retinopathy. However, despite its clear efficacy shown in clinical trials, the dynamic landscape of evolving medical, ethical, and economic issues related to this new treatment suggests significant challenges ahead. In this article, we provide a discussion of this topic as part of this two-part Bench to Clinic narrative. Here, our Clinic contribution provides an overview of the current evidence from clinical trials on anti-VEGF therapy for diabetic retinopathy, and highlights the hopes and fears of this new treatment from clinical and public health standpoints. In the Bench narrative that precedes this contribution, Simó et al. provide an overview of the role of VEGF in the pathogenesis of diabetic retinopathy. PMID:24652721

  16. Serum magnesium levels in patients with diabetic retinopathy

    PubMed Central

    Kundu, Dipankar; Osta, Manish; Mandal, Tridibeswar; Bandyopadhyay, Ujjwal; Ray, Debes; Gautam, Divyendu

    2013-01-01

    Background: Diabetic retinopathy is one of the leading causes of blindness in the world. Hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes. Hypomagnesemia has been linked to poor glycemic control. Many studies have been undergone to find out the precipitated factors of retinopathy such as duration and type of diabetes, hyperglycemia, hypomagnesemia and increased urinary total protein levels. Aim: This study was carried out to study the correlation between serum magnesium levels, glycosylated hemoglobin and urinary total protein levels in diabetic patients with retinopathy. Materials and Methods: The study population comprised of 30 type 2 diabetic patients without retinopathy as Group 2, 30 type 2 diabetic patients with retinopathy as Group 3 in the age group 45-75 years as cases and 60 age and sex matched healthy individuals as controls (Group 1). Determination of Serum Magnesium (photometric xylidyl blue method), glycosylated hemoglobin, Hb1C (IFCC), fasting blood glucose, postprandial blood glucose (glucose oxidase method) and urine total protein (Pyrogallol red method) was carried out. The statistical software SPSS 11.0 and Systat 8.0 were used for the analysis of the data. Results: Hypomagnesemia was observed in cases compared with both Group 2 and Group 3. FBS, PPBS, HbA1c, Urine total protein levels were increased in cases (without retinopathy and with retinopathy) compared with controls. Conclusion: Hypomagnesemia and albuminuria individually or in conjunction serve as indicators for dysglycemia and could be used as marker for the risk of development of diabetic retinopathy. PMID:23633845

  17. Cost-effectiveness of Different Diabetic Retinopathy Screening Modalities.

    PubMed

    Pasquel, Francisco J; Hendrick, Andrew M; Ryan, Martha; Cason, Emily; Ali, Mohammed K; Narayan, K M Venkat

    2016-03-01

    Current screening strategies aimed at detection of diabetic retinopathy (DR) historically have poor compliance, but advancements in technology can enable improved access to care. Nearly 80% of all persons with diabetes live in low- and middle-income countries (LMICs), highlighting the importance of a cost effective screening program. Establishing mechanisms to reach populations with geographic and financial barriers to access is essential to prevent visual disability. Teleretinal programs leverage technology to improve access and reduce cost. The quality of currently employed screening modalities depends on many variables including the instrument used, use of pupillary mydriasis, number of photographic fields, and the qualifications of the photographer and image interpreter. Recent telemedicine and newer technological approaches have been introduced, but data for these technologies is yet limited. We present results of a systematic review of studies evaluating cost-effectiveness of DR screening, and discuss potential relevance for LMICs. PMID:26719134

  18. Diabetic Retinopathy Risk Factors: Plasma Erythropoietin as a Risk Factor for Proliferative Diabetic Retinopathy

    PubMed Central

    Gholamhossein, Yaghoobi; Asghar, Zarban

    2014-01-01

    Purpose The purpose of this study was to evaluate whether any stage of diabetic retinopathy (DR) is associated with levels of plasma erythropoietin and other plasma parameters. Methods It was examined a representative sample of 180 type 2 diabetes patients aged 40 to 79 years. Ophthalmic examination including a funduscopic examination, performed by an experienced ophthalmologist and the retinal finding were classified according to the grading system for diabetic retinopathy of ETDRS (Early Treatment Diabetic Retinopathy Study). It was measured the levels of plasma erythropoietin, cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, fasting blood glucose and hemoglobin A1C (HbA1C) in 88 DR patients and 92 controls without DR. Risk factors correlated with DR were compared between groups. Results The study group of 180 patients included 72 males and 108 females. The mean age of the patients with and without DR was 57.36 ± 8.87 years and 55.33 ± 8.28 years, respectively. Of the 88 patients with DR, only 9 (10%) had proliferative DR and the rest suffered from non-proliferative DR. The mean plasma levels of erythropoietin in proliferative DR group showed a significant difference in comparison to other groups. The mean plasma levels of cholesterol, triglyceride, apolipoproteins A and B, C-reactive protein, and fasting blood glucose were not significantly different in the three groups except for HbA1C. The absolute relative risk (ARR) also showed that erythropoietin was an increasing risk for proliferative DR (ARR, 1.17; 95% confidence interval, 1.060 to 1.420; odds ratio,1.060). Conclusions Of the factors studied, erythropoietin level showed significant increase in proliferative DR group. The stepwise raised in mean plasma erythropoietin level which demonstrates significant correlation with proliferative DR versus remaining two groups, will be an indication of its role in proliferative DR. PMID:25276078

  19. Current Challenges in Diabetic Retinopathy: Are We Really Doing Better?

    PubMed Central

    Lee, Jae Hyuck

    2016-01-01

    Management of diabetic complications has been a worldwide major global health issue for decades. Recent studies from many parts of the world indicate improvement in this area. However, it is unknown if such an improvement is being realized in Koreans. Although there is limited information regarding diabetic retinopathy management among Koreans, recent epidemiologic studies have indicated improved screening rates and less frequent visual impairment among type 2 diabetics. Moreover, results achieved with new diagnostic and treatment modalities aimed to improve diabetic retinopathy management are encouraging for both physicians and patients. PMID:27302714

  20. Homocysteine Serum Levels in Diabetic Patients with Non Proliferative, Proliferative and without Retinopathy

    PubMed Central

    Gagliano, Caterina; Giordano, Maria; Vacante, Marco; Caraci, Filippo; Drago, Filippo; Avitabile, Teresio; Motta, Massimo

    2014-01-01

    Homocysteine has been associated with extracellular matrix changes. The diabetic retinopathy is a neurovascular complication of diabetes mellitus and it is the leading cause of vision loss among working adults worldwide. In this study, we evaluate the role of homocysteine in diabetic retinopathy analyzing the plasma levels of homocysteine in 63 diabetic type 2 patients with nonproliferative retinopathy (NPDR), 62 patients with proliferative diabetic retinopathy (PDR), 50 healthy subjects used as control group, and 75 randomly selected patients. PMID:24877066

  1. Diabetic retinopathy and the associated risk factors in diabetes type 2 patients in Abha, Saudi Arabia

    PubMed Central

    Ahmed, Razia A.; Khalil, Shamsun N.; Al-Qahtani, Mohammad A. A.

    2016-01-01

    Objectives: To assess the proportion and grades of retinopathy and its risk factors in diabetes type 2 patients. Materials and Methods: This was a cross-sectional study of 401 type 2 diabetic patients. A questionnaire and checklist were used to collect the data. Retinopathy was diagnosed and graded by fundus photographs and slit lamp examination. The duration of diabetes, age of patients, age at onset of diabetes, body mass index, hemoglobin A1c level, blood pressure, and complications were noted. Results: The mean age of male and female patients was 54.93 and 54.25 years; 57.6% were males. The mean age of onset and mean duration of diabetes were 43.91 and 13.4 years, respectively. The proportion of retinopathy was 36.4%. Grades of retinopathy were: Mild 57.5%, moderate 19.9%, severe nonproliferative 11%, and proliferative retinopathy 11.6%; 7.2% of patients had maculopathy. Retinopathy was significantly associated with older age, younger age at onset, longer duration of disease, poorly controlled blood sugar, hypertension, insulin use; the presence of neuropathy and nephropathy appeared as a significant risk. Younger age at onset, longer duration, and insulin use appeared as the strongest predictors for diabetic retinopathy. Conclusions: More than a third (36.4%) of the diabetic patients attending a diabetic center had retinopathy. The control of the risk factors may reduce both prevalence and consequences of retinopathy. PMID:26929725

  2. DREAM: diabetic retinopathy analysis using machine learning.

    PubMed

    Roychowdhury, Sohini; Koozekanani, Dara D; Parhi, Keshab K

    2014-09-01

    This paper presents a computer-aided screening system (DREAM) that analyzes fundus images with varying illumination and fields of view, and generates a severity grade for diabetic retinopathy (DR) using machine learning. Classifiers such as the Gaussian Mixture model (GMM), k-nearest neighbor (kNN), support vector machine (SVM), and AdaBoost are analyzed for classifying retinopathy lesions from nonlesions. GMM and kNN classifiers are found to be the best classifiers for bright and red lesion classification, respectively. A main contribution of this paper is the reduction in the number of features used for lesion classification by feature ranking using Adaboost where 30 top features are selected out of 78. A novel two-step hierarchical classification approach is proposed where the nonlesions or false positives are rejected in the first step. In the second step, the bright lesions are classified as hard exudates and cotton wool spots, and the red lesions are classified as hemorrhages and micro-aneurysms. This lesion classification problem deals with unbalanced datasets and SVM or combination classifiers derived from SVM using the Dempster-Shafer theory are found to incur more classification error than the GMM and kNN classifiers due to the data imbalance. The DR severity grading system is tested on 1200 images from the publicly available MESSIDOR dataset. The DREAM system achieves 100% sensitivity, 53.16% specificity, and 0.904 AUC, compared to the best reported 96% sensitivity, 51% specificity, and 0.875 AUC, for classifying images as with or without DR. The feature reduction further reduces the average computation time for DR severity per image from 59.54 to 3.46 s. PMID:25192577

  3. Language barrier and its relationship to diabetes and diabetic retinopathy

    PubMed Central

    2012-01-01

    Background Language barrier is an important determinant of health care access and health. We examined the associations of English proficiency with type-2 diabetes (T2DM) and diabetic retinopathy (DR) in Asian Indians living in Singapore, an urban city where English is the predominant language of communication. Methods This was a population-based, cross-sectional study. T2DM was defined as HbA1c ≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal photographs were graded for the severity of DR including vision-threatening DR (VTDR). Presenting visual impairment (VI) was defined as LogMAR visual acuity > 0.30 in the better-seeing eye. English proficiency at the time of interview was assessed. Results The analyses included 2,289 (72.1%) English-speaking and 885 (27.9%) Tamil- speaking Indians. Tamil-speaking Indians had significantly higher prevalence of T2DM (46.2 vs. 34.7%, p < 0.001) and, among those with diabetes, higher prevalence of DR (36.0 vs. 30.6%, p < 0.001), VTDR (11.0 vs. 6.5%, p < 0.001), and VI (32.4 vs. 14.6%) than English speaking Indians. Oaxaca decomposition analyses showed that the language-related discrepancies (defined as the difference in prevalence between persons speaking different languages) in T2DM, DR, and VTDR could not be fully explained by socioeconomic measures. Conclusions In an English dominant society, Tamil-speaking Indians are more likely to have T2DM and diabetic retinopathy. Social policies and health interventions that address language-related health disparities may help reduce the public health impact of T2DM in societies with heterogeneous populations. PMID:22974298

  4. Serum Lipids and Proliferative Diabetic Retinopathy and Macular Edema in Persons with Long Term Type 1 Diabetes: The Wisconsin Epidemiologic Study of Diabetic Retinopathy

    PubMed Central

    Klein, Barbara E. K.; Myers, Chelsea E.; Howard, Kerri P.; Klein, Ronald

    2014-01-01

    Importance Total serum and high-density lipoprotein cholesterol have been considered risk factors for severe vascular outcomes in persons with type 1 diabetes. Objective Examine the long term relationships between these two serum lipids and the incidence and prevalence of proliferative diabetic retinopathy and macular edema. Design, Setting, and Participants 903 persons with younger-onset type 1 diabetes who participated in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Exposure(s) Serum total and high-density cholesterol and history of statin use over the course of 5 visits spanning approximately 30 years (1984–2014). Main Outcome Measure(s) Prevalence and incidence of proliferative diabetic retinopathy and macular edema. Results A modest association was found for higher levels of high-density lipoprotein cholesterol and decreased prevalence of proliferative diabetic retinopathy (odds ratio per 10 mg/dL 0.87, 95% confidence interval 0.82–0.93), adjusting for duration of diabetes, glycosylated hemoglobin A1c, statin use, and end stage renal disease. While adjusting for covariates, no associations of serum total or high density lipoprotein cholesterol and incident proliferative diabetic retinopathy or macular edema, nor of statin use with decreased incidence of proliferative diabetic retinopathy or macular edema, were identified. Conclusions and Relevance Over the course of long duration diabetes, during a time of changing medical care, there appeared to be little effect of serum lipids or statins on incidence of proliferative diabetic retinopathy and macular edema. PMID:25502808

  5. Color Doppler imaging of the retrobulbar vessels in diabetic retinopathy

    PubMed Central

    Walasik-Szemplińska, Dorota

    2014-01-01

    Diabetes is a metabolic disease characterized by elevated blood glucose level due to impaired insulin secretion and activity. Chronic hyperglycemia leads to functional disorders of numerous organs and to their damage. Vascular lesions belong to the most common late complications of diabetes. Microangiopathic lesions can be found in the eyeball, kidneys and nervous system. Macroangiopathy is associated with coronary and peripheral vessels. Diabetic retinopathy is the most common microangiopathic complication characterized by closure of slight retinal blood vessels and their permeability. Despite intensive research, the pathomechanism that leads to the development and progression of diabetic retinopathy is not fully understood. The examinations used in assessing diabetic retinopathy usually involve imaging of the vessels in the eyeball and the retina. Therefore, the examinations include: fluorescein angiography, optical coherence tomography of the retina, B-mode ultrasound imaging, perimetry and digital retinal photography. There are many papers that discuss the correlations between retrobulbar circulation alterations and progression of diabetic retinopathy based on Doppler sonography. Color Doppler imaging is a non-invasive method enabling measurements of blood flow velocities in small vessels of the eyeball. The most frequently assessed vessels include: the ophthalmic artery, which is the first branch of the internal carotid artery, as well as the central retinal vein and artery, and the posterior ciliary arteries. The analysis of hemodynamic alterations in the retrobulbar vessels may deliver important information concerning circulation in diabetes and help to answer the question whether there is a relation between the progression of diabetic retinopathy and the changes observed in blood flow in the vessels of the eyeball. This paper presents the overview of literature regarding studies on blood flow in the vessels of the eyeball in patients with diabetic

  6. A case study of a patient with diabetic retinopathy.

    PubMed

    Ebrahimi, Mohammad Hossein; Gharibi, Hamed

    2016-01-01

    The patient, in this report, is a 52 years old male driver who had been diagnosed with type 2 diabetes mellitus (T2DM) five years ago without diabetic retinopathy at the baseline. The patient was being monitored for two intervals. It was at the second interval which he was diagnosed with proliferative retinopathy; in fact, the progression rate of retinopathy from its first sign, which occurred at the middle of the first and second interval, to the point at which the patient lost his vision from the left eye occurred within a year. In this work, we introduce a new factor ignored through all the previously conducted studies, namely, type of profession. This factor which contributes to occupational stress plays an important role in the progression of proliferative retinopathy. We speculate that this factor can accelerate the progression of this disease dramatically, even when the other risk factors are not present. PMID:26907970

  7. Diabetic retinopathy: An epidemic at home and around the world

    PubMed Central

    Raman, Rajiv; Gella, Laxmi; Srinivasan, Sangeetha; Sharma, Tarun

    2016-01-01

    Prevention of blindness due to diabetic retinopathy (DR) requires effective screening strategies, for which eye care providers need to know the magnitude of the burden and the risk factors pertinent in their geographical location. It is estimated that around 72 million of the global adult population (around 8.2%) has diabetes and about one-fifth of all adults with diabetes lives in the South-East Asia. In India, around 65 million people have diabetes. As the global prevalence of diabetes increases, so will the number of people with diabetes-related complications, such as DR; nearly one-third of them are likely to develop this complication. This article reviews the present status of diabetes and DR in India, the current situation of DR services and the projections on the load of morbidity associated with retinopathy. The article compiles the Indian studies elucidating the risk factors for DR. PMID:26953027

  8. [National guidelines for treatment of diabetic retinopathy : Second edition of the national guidelines for treatment of diabetic retinopathy].

    PubMed

    Ziemssen, F; Lemmen, K; Bertram, B; Hammes, H P; Agostini, H

    2016-07-01

    The updated German clinical practice guidelines (second edition) describe the consensus recommendations for prevention and treatment of retinal complications secondary to diabetes. According to the updated numbers on epidemiology a further increase of persons affected is expected. The prevalence of diabetic retinopathy is estimated to be 9-16 % in type 2 diabetes and 24-27 % in type 1 diabetes. A prolongation of the screening interval from 1 to 2 years is recommended for those patients with a lower risk of progression, when retinopathy has not already occurred and no increased systemic risk factors are present. Standardized documentation forms are the foundation for improved communication between the disciplines. If diabetic retinopathy is present, control examinations follow the stipulations of the ophthalmologist. The guidelines define scenarios when the use of optical coherence tomography (OCT) is necessary, e. g. diagnosis and follow-up of macular edema. Besides focal and panretinal laser therapy, the efficacy and risks of intravitreal operative pharmacotherapy are discussed. Focal laser coagulation is recommended for therapy of macular edema without foveal involvement and for macular edema with foveal involvement patients should be informed about the effective alternative forms of treatment. Panretinal laser coagulation is recommended for first line treatment of proliferative diabetic retinopathy and is optional for severe non-proliferative retinopathy. PMID:27352282

  9. Telemedicine in diabetic retinopathy: Access to rural India

    PubMed Central

    Das, Taraprasad; Pappuru, Rajeev Reddy

    2016-01-01

    Diabetic retinopathy (DR) is a growing concern in India. The first step in management of DR is timely screening. With 10% prevalence in rural India, 11 million people are likely to have DR by the year 2030. With limited resources and skilled manpower, it will not be possible to have routine eye examination to identify and treat these patients on a regular basis. Telemedicine is a possible answer in these situations where patients could be remotely screened and appropriately advised. With the advent of several technological advances such as low cost hand-held nonmydriatic camera, increased capabilities of the smartphones to take external eye and retinal photographs coupled with improving broadband connectivity; teleophthalmology in the management of DR could be a reality in the not too distant future. PMID:26953029

  10. Current concepts regarding developmental mechanisms in diabetic retinopathy in Taiwan.

    PubMed

    Chen, Shih-Yin; Hsu, Yuan-Man; Lin, Ying-Ju; Huang, Yu-Chuen; Chen, Chao-Jung; Lin, Wei-De; Liao, Wen-Lin; Chen, Yng-Tay; Lin, Wei-Yong; Liu, Yu-Huei; Yang, Jai-Sing; Sheu, Jinn-Chyuan; Tsai, Fuu-Jen

    2016-06-01

    Diabetic retinopathy (DR) is one of the most feared complications of diabetes and is a leading cause of acquired blindness in working adults. The prevalence of undiagnosed diabetes in Taiwan is about 4%, and the annual incidence of T2D (Type 2 Diabetes) in Taiwan is 1.8% following the 1985 WHO criteria. Multiple mechanisms have been shown in T2DR with some signaling pathways, including the polyol pathway, PKC pathway, AGEs pathway, and MAPK pathway. However, the cause of vision loss in diabetic retinopathy is complex and remains incompletely understood. Herein, we try to fully understand the new concepts regarding hyperglycemia-induced biochemical pathways contributing to DR pathophysiology. Our work may be able to provide new strategies for the prevention and treatment of diabetic vascular complications. PMID:27154195

  11. Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology.

    PubMed

    Simó-Servat, Olga; Simó, Rafael; Hernández, Cristina

    2016-01-01

    Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR. PMID:27376090

  12. Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology

    PubMed Central

    Simó-Servat, Olga; Simó, Rafael; Hernández, Cristina

    2016-01-01

    Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR. PMID:27376090

  13. Evaluating a health video on diabetic retinopathy.

    PubMed

    Meyer, Joos; Johnson, Karim; Bowyer, Joshua; Muir, Josephine; Turner, Angus

    2016-04-01

    Issue addressed Indigenous Australians are 14 times more likely than non-Indigenous Australians to develop diabetic retinopathy (DR). Blindness can be prevented in 98% of cases if DR is identified and treated early. While the National Health and Medical Research Council recommend annual screening for Indigenous Australians, screening attendance rates remain low. The objective of this study was to evaluate whether a targeted health promotion intervention improved patient compliance and screening rates. Methods Bad Sugars, Bad Eyes - a culturally appropriate video targeting DR awareness and the importance of screening among Indigenous Australians - was developed at the Lions Eye Institute, Western Australia. The study used a patient questionnaire pre and post viewing of the video, as well as semi-structured interviews with Aboriginal Health Workers, to explore the influence the resource had on patient knowledge and attitudes. Eighty-four participants, currently involved in DR screening programs, were recruited from Aboriginal Medical Services (AMS) and Aboriginal Community Controlled Health Services (ACCHS). Results The video was found to increase patient knowledge about key DR issues as well as alter patient attitudes identified as potential barriers to screening. The areas most affected by the video resource were knowledge of recommended screening intervals, the severity of potential visual complications if DR is left undiagnosed and untreated and that screening is needed even when asymptomatic. Aboriginal Health Workers positively evaluated the video, all rating it as 'very' culturally appropriate, understandable and relatable. Conclusion The findings of this study suggest that Indigenous DR screening attendance rates could be increased through the expanded use of this video. So what? Indigenous DR screening attendance rates remain low, despite annual recommendations by the National Health and Medical Research Council. This gap needs to be addressed. PMID:26855009

  14. Diabetic retinopathy. Screening and prevention of blindness. A doctoral thesis.

    PubMed

    Kristinsson, J K

    1997-01-01

    Diabetic eye disease is a major cause of blindness in the Western World and remains one of the most serious complications of diabetes mellitus. Retinopathy is the ocular complication of diabetes that most often leads to impaired vision. In recent years laser treatment has been introduced that can significantly decrease the likelihood of blindness in diabetic patients, if the eyes are treated at the appropriate stage of the disease. It remains a public health problem to make sure that each patient is treated at the optimal time in the development of the eye disease. Several types of screening programs have been designed throughout the world to meet this problem. We now report on our active screening program for diabetic eye disease and describe the sight and eye condition of the diabetic patients who have been involved in this program. In 1980, regular eye screening for diabetic retinopathy was initiated at Department of Ophthalmology, Landakot Hospital. The number of diabetic patients seen regularly has increased considerably since then, with 70-80% of type 1 diabetic patients in the country participating in the program in 1990, increasing to over 90% in 1994. About a fifth of type 2 diabetics in the country participated in the program in 1990. The patients have undergone annual eye examinations and fundus photography. Laser treatment is administered for proliferative retinopathy and diabetic macular edema according to the Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study criteria. In 1990, we embarked on a cross-sectional study to evaluate the prevalence of retinopathy and visual impairment of the type 1 and type 2 patients participating in our program. At the time of study, 205 insulin-taking patients, with age at diagnosis of less than 30 years, participated in our screening program. Out of those, retinopathy was present in 106 (52%), patients proliferative retinopathy in 26 (13%) and macular edema in 19 (9%). Visual acuity of 196

  15. Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets

    PubMed Central

    Safi, Sher Zaman; Kumar, Selva; Ismail, Ikram Shah Bin

    2014-01-01

    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

  16. Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets.

    PubMed

    Safi, Sher Zaman; Qvist, Rajes; Kumar, Selva; Batumalaie, Kalaivani; Ismail, Ikram Shah Bin

    2014-01-01

    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

  17. Modes of Retinal Cell Death in Diabetic Retinopathy.

    PubMed

    Feenstra, Derrick J; Yego, E Chepchumba; Mohr, Susanne

    2013-10-01

    Cell death seems to be a prominent feature in the progression of diabetic retinopathy. Several retinal cell types have been identified to undergo cell death in a diabetic environment. Most emphasis has been directed towards identifying apoptosis in the diabetic retina. However, new research has established that there are multiple forms of cell death. This review discusses the different modes of cell death and attempts to classify cell death of retinal cells known to die in diabetic retinopathy. Special emphasis is given to apoptosis, necrosis, autophagic cell death, and pyroptosis. It seems that different retinal cell types are dying by diverse types of cell death. Whereas endothelial cells predominantly undergo apoptosis, pericytes might die by apoptosis as well as necrosis. On the other hand, Müller cells are suggested to die by a pyroptotic mechanism. Diabetes leads to significant Müller cell loss at 7 months duration of diabetes in retinas of diabetic mice compared to non-diabetic, which is prevented by the inhibition of the caspase-1/IL-1β (interleukin-1beta) pathway using the IL-1 receptor knockout mouse. Since pyroptosis is characterized by the activation of the caspase-1/IL-1β pathway subsequently leading to cell death, Müller cells seem to be a prime candidate for this form of inflammation-driven cell death. Considering that diabetic retinopathy is now discussed to potentially be a chronic inflammatory disease, pyroptotic cell death might play an important role in disease progression. Understanding mechanisms of cell death will lead to a more targeted approach in the development of new therapies to treat diabetic retinopathy. PMID:24672740

  18. Visual impairment and blindness in type 2 diabetics: Ife-Ijesa diabetic retinopathy study.

    PubMed

    Onakpoya, O H; Kolawole, B A; Adeoye, A O; Adegbehingbe, B O; Laoye, O

    2016-08-01

    Diabetes and blindness are important health issues globally; we determined the prevalence of blindness, diabetic retinopathy, and other eye diseases in Nigerian-type 2 diabetics. A prospective, cross-sectional study was conducted on consenting type 2 diabetic patients who had scheduled comprehensive eye examination including dilated funduscopy with +78DS. Visual status was graded using the WHO criteria. Approval from Institutional Ethics Committee was obtained. Primary outcome measures were the prevalence and causes of blindness as well as prevalence of diabetic retinopathy. Secondary outcome measures were the presence of other eye diseases. Data were analyzed using SPSS version 13. Two hundred and sixty-six eyes of 133 type 2 diabetic patients aged 22-89 years were studied; 69 (51.9 %) were males while 64 (48.1 %) were females. Five (3.8 %) patients were blind while 27 (20.3 %) were visually impaired. Cataract was the leading cause of blindness (60 %) and visual impairment was found in 59.3 %. Diabetic retinopathy was present in 37 (27.8 %) diabetic patients of which 5 (3.8 %) were proliferative. Diabetic macular edema was present in 31 (23.3 %) patients. Severe visual impairment and blindness were commoner in those with diabetic retinopathy. Refractive error 67 (25.2 %), cataract 63 (23.7 %), and chronic glaucoma 44 (16.5 %) were the most prevalent non-diabetic retinopathy eye diseases. High prevalence of blindness, diabetic retinopathy, and other diseases are seen in type 2 diabetics. Health education, early diagnosis as well as treatment of diabetic retinopathy and other diseases will largely alleviate these ocular morbidities. PMID:26537878

  19. The Diabetic Retinopathy Screening Workflow: Potential for Smartphone Imaging.

    PubMed

    Bolster, Nigel M; Giardini, Mario E; Bastawrous, Andrew

    2015-01-01

    Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems' use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound. PMID:26596630

  20. Optical Coherence Tomography Angiography Features of Diabetic Retinopathy

    PubMed Central

    Hwang, Thomas S.; Jia, Yali; Gao, Simon S.; Bailey, Steven T.; Lauer, Andreas K.; Flaxel, Christina J.; Wilson, David J.; Huang, David

    2015-01-01

    Purpose To describe the optical coherence tomography (OCT) angiography features of diabetic retinopathy Methods Using a 70kHz OCT and the split-spectrum amplitude decorrelation angiography (SSADA) algorithm, 6 × 6 mm 3-dimensional angiograms of the macula of 4 patients with diabetic retinopathy were obtained and compared with fluorescein angiography (FA) for features catalogued by the Early Treatment of Diabetic Retinopathy Study. Results OCT angiography detected enlargement and distortion of the foveal avascular zone, retinal capillary dropout, and pruning of arteriolar branches. Areas of capillary loss obscured by fluorescein leakage on FA were more clearly defined on OCT angiography. Some areas of focal leakage on FA that were thought to be microaneurysms were found to be small tufts of neovascularization that extended above the inner limiting membrane. Conclusion OCT angiography does not show leakage, but can better delineate areas of capillary dropout and detect early retinal neovascularization. This new noninvasive angiography technology may be useful for routine surveillance of proliferative and ischemic changes in diabetic retinopathy. PMID:26308529

  1. Diabetic retinopathy: variations in patient therapeutic outcomes and pharmacogenomics

    PubMed Central

    Agarwal, Aniruddha; Soliman, Mohamed K; Sepah, Yasir J; Do, Diana V; Nguyen, Quan Dong

    2014-01-01

    Diabetes and its microvascular complications in patients poses a significant challenge and constitutes a major health problem. When it comes to manifestations in the eye, each case of diabetic retinopathy (DR) is unique, in terms of the phenotype, genotype, and, more importantly, the therapeutic response. It is therefore important to identify factors that distinguish one patient from another. Personalized therapy in DR is a new trend aimed at achieving maximum therapeutic response in patients by identifying genotypic and phenotypic factors that may result in less than optimal response to conventional therapy, and consequently, lead to poorer outcome. With advances in the identification of these genetic markers, such as gene polymorphisms and human leucocyte antigen associations, as well as development of drugs that can target their effects, the future of personalized medicine in DR is promising. In this comprehensive review, data from various studies have been analyzed to present what has been achieved in the field of pharmacogenomics thus far. An insight into future research is also provided. PMID:25548526

  2. Diabetic Retinopathy in Patients with Diabetic Nephropathy: Development and Progression.

    PubMed

    Jeng, Chi-Juei; Hsieh, Yi-Ting; Yang, Chung-May; Yang, Chang-Hao; Lin, Cheng-Li; Wang, I-Jong

    2016-01-01

    The purpose of current study aims to investigate the development and progression of diabetic retinopathy (DR) in patients with diabetic nephropathy (DN) in a nationwide population-based cohort in Taiwan. Newly diagnosed DN patients and age- and sex-matched controls were identified from the Taiwanese Longitudinal Health Insurance Database from 2000 to 2010. We studied the effects of age, sex, hypertension, dyslipidemia, diabetic polyneuropathy (DPN), and medications on the development of nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME) in patients with DN. Cox proportional hazard regression analyses were used to estimate the adjusted hazard ratios (HRs) of the development of DR. Our results show that the adjusted HRs of NPDR and PDR were 5.01 (95% confidence interval (CI) = 4.68-5.37) and 9.7 (95% CI = 8.15-11.5), respectively, in patients with DN as compared with patients in the non-DN cohort. At 5-year follow-up, patients with DN showed an increased HR of NPDR progression to PDR (HR = 2.26, 95% CI = 1.68-3.03), and the major comorbidities were hypertension (HR = 1.23, 95% CI = 1.10-1.38 with NPDR; HR = 1.33, 95% CI = 1.02-1.72 with PDR) and DPN (HR = 2.03, 95% CI = 1.72-2.41 in NPDR; HR = 2.95, 95% CI = 2.16-4.03 in PDR). Dyslipidemia increased the HR of developing NPDR but not PDR or DME. Moreover, DN did not significantly affect DME development (HR = 1.47, 95% CI = 0.87-2.48) or progression (HR = 0.37, 95% CI = 0.11-1.20). We concluded that DN was an independent risk factor for DR development and progression; however, DN did not markedly affect DME development in this study, and the potential association between these disorders requires further investigation. PMID:27564383

  3. Manganese Superoxide Dismutase Gene Polymorphism (V16A) is Associated with Diabetic Retinopathy in Slovene (Caucasians) Type 2 Diabetes Patients

    PubMed Central

    Petrovič, Mojca Globočnik; Cilenšek, Ines; Petrovič, Daniel

    2008-01-01

    Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy. Two candidate genes that affect the oxidative stress are manganese mitochondrial superoxide dismutase (Mn-SOD) and endothelial nitric oxide synthase (eNOS). The aim of the present study was to examine the role of the V16A polymorphism of the Mn-SOD gene and the 4a/b polymorphism of the eNOS gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. In this cross sectional case-control study 426 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients with diabetic retinopathy and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. A significantly higher frequency of the VV genotype of the V16A polymorphism of the Mn-SOD was found in patients with diabetic retinopathy compared to those without diabetic retinopathy (OR=2.1, 95% CI = 1.2–3.4; p = 0.006), whereas the 4a/b polymorphism of the eNOS gene failed to yield an association with diabetic retinopathy. We may conclude that the VV genotype of the V16A polymorphism of the Mn-SOD gene was associated with diabetic retinopathy in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of diabetic retinopathy in Caucasians. PMID:18057537

  4. [Modern aspects of diabetic retinopathy and diabetic macular oedema treatment].

    PubMed

    Neroev, V V

    2012-01-01

    Main reasons of eyesight deterioration in diabetic patients are diabetic retinopathy (DR) and diabetic macular oedema (DMO). International multicenter studies have shown that retinal laser coagulation in the event of DMO decreases the risk of eyesight loss in 50%, though only in 16% patients it was also possible to improve their eyesight. Use of vascular endothelial growth factor inhibitor--Ranibizumab--have opened a new era in DMA treatment. It's efficacy and safety have been proven in several international studies. This article contains our own data upon the use of Lucentis in patients with DMO. Intravitreal Luzentis injections and subsequent retinal lasercoagulation in the macular zone were performed on 43 eyes; follow up period--6 months. Additional injections were required in 19 cases, average amount of injections--1,4. Mean corrected visual acuity before the treatment was 0,37 +/- 0,06, after 7 days, 1, 3 and 6 months. - respectively 0,41 +/- 0,06, 0,49 +/- 0,06, 0,51 +/- 0,07 and 0,52 +/- 0,07(p<0,05). Mean retina thickness in central zone was 428 +/- 125 mkm before treatment, 391 +/- 24 mkm 7 days after the last injection 349 +/- 23, 313 +/- 21 and 308 +/- 20 mkm (p<0,05) after 1, 3 and 6 months. In addition to that Luzentis use in preoperative period in patients with non-complicated proliferative DR allowed to decrease the risk of hemorrhagic complications. Thereby, intravitreal injections of Luzentis improve functional result of treatment of patients with DMO, increase efficacy and safety of surgical interventions in patients with complicated forms of proliferating DR. PMID:22550713

  5. Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

    PubMed Central

    Gao, Yan; Zhang, Yan; Ru, Yu-Sha; Wang, Xiao-Wu; Yang, Ji-Zhong; Li, Chun-Hui; Wang, Hong-Xing; Li, Xiao-Rong; Li, Bing

    2015-01-01

    AIM To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy (PDR), an advanced stage of diabetic retinopathy (DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy. METHODS Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR (NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I Test, and corneal fluorescein staining. The non-invasive tear film break-up time (NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy. RESULTS The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls (P< 0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls (P < 0.001). Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover, significant decrease in the corneal epithelial density and morphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients. CONCLUSION Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores, and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate

  6. Epidemiology of diabetic retinopathy and maculopathy in Africa: a systematic review

    PubMed Central

    Burgess, P I; MacCormick, I J C; Harding, S P; Bastawrous, A; Beare, N A V; Garner, P

    2013-01-01

    Abstract Aim To summarize findings from studies reporting the prevalence and incidence of diabetic retinopathy and diabetic maculopathy in African countries in light of the rising prevalence of diabetes mellitus. Methods Using a predefined search strategy, we systematically searched MEDLINE, EMBASE, Science Citation index and Conference Proceedings Citation index, African Index Medicus and the grey literature database ‘OpenSIGLE’ for studies published between January 1990 and February 2011. Included studies reported prevalence or incidence of diabetic retinopathy or diabetic maculopathy of subjects with diabetes resident in African countries. Results Sixty-two studies from 21 countries were included: three population-based surveys; two cohort studies; five case–control studies; 32 diabetes clinic-based, nine eye clinic-based and 11 other hospital-based surveys. Included studies varied considerably in terms of patient selection, method of assessing the eye and retinopathy classification. In population-based studies, the reported prevalence range in patients with diabetes for diabetic retinopathy was 30.2 to 31.6%, proliferative diabetic retinopathy 0.9 to 1.3%, and any maculopathy 1.2 to 4.5%. In diabetes clinic-based surveys, the reported prevalence range for diabetic retinopathy was 7.0 to 62.4%, proliferative diabetic retinopathy 0 to 6.9%, and any maculopathy 1.2 to 31.1%. No obvious association between prevalence and income level of the country was detected. Conclusions Large, community-based cross-sectional and cohort studies are needed to investigate rates and determinants of prevalence of diabetic retinopathy, incidence and progression in Africa. Consensus is needed on the most appropriate methods of identification and classification of retinopathy for research and clinical practice. Estimates of prevalence of diabetic retinopathy, proliferative diabetic retinopathy and maculopathy are comparable with recent European and American studies. PMID:22817387

  7. Diabetic retinopathy: retina-specific methods for maintenance of diabetic rodents and evaluation of vascular histopathology and molecular abnormalities

    PubMed Central

    Veenstra, Alexander; Liu, Haitao; Lee, Chieh Allen; Du, Yunpeng; Tang, Jie; Kern, Timothy S.

    2015-01-01

    Diabetic retinopathy is a major cause of visual impairment, which continues to increase in prevalence as more and more people develop diabetes. Despite the importance of vision, the retina is one of the smallest tissues in the body, and specialized techniques to study the retinopathy have been developed. This chapter will summarize several methods used to (i) induce diabetes, (ii) maintain the diabetic animals throughout the months required for the development of typical vascular histopathology, (iii) evaluate vascular histopathology of diabetic retinopathy, and (iv) quantitate abnormalities implicated in the development of the retinopathy. PMID:26331759

  8. Evolving strategies in the management of diabetic retinopathy.

    PubMed

    Abu El-Asrar, Ahmed M

    2013-01-01

    Diabetic retinopathy (DR), the most common long-term complication of diabetes mellitus, remains one of the leading causes of blindness worldwide. Tight glycemic and blood pressure control has been shown to significantly decrease the risk of development as well as the progression of retinopathy and represents the cornerstone of medical management of DR. The two most threatening complications of DR are diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Focal/grid photocoagulation and panretinal photocoagulation are standard treatments for both DME and PDR, respectively. Focal/grid photocoagulation is a better treatment than intravitreal triamcinolone acetonide in eyes with DME. Currently, most experts consider combination focal/grid laser therapy and pharmacotherapy with intravitreal antivascular endothelial growth factor agents in patients with center-involving DME. Combination therapy reduces the frequency of injections needed to control edema. Vitrectomy with removal of the posterior hyaloid seems to be effective in eyes with persistent diffuse DME, particularly in eyes with associated vitreomacular traction. Emerging therapies include fenofibrate, ruboxistaurin, renin-angiotensin system blockers, peroxisome proliferator-activated receptor gamma agonists, pharmacologic vitreolysis, and islet cell transplantation. PMID:24339676

  9. Retinopathy among type 2 diabetic patients seen at a tertiary hospital in Nigeria: a preliminary report

    PubMed Central

    Ashaye, Adeyinka; Arije, Ayodeji; Kuti, Modupe; Olusanya, Bolutife; Ayeni, Ezekiel; Fasanmade, Adesoji; Akinlade, Kehinde; Obajimi, Millicent; Adeleye, Jokotade

    2008-01-01

    Objective To determine the prevalence of diabetic retinopathy among patients attending the diabetic clinics of a tertiary hospital in Nigeria. Methodology We examined the eyes of 76 patients with type 2 diabetes mellitus between July 2003 and January 2004 using dilated fundoscopy at the eye clinic of the University College Hospital, Ibadan. The results were compared with published figures. Results Mean age of patients was 57.5 ± 10.4 years. Thirty–two patients (42.1%) had diabetic retinopathy. Of these, one patient had features of proliferative diabetic retinopathy while the other patients had non-proliferative diabetic retinopathy. Majority (53.1%) of those who had retinopathy had diabetes for more than 10 years, while 21.4% of patients without retinopathy had diabetes for more than 10 years (p = 0.005). The mean serial post-prandial plasma glucose of those who had retinopathy was higher when compared with the mean for those who did not have retinopathy (248.7 mg/dl vs 178.3 mg/dl; p = 0.003). Conclusion The prevalence of diabetic retinopathy in our patients is higher than was previously reported in earlier studies. Patients with diabetes ought to be referred for ophthalmological evaluation and follow-up which they should be actively encouraged to attend. PMID:19668393

  10. Diabetic Retinopathy in Patients with Diabetic Nephropathy: Development and Progression

    PubMed Central

    Jeng, Chi-Juei; Hsieh, Yi-Ting; Yang, Chung-May; Yang, Chang-Hao; Lin, Cheng-Li

    2016-01-01

    The purpose of current study aims to investigate the development and progression of diabetic retinopathy (DR) in patients with diabetic nephropathy (DN) in a nationwide population-based cohort in Taiwan. Newly diagnosed DN patients and age- and sex-matched controls were identified from the Taiwanese Longitudinal Health Insurance Database from 2000 to 2010. We studied the effects of age, sex, hypertension, dyslipidemia, diabetic polyneuropathy (DPN), and medications on the development of nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME) in patients with DN. Cox proportional hazard regression analyses were used to estimate the adjusted hazard ratios (HRs) of the development of DR. Our results show that the adjusted HRs of NPDR and PDR were 5.01 (95% confidence interval (CI) = 4.68–5.37) and 9.7 (95% CI = 8.15–11.5), respectively, in patients with DN as compared with patients in the non-DN cohort. At 5-year follow-up, patients with DN showed an increased HR of NPDR progression to PDR (HR = 2.26, 95% CI = 1.68–3.03), and the major comorbidities were hypertension (HR = 1.23, 95% CI = 1.10–1.38 with NPDR; HR = 1.33, 95% CI = 1.02–1.72 with PDR) and DPN (HR = 2.03, 95% CI = 1.72–2.41 in NPDR; HR = 2.95, 95% CI = 2.16–4.03 in PDR). Dyslipidemia increased the HR of developing NPDR but not PDR or DME. Moreover, DN did not significantly affect DME development (HR = 1.47, 95% CI = 0.87–2.48) or progression (HR = 0.37, 95% CI = 0.11–1.20). We concluded that DN was an independent risk factor for DR development and progression; however, DN did not markedly affect DME development in this study, and the potential association between these disorders requires further investigation. PMID:27564383

  11. PACAP promotes neuron survival in early experimental diabetic retinopathy.

    PubMed

    Szabadfi, Krisztina; Szabo, Aliz; Kiss, Peter; Reglodi, Dora; Setalo, Gyorgy; Kovacs, Krisztina; Tamas, Andrea; Toth, Gabor; Gabriel, Robert

    2014-01-01

    Metabolic changes induced by diabetes lead to a multifactorial progressive disease of the retina with an extremely complex pathogenesis. One of the mechanisms of retinal cell death in diabetes is via apoptosis. Our previous results show that pituitary adenylate cyclase activating polypeptide (PACAP) attenuates the morphological and neurochemical changes in a rat model of diabetic retinopathy. The aim of this study was to investigate the mechanisms of this protective effect. Retinas of streptozotocin-induced diabetic rats were analyzed using apoptosis detection combined with immunolabeling. Western blot was used to measure levels of pro- and anti-apoptotic pathways. Intraocular PACAP injection markedly attenuated diabetic retinal injury: increased levels of the anti-apoptotic p-Akt, p-ERK1, p-ERK2, PKC, Bcl-2, while decreased levels of the pro-apoptotic p-p38MAPK and activated caspases (8, 3, 12) were detected. The number of apoptotic cells increased in all nuclear layers of diabetic retinas, but significantly decreased after PACAP treatment. Our results clearly demonstrate that the protective effects of PACAP are mediated, at least partly, by attenuating apoptosis, including also that of the dopaminergic amacrine cells. Inhibition of apoptosis is one of the PACAP-induced pathways with therapeutic potential in early experimental diabetic retinopathy. PMID:24262293

  12. Retinopathy in youth with type 2 diabetes participating in the TODAY clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the prevalence of retinopathy in 517 youth with type 2 diabetes of 2–8 years duration enrolled in the TODAY study. Retinal photographs were graded centrally for retinopathy using established standards. Retinopathy was identified in 13.7% of subjects. Prev...

  13. An Appraisal of Clinical Practice Guidelines for Diabetic Retinopathy.

    PubMed

    Wu, Connie M; Wu, Annie M; Young, Benjamin K; Wu, Dominic J; Margo, Curtis E; Greenberg, Paul B

    2016-07-01

    The objective is to evaluate the methodological quality of clinical practice guidelines (CPGs) published by the American Academy of Ophthalmology (AAO), Canadian Ophthalmological Society (COS), and Royal College of Ophthalmologists (RCO) for diabetic retinopathy. Four evaluators independently appraised the CPGs using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, which covers 6 domains (Scope and Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, and Editorial Independence). Scores ranged from 35% to 78% (AAO), 60% to 92% (COS), and 35% to 82% (RCO). Intraclass correlation coefficients for the reliability of mean scores were 0.78, 0.78, and 0.79, respectively. The strongest domains were Scope and Purpose, and Clarity of Presentation (COS). The weakest were Stakeholder Involvement (AAO), Rigor of Development (AAO, RCO), Applicability, and Editorial Independence (RCO). Diabetic retinopathy practice guidelines can be improved by targeting Stakeholder Involvement, Rigor of Development, Applicability, and Editorial Independence. PMID:25742906

  14. Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Schweitzer, Dietrich; Deutsch, Lydia; Klemm, Matthias; Jentsch, Susanne; Hammer, Martin; Peters, Sven; Haueisen, Jens; Müller, Ulrich A.; Dawczynski, Jens

    2015-06-01

    The time-resolved autofluorescence of the eye is used for the detection of metabolic alteration in diabetic patients who have no signs of diabetic retinopathy. One eye from 37 phakic and 11 pseudophakic patients with type 2 diabetes, and one eye from 25 phakic and 23 pseudophakic healthy subjects were included in the study. After a three-exponential fit of the decay of autofluorescence, histograms of lifetimes τi, amplitudes αi, and relative contributions Qi were statistically compared between corresponding groups in two spectral channels (490diabetic patients and age-matched controls (p<0.000004). The lack of pixels with a τ2 of ˜360 ps, the increased number of pixels with τ2>450 ps, and the shift of τ3 from ˜3000 to 3700 ps in ch1 of diabetic patients when compared with healthy subjects indicate an increased production of free flavin adenine dinucleotide, accumulation of advanced glycation end products (AGE), and, probably, a change from free to protein-bound reduced nicotinamide adenine dinucleotide at the fundus. AGE also accumulated in the crystalline lens.

  15. Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy.

    PubMed

    Schweitzer, Dietrich; Deutsch, Lydia; Klemm, Matthias; Jentsch, Susanne; Hammer, Martin; Peters, Sven; Haueisen, Jens; Müller, Ulrich A; Dawczynski, Jens

    2015-06-01

    The time-resolved autofluorescence of the eye is used for the detection of metabolic alteration in diabetic patients who have no signs of diabetic retinopathy. One eye from 37 phakic and 11 pseudophakic patients with type 2 diabetes, and one eye from 25 phakic and 23 pseudophakic healthy subjects were included n the study. After a three-exponential fit of the decay of autofluorescence, histograms of lifetimes τ(i), amplitudes α(i), and relative contributions Q(i) were statistically compared between corresponding groups in two spectral channels (490 < ch1 < 560 nm, 560 < ch2 < 700 nm). The change in single fluorophores was estimated by applying the Holm–Bonferroni method and by calculating differences in the sum histograms of lifetimes. Median and mean of the histograms of τ(2), τ(3), and α(3) in ch1 show the greatest differences between phakic diabetic patients and age-matched controls (p < 0.000004). The lack of pixels with a τ(2) of ∼360 ps, the increased number of pixels with τ(2) > 450 ps, and the shift of τ(3) from ∼3000 to 3700 ps in ch1 of diabetic patients when compared with healthy subjects indicate an increased production of free flavin adenine dinucleotide, accumulation of advanced glycation end products (AGE), and, probably, a change from free to protein-bound reduced nicotinamide adenine inucleotide at the fundus. AGE also accumulated in the crystalline lens. PMID:25769278

  16. Screening intervals for diabetic retinopathy and incidence of visual loss: a systematic review.

    PubMed

    Echouffo-Tcheugui, J B; Ali, M K; Roglic, G; Hayward, R A; Narayan, K M

    2013-11-01

    Screening for diabetic retinopathy can help to prevent this complication, but evidence regarding frequency of screening is uncertain. This paper systematically reviews the published literature on the relationship between screening intervals for diabetic retinopathy and the incidence of visual loss. The PubMed and EMBASE databases were searched until December 2012. Twenty five studies fulfilled the inclusion criteria, as these assessed the incidence/prevalence of sight-threatening diabetic retinopathy in relation to screening frequency. The included studies comprised 15 evaluations of real-world screening programmes, three studies modelling the natural history of diabetic retinopathy and seven cost-effectiveness studies. In evaluations of diabetic retinopathy screening programmes, the appropriate screening interval ranged from one to four years, in people with no retinopathy at baseline. Despite study heterogeneity, the overall tendency observed in these programmes was that 2-year screening intervals among people with no diabetic retinopathy at diagnosis were not associated with high incidence of sight-threatening diabetic retinopathy. The modelling studies (non-economic and economic) assessed a range of screening intervals (1-5 years). The aggregated evidence from both the natural history and cost-effectiveness models favors a screening interval >1 year, but ≤2 years. Such an interval would be appropriate, safe and cost-effective for people with no diabetic retinopathy at diagnosis, while screening intervals ≤1 year would be preferable for people with pre-existing diabetic retinopathy. A 2-year screening interval for people with no sight threatening diabetic retinopathy at diagnosis may be safely adopted. For patients with pre-existing diabetic retinopathy, a shorter interval ≤1 year is warranted. PMID:23819487

  17. Fully automated diabetic retinopathy screening using morphological component analysis.

    PubMed

    Imani, Elaheh; Pourreza, Hamid-Reza; Banaee, Touka

    2015-07-01

    Diabetic retinopathy is the major cause of blindness in the world. It has been shown that early diagnosis can play a major role in prevention of visual loss and blindness. This diagnosis can be made through regular screening and timely treatment. Besides, automation of this process can significantly reduce the work of ophthalmologists and alleviate inter and intra observer variability. This paper provides a fully automated diabetic retinopathy screening system with the ability of retinal image quality assessment. The novelty of the proposed method lies in the use of Morphological Component Analysis (MCA) algorithm to discriminate between normal and pathological retinal structures. To this end, first a pre-screening algorithm is used to assess the quality of retinal images. If the quality of the image is not satisfactory, it is examined by an ophthalmologist and must be recaptured if necessary. Otherwise, the image is processed for diabetic retinopathy detection. In this stage, normal and pathological structures of the retinal image are separated by MCA algorithm. Finally, the normal and abnormal retinal images are distinguished by statistical features of the retinal lesions. Our proposed system achieved 92.01% sensitivity and 95.45% specificity on the Messidor dataset which is a remarkable result in comparison with previous work. PMID:25863517

  18. Thioredoxin Interacting Protein (TXNIP) and Pathogenesis of Diabetic Retinopathy

    PubMed Central

    Singh, Lalit P

    2013-01-01

    Chronic hyperglycemia (HG)-associated reactive oxygen/nitrogen species (ROS/RNS) stress and low grade inflammation are considered to play critical roles in the development of diabetic retinopathy (DR). Excess glucose metabolic flux through the aldose reductase/polyol pathway, advanced glycation end product (AGE) formation, elevated hexosamine biosynthesis pathway (HBP), diacyl glycerol/PKC activation, and mitochondrial ROS generation are all implicated in DR. In addition, endoplasmic reticulum stress/unfolded protein response (er-UPR) and deregulation of mitochondrial quality control by autophagy/mitophagy are observed causing cellular bioenergetic deficiency and injury. Recently, a pro-oxidant and pro-apoptotic thioredoxin interacting protein (TXNIP) was shown to be highly upregulated in DR and by HG in retinal cells in culture. TXNIP binds to thioredoxin (Trx) inhibiting its oxidant scavenging and thiolreducing capacity. Hence, prolonged overexpression of TXNIP causes ROS/RNS stress, mitochondrial dysfunction, inflammation and premature cell death in DR. Initially, DR was considered as microvascular complications of endothelial dysfunction and pericyte loss characterized by capillary basement membrane thickening, pericyte ghost, blood retinal barrier leakage, acellular capillary and neovascularization. However, it is currently acknowledged that neuro-glia are also affected by HG in diabetes and that neuronal injury, glial activation, innate immunity/sterile inflammation, and ganglion apoptosis occur early in DR. In addition, retinal pigment epithelium (RPE) becomes dysfunctional in DR. Since TXNIP is induced by HG in most cells, its effects are not restricted to a particular cell type in DR. However, depending on the metabolic activity and anti-oxidant capacity, some cells may be affected earlier by TXNIP than others. Identification of TXNIP sensitive cells and elucidating the underlying mechanism(s) will be critical for preventing pre-mature cell death and

  19. Assessing the Need for Referral in Automatic Diabetic Retinopathy Detection.

    PubMed

    Pires, Ramon; Jelinek, Herbert F; Wainer, Jacques; Goldenstein, Siome; Valle, Eduardo; Rocha, Anderson

    2013-12-01

    Emerging technologies in health care aim at reducing unnecessary visits to medical specialists, minimizing overall cost of treatment and optimizing the number of patients seen by each doctor. This paper explores image recognition for the screening of diabetic retinopathy, a complication of diabetes that can lead to blindness if not discovered in its initial stages. Many previous reports on DR imaging focus on the segmentation of the retinal image, on quality assessment, and on the analysis of presence of DR-related lesions. Although this study has advanced the detection of individual DR lesions from retinal images, the simple presence of any lesion is not enough to decide on the need for referral of a patient. Deciding if a patient should be referred to a doctor is an essential requirement for the deployment of an automated screening tool for rural and remote communities. We introduce an algorithm to make that decision based on the fusion of results by metaclassification. The input of the metaclassifier is the output of several lesion detectors, creating a powerful high-level feature representation for the retinal images. We explore alternatives for the bag-of-visual-words (BoVW)-based lesion detectors, which critically depends on the choices of coding and pooling the low-level local descriptors. The final classification approach achieved an area under the curve of 93.4% using SOFT-MAX BoVW (soft-assignment coding/max pooling), without the need of normalizing the high-level feature vector of scores. PMID:23963192

  20. A systematic review of the association of diabetic retinopathy and cognitive impairment in people with Type 2 diabetes.

    PubMed

    Crosby-Nwaobi, R; Sivaprasad, S; Forbes, A

    2012-05-01

    A systematic review of studies reporting data on the relationship between diabetic eye disease and cognitive impairment in Type 2 diabetes was conducted. The increase in cognitive impairment has mirrored the global increase in diabetes. The aim of the systematic review was to determine the level of association between diabetic retinopathy and cognitive impairment. Item selection, data extraction and critical appraisal were undertaken using standard procedures and independently verified by two researchers. 3 out of 10 potentially relevant studies were included. All studies showed a level of association between diabetic retinopathy and cognitive impairment, suggesting a near threefold increased risk of cognitive impairment in patients with diabetic retinopathy compared to those without. An association of cognitive impairment and severity of diabetic retinopathy was found in males. Diabetic retinopathy was more strongly linked to impairment in the cognitive domains of verbal learning and recent memory. An increased risk of cognitive impairment in patients with diabetic retinopathy was found in the reviewed studies. However, the relationship of severity of diabetic retinopathy and cognitive impairment has not been established. Further studies with standardized measurements for cognitive impairment and diabetic retinopathy are required to delineate this relationship and the role of other factors in this relationship. PMID:22154373

  1. ERK5 Contributes to VEGF Alteration in Diabetic Retinopathy

    PubMed Central

    Wu, Yuexiu; Zuo, Yufeng; Chakrabarti, Rana; Feng, Biao; Chen, Shali; Chakrabarti, Subrata

    2010-01-01

    Diabetic retinopathy is one of the most common causes of blindness in North America. Several signaling mechanisms are activated secondary to hyperglycemia in diabetes, leading to activation of vasoactive factors. We investigated a novel pathway, namely extracellular signal regulated kinase 5 (ERK5) mediated signaling, in modulating glucose-induced vascular endothelial growth factor (VEGF) expression. Human microvascular endothelial cells (HMVEC) were exposed to glucose. In parallel, retinal tissues from streptozotocin-induced diabetic rats were examined after 4 months of follow-up. In HMVECs, glucose caused initial activation followed by deactivation of ERK5 and its downstream mediators myocyte enhancing factor 2C (MEF2C) and Kruppel-like factor 2 (KLF2) mRNA expression. ERK5 inactivation further led to augmented VEGF mRNA expression. Furthermore, siRNA mediated ERK5 gene knockdown suppressed MEF2C and KLF2 expression and increased VEGF expression and angiogenesis. On the other hand, constitutively active MEK5, an activator of ERK5, increased ERK5 activation and ERK5 and KLF2 mRNA expression and attenuated basal- and glucose-induced VEGF mRNA expression. In the retina of diabetic rats, depletion of ERK5, KLF2 and upregulation of VEGF mRNA were demonstrated. These results indicated that ERK5 depletion contributes to glucose induced increased VEGF production and angiogenesis. Hence, ERK5 may be a putative therapeutic target to modulate VEGF expression in diabetic retinopathy. PMID:20671964

  2. Diabetic Retinopathy Is Strongly Predictive of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes

    PubMed Central

    Huang, Chih-Cheng; Lee, Jong-Jer; Lin, Tsu-Kung; Tsai, Nai-Wen; Huang, Chi-Ren; Chen, Shu-Fang; Lu, Cheng-Hsien; Liu, Rue-Tsuan

    2016-01-01

    A well-established, comprehensive, and simple test battery was used here to re-evaluate risk factors for cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. One hundred and seventy-four patients with type 2 diabetes were evaluated through the methods of deep breathing and Valsalva maneuver for correlation with factors that might influence the presence and severity of CAN. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment, and CAN was defined as a CASS score ≥2. Results showed that nephropathy, duration of diabetes, blood pressure, uric acid, and the presence of retinopathy and metabolic syndrome significantly correlated with the CASS score. Age may not be a risk factor for diabetic CAN. However, the effects of diabetes on CAN are more prominent in younger patients than in older ones. Diabetic retinopathy is the most significant risk factor predictive of the presence of CAN in patients with type 2 diabetes. PMID:26955641

  3. Diabetic retinopathy in pregnancy: a population-based study of women with pregestational diabetes.

    PubMed

    Egan, Aoife M; McVicker, Lyle; Heerey, Adrienne; Carmody, Louise; Harney, Fiona; Dunne, Fidelma P

    2015-01-01

    The aim of this observational study was to evaluate screening and progression of diabetic retinopathy during pregnancy in women with pregestational diabetes attending five antenatal centres along the Irish Atlantic seaboard. An adequate frequency of screening was defined as at least two retinal evaluations in separate trimesters. Progression was defined as at least one stage of deterioration of diabetic retinopathy and/or development of diabetic macular edema on at least one eye. Women with pregestational diabetes who delivered after 22 gestational weeks (n = 307) were included. In total, 185 (60.3%) had an adequate number of retinal examinations. Attendance at prepregnancy care was associated with receiving adequate screening (odds ratio 6.23; CI 3.39-11.46 (P < 0.001)). Among those who received adequate evaluations (n = 185), 48 (25.9%) had retinopathy progression. Increasing booking systolic blood pressure (OR 1.03, CI 1.01-1.06, P = 0.02) and greater drop in HbA1c between first and third trimesters of pregnancy (OR 2.05, CI 1.09-3.87, P = 0.03) significantly increased the odds of progression. A significant proportion of women continue to demonstrate retinopathy progression during pregnancy. This study highlights the role of prepregnancy care and the importance of close monitoring during pregnancy and identifies those patients at the highest risk for retinopathy progression. PMID:25945354

  4. Role of microRNAs in the modulation of diabetic retinopathy.

    PubMed

    Mastropasqua, Rodolfo; Toto, Lisa; Cipollone, Francesco; Santovito, Donato; Carpineto, Paolo; Mastropasqua, Leonardo

    2014-11-01

    Diabetic retinopathy (DR) is the leading cause of vision loss in the working-age adults. It affects a third of diabetics. Diabetic macular edema, an advanced complication of DR, develops in nearly 7% of diabetic patients. MicroRNAs (miRNAs) are a novel group of non-coding small RNAs that post-transcriptionally control gene expression by promoting either degradation or translational repression of target messenger RNA. They are implicated in a large variety of physiological and pathophysiological processes, including glucose homeostasis, angiogenesis and modulation of inflammatory response. MiRNAs also play a critical role in the pathogenesis of diabetes and the related micro- and macrovascular complications. The purpose of this review is to describe the potential role of miRNAs in diabetes and evaluate their implication in DR. MiRNAs involved in the modulation of glucose metabolism (insulin secretion and sensitivity) and MiRNAs playing a role in the pathogenesis of DR with their potential target genes are reviewed. Understanding MiRNAs implication in DR could be helpful for developing new gain- or loss- of -function strategies in order to establish effective treatments and reduce the rate of visual disability due to progression of retinopathy. PMID:25128741

  5. Stem cell therapies in the treatment of diabetic retinopathy and keratopathy.

    PubMed

    Kramerov, Andrei A; Ljubimov, Alexander V

    2016-03-01

    Nonproliferative diabetic retinopathy (DR) is characterized by multiple degenerative changes that could be potentially corrected by stem cell therapies. Most studies so far have attempted to alleviate typical abnormalities of early retinopathy, including vascular hyperpermeability, capillary closure and pericyte dropout. Success was reported with adult stem cells (vascular progenitors or adipose stem cells), as well as induced pluripotent stem cells from cord blood. The cells were able to associate with damaged vessels in both pericyte and endothelial lining positions in models of DR and ischemia-reperfusion. In some diabetic models, functional amelioration of vasculature and electroretinograms was noted. Another approach for endogenous progenitor cell therapy is to normalize dysfunctional diabetic bone marrow and residing endothelial progenitors using NO donors, PPAR-δ and -γ agonists, or inhibition of TGF-β. A potentially important strategy would be to reduce neuropathy by stem cell inoculations, either naïve (e.g., paracrine-acting adipose stem cells) or secreting specific neuroprotectants, such as ciliary neurotrophic factor or brain-derived neurotrophic factor that showed benefit in amyotrophic lateral sclerosis and Parkinson's disease. Recent advances in stem cell therapies for diabetic retinal microangiopathy may form the basis of first clinical trials in the near future. Additionally, stem cell therapies may prove beneficial for diabetic corneal disease (diabetic keratopathy) with pronounced epithelial stem cell dysfunction. PMID:26454200

  6. Multispectral fundus imaging for early detection of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Beach, James M.; Tiedeman, James S.; Hopkins, Mark F.; Sabharwal, Yashvinder S.

    1999-04-01

    Functional imaging of the retina and associated structures may provide information for early assessment of risks of developing retinopathy in diabetic patients. Here we show results of retinal oximetry performed using multi-spectral reflectance imaging techniques to assess hemoglobin (Hb) oxygen saturation (OS) in blood vessels of the inner retina and oxygen utilization at the optic nerve in diabetic patients without retinopathy and early disease during experimental hyperglycemia. Retinal images were obtained through a fundus camera and simultaneously recorded at up to four wavelengths using image-splitting modules coupled to a digital camera. Changes in OS in large retinal vessels, in average OS in disk tissue, and in the reduced state of cytochrome oxidase (CO) at the disk were determined from changes in reflectance associated with the oxidation/reduction states of Hb and CO. Step to high sugar lowered venous oxygen saturation to a degree dependent on disease duration. Moderate increase in sugar produced higher levels of reduced CO in both the disk and surrounding tissue without a detectable change in average tissue OS. Results suggest that regulation of retinal blood supply and oxygen consumption are altered by hyperglycemia and that such functional changes are present before clinical signs of retinopathy.

  7. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed Central

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed. PMID:27313539

  8. Spontaneous Closure of a Full-Thickness Macular Hole Associated with Proliferative Diabetic Retinopathy and Persistent Vitreomacular Traction

    PubMed Central

    Reinherz, Benjamin J.; Rubin, Jeffrey S.

    2016-01-01

    Diabetic retinopathy worsens the prognosis of macular holes compared to those of idiopathic etiology. While spontaneous closure of idiopathic macular holes is a well-documented phenomenon, spontaneous closure of macular holes associated with proliferative diabetic retinopathy is rare. We report a case of spontaneous closure of a macular hole associated with proliferative diabetic retinopathy and persistent vitreomacular traction. PMID:27099607

  9. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    PubMed Central

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  10. Vascular endothelial growth factor gene polymorphisms and vitreous proteome changes in diabetic retinopathy.

    PubMed

    Dyer, Kelli H; Silva, Paolo S; Sun, Jennifer K

    2013-01-01

    Ischemic retinal diseases, particularly diabetic retinopathy, continue to significantly impact vision and remain a leading cause of vision loss in working-aged adults. Identifying specific genetic risk factors for ischemic-driven pathways that increase susceptibility to developing diabetic retinopathy is a priority to allow development of accurate risk assessment algorithms, employ earlier intervention, and design novel treatment strategies to reduce the associated visual complications. Single nucleotide polymorphisms (SNPs) in the VEGF gene have been shown to influence the expression of the VEGF protein. Several studies suggest that SNPs in the VEGF gene mediate genetic predisposition to diabetic retinopathy. In addition, alterations in the vitreous proteome, including carbonic anhydrase mediated vascular permeability, have been found to be associated with sight-threatening proliferative diabetic retinopathy and macular edema. Inhibition of these factors could provide new therapeutic opportunities for the treatment of diabetic retinopathy. PMID:24138044

  11. [The management of diabetic retinopathy and diabetic macular edema; joint forces fight for sight].

    PubMed

    Chronopoulos, Argyrios; Roquelaure, Daniel; Jacquier, Paul; Souteyrand, Georges; Matter, Michel; Thumann, Gabriele

    2015-12-16

    Despite the considerable progress in prevention and treatement options since the first big epidemiologic studies in the 80's, diabetic retinopathy still represents the primary cause of blindness in the working age population. The intensified prevention efforts that took place recentyears did show hopeful results as the incidence of diabetic retinopathy seems to decline. However a still considerable number of patients does not meet metabolic or treatment recommandations. In the aftermath of an ongoing globalisation and growing urbanisation of the society, there is an even bigger need of understanding the disease as well as improving prevention and treatment guidelines. PMID:26852554

  12. Vitrectomy for Proliferative Diabetic Retinopathy Associated with Klinefelter Syndrome

    PubMed Central

    Tajiri, Kensuke; Otsuki, Kohei; Sato, Takaki; Kimura, Daisaku; Kobayashi, Takatoshi; Kida, Teruyo; Sugasawa, Jun; Ikeda, Tsunehiko

    2015-01-01

    Introduction We encountered a patient with Klinefelter syndrome (KS) who experienced poor outcomes after vitrectomy for proliferative diabetic retinopathy (PDR). Case A 44-year-old male with poorly controlled diabetes was diagnosed with KS by chromosome analysis. Ocular findings revealed severe PDR complicated with extensive preretinal hemorrhages and traction retinal detachment in his left eye, and pars plana vitrectomy was subsequently performed for treatment. Results A clotting hemorrhage developed during surgery and proved difficult to control. Due to postoperative bleeding and redetachment, the vitrectomy was repeated. At the second operation, we performed a silicone oil tamponade; however, the retina was redetached under the silicone oil, and the light perception vision ultimately disappeared. Conclusion The patient, despite showing increased blood coagulability due to diabetes, presented severe coagulopathy, likely related to KS. In patients with KS and severe PDR, the potential difficulty of vitrectomy should always be kept in mind. PMID:26955343

  13. Asymmetric severity of diabetic retinopathy in Waardenburg syndrome.

    PubMed

    Kashima, Tomoyuki; Akiyama, Hideo; Kishi, Shoji

    2011-01-01

    A 30-year-old female patient was referred to our institution due to vitreous hemorrhage. Best corrected visual acuity of her right and left eyes at her initial visit was 10/20 and 20/20, respectively. Although hypochromic iris was observed in the superior iris between the 10 and 2 o'clock positions in her right eye, her entire left eye exhibited hypochromic iris. Hypopigmentation of the fundus was seen in the superior part of her right eye. This eye also had a huge neovascularization on the optic disc that was 7 discs in diameter. Conversely, her left fundi showed hypopigmentation of the fundus in the entire region of the left eye, and dot hemorrhages were observed all over the left fundi, although no neovascularization could be seen microscopically. Fluorescein angiography showed a huge neovascularization in the right eye and a tiny neovascularization in the left eye. Gene analysis revealed the presence of the PAX3 gene homeobox domain mutation, which led to her being diagnosed as Waardenburg syndrome type 1. Magnetic resonance angiography showed there was no obstructive region at either of the internal carotid arteries and ophthalmic arteries. The severity of the diabetic retinopathy appeared to be correlated with the degree of hypopigmentation in the posterior fundus. We speculate that hypopigmentation of the fundus in Waardenburg syndrome may be responsible for the reduction in retinal metabolism, which led to a reduction in oxygen consumption and prevented further aggravation of the diabetic retinopathy. Only laser treatments using short wavelengths was effective in this case. While the extinction coefficient for hemoglobin when using green light is higher than when using yellow light, the differences between these wavelengths tend to disappear when oxygenated hemoglobin is present. To the best of the authors' knowledge, this is the first case report of a patient with Waardenburg syndrome and diabetic retinopathy. PMID:22205830

  14. Telemedical diabetic retinopathy screening in Hungary: a pilot programme.

    PubMed

    Szabó, Dorottya; Fiedler, Orsolya; Somogyi, Anikó; Somfai, Gábor Márk; Bíró, Zsolt; Ölvedy, Veronika; Hargitai, Zsófia; Németh, János

    2015-04-01

    Our aim was to introduce the Hungarian pilot telemedical screening program for diabetic retinopathy (DRP) and also to evaluate the efficacy of non-mydriatic fundus photographs. A total of 502 eyes of 251 diabetic patients were photographed with a non-mydriatic digital fundus camera in a tertiary diabetology care center. These three 45°-field images were transmitted to the reading center via Internet, where they were graded by two independent ophthalmologists. After non-mydriatic photography (NM method), 28 patients were also examined in mydriasis by an ophthalmologist (O method) and were also photographed in mydriasis (M method). For the comparison of the three methods the kappa statistic was used. With non-mydriatic imaging of 502 eyes no retinopathy was found in 74.5%, DRP was detected in 15.5%, while 10.1% of the photos were ungradable. The rates of DRP severity levels were: 13.55% mild/moderate non-proliferative, 0.59% severe and 1.39% proliferative DRP. Comparing the results of the gradable non-mydriatic photos by the two independent graders, perfect intergrader agreement was found (k = 1.00). The measure of intermethod agreement between NM and M method was also perfect, with a kappa value of 1.00 (grader A and grader B). Based on the results of the O method, there were no misdiagnosed cases nor with the NM-, neither with the M method. Non-mydriatic cameras could be ideal tools of an extended countrywide retinopathy screening program which may serve to reduce the high prevalence of diabetes-related blindness in Hungary. PMID:25712110

  15. Presumed lipid retinopathy in a diabetic dog.

    PubMed

    Halenda, R.M.; Moore, C.P.

    1998-01-01

    An eight-year-old neutered male diabetic Cardigan Welsh Corgi was presented for bilateral mature cataracts. Phacoemulsification and intraocular lens implantation were performed routinely, and recovery was uneventful for several months except for lipemic aqueous flare which gradually resolved during the postoperative period. Five months following surgery the owner presented the dog for decreased vision. White retinal deposits were visualized ophthalmoscopically. Serum analysis revealed that the dog was concurrently markedly hyperlipemic. The patient's diet was changed from a high- to a low-fat diet, following which diabetes control improved, hyperlipemia resolved, and the retinal deposits decreased markedly in size. The retinal deposits seen ophthalmoscopically are presumed to be lipid based upon their association with marked hyperlipemia, and the concurrent resolution of hyperlipemia and the fundic lesions. PMID:11397228

  16. Telemedicine in diabetic retinopathy: current status and future directions.

    PubMed

    Das, Taraprasad; Raman, Rajiv; Ramasamy, Kim; Rani, Padmaja Kumari

    2015-01-01

    Telemedicine is exchange of medical data by electronic telecommunications technology that allows a patient's medical problems evaluated and monitored by a remotely located physician. Over the years, telemedicine and telescreening have become important components in health care, in both disease detection and treatment. Highly visual and image intensive ophthalmology is uniquely suited for telemedicine. Because of rising disease burden coupled with high opportunity cost in detection, diabetic retinopathy is an ideal ophthalmic disease for telescreening and decision-making. It fits to Wilson and Jungner's all 10 criteria of screening for chronic diseases and the American Telehealth Association's 4 screening categories. PMID:25949074

  17. Clock genes and behavioral responses to light are altered in a mouse model of diabetic retinopathy.

    PubMed

    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M; Bennis, Mohamed; Dkhissi-Benyahya, Ouria

    2014-01-01

    There is increasing evidence that melanopsin-expressing ganglion cells (ipRGCs) are altered in retinal pathologies. Using a streptozotocin-induced (STZ) model of diabetes, we investigated the impact of diabetic retinopathy on non-visual functions by analyzing ipRGCs morphology and light-induced c-Fos and Period 1-2 clock genes in the central clock (SCN). The ability of STZ-diabetic mice to entrain to light was challenged by exposure animals to 1) successive light/dark (LD) cycle of decreasing or increasing light intensities during the light phase and 2) 6-h advance of the LD cycle. Our results show that diabetes induces morphological changes of ipRGCs, including soma swelling and dendritic varicosities, with no reduction in their total number, associated with decreased c-Fos and clock genes induction by light in the SCN at 12 weeks post-onset of diabetes. In addition, STZ-diabetic mice exhibited a reduction of overall locomotor activity, a decrease of circadian sensitivity to light at low intensities, and a delay in the time to re-entrain after a phase advance of the LD cycle. These novel findings demonstrate that diabetes alters clock genes and behavioral responses of the circadian timing system to light and suggest that diabetic patients may show an increased propensity for circadian disturbances, in particular when they are exposed to chronobiological challenges. PMID:25006976

  18. Administration of Danhong Injection to diabetic db/db mice inhibits the development of diabetic retinopathy and nephropathy

    PubMed Central

    Liu, Mengyang; Pan, Quan; Chen, Yuanli; Yang, Xiaoxiao; Zhao, Buchang; Jia, Lifu; Zhu, Yan; Zhang, Boli; Gao, Xiumei; Li, Xiaoju; Han, Jihong; Duan, Yajun

    2015-01-01

    Danhong Injection (DHI), a Chinese medicine for treatment of patients with coronary heart disease, inhibits primary abdominal aortic aneurysms in apoE deficient (apoE−/−) mice. Formation of microaneurysms plays an important role in the development of diabetic retinopathy and nephropathy. It remains unknown if DHI can reduce these diabetic complications. In this study, diabetic db/db mice in two groups were injected with saline and DHI, respectively, for 14 weeks. Blood and tissue samples were collected to determine serum glucose, lipids and tissue structure. DHI reduced diabetes-induced body weight gain, serum cholesterol and glucose levels. In retinas, DHI blocked the shrink of whole retina and retinal sub-layers by inhibiting expression of caspase 3, matrix metalloproteinase 2 (MMP-2) and MMP-9, accumulation of carbohydrate macromolecules and formation of acellular capillaries. DHI improved renal functions by inhibiting mesangial matrix expansion, expression of vascular endothelial growth factor A, fibronectin and advanced glycation end products in kidneys. Mechanistically, DHI induced expression of glucokinase, AMPKα/phosphorylated AMPKα, insulin receptor substrate 1, fibroblast growth factor 21 and peroxisome proliferator-activated γ. Expression of genes responsible for energy expenditure was also activated by DHI. Therefore, DHI inhibits diabetic retinopathy and nephropathy by ameliorating glucose metabolism and demonstrates a potential application in clinics. PMID:26061387

  19. Transcriptome analysis using next generation sequencing reveals molecular signatures of diabetic retinopathy and efficacy of candidate drugs

    PubMed Central

    Rajasimha, Harsha K.; Brooks, Matthew J.; Nellissery, Jacob; Wan, Jun; Qian, Jiang; Kern, Timothy S.; Swaroop, Anand

    2012-01-01

    Purpose To define gene expression changes associated with diabetic retinopathy in a mouse model using next generation sequencing, and to utilize transcriptome signatures to assess molecular pathways by which pharmacological agents inhibit diabetic retinopathy. Methods We applied a high throughput RNA sequencing (RNA-seq) strategy using Illumina GAIIx to characterize the entire retinal transcriptome from nondiabetic and from streptozotocin-treated mice 32 weeks after induction of diabetes. Some of the diabetic mice were treated with inhibitors of receptor for advanced glycation endproducts (RAGE) and p38 mitogen activated protein (MAP) kinase, which have previously been shown to inhibit diabetic retinopathy in rodent models. The transcripts and alternatively spliced variants were determined in all experimental groups. Results Next generation sequencing-based RNA-seq profiles provided comprehensive signatures of transcripts that are altered in early stages of diabetic retinopathy. These transcripts encoded proteins involved in distinct yet physiologically relevant disease-associated pathways such as inflammation, microvasculature formation, apoptosis, glucose metabolism, Wnt signaling, xenobiotic metabolism, and photoreceptor biology. Significant upregulation of crystallin transcripts was observed in diabetic animals, and the diabetes-induced upregulation of these transcripts was inhibited in diabetic animals treated with inhibitors of either RAGE or p38 MAP kinase. These two therapies also showed dissimilar regulation of some subsets of transcripts that included alternatively spliced versions of arrestin, neutral sphingomyelinase activation associated factor (Nsmaf), SH3-domain GRB2-like interacting protein 1 (Sgip1), and axin. Conclusions Diabetes alters many transcripts in the retina, and two therapies that inhibit the vascular pathology similarly inhibit a portion of these changes, pointing to possible molecular mechanisms for their beneficial effects. These

  20. Long-term mortality and retinopathy in type 1 diabetes.

    PubMed

    Grauslund, Jakob

    2010-05-01

    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. PMID:20500731

  1. Mayombian ethnic, vegetables low intake, insulin treatment, diabetic nephropathy and severe diabetic retinopathy are determinants of blindness in diabetic Africans

    PubMed Central

    Moise, Mvitu Muaka; Benjamin, Longo-Mbenza; Enoch, Cibanda Yokobo; Igor, Longo Phemba

    2013-01-01

    AIM To determine the frequency and causes of blindness in diabetic Africans. METHODS The study was a cross-sectional survey carried out among known black diabetics consecutively admitted at the Teaching Hospital, University of Kinshasa, between 2005 and 2007. Examination methods included interviewer-administered structured questionnaire, eye examinations (visual acuity, tonometry, funduscopy), and fasting plasma glycaemia test. RESULTS Of the 227 patients examined, 15.9% had blindness. Univariate analyses showed significant association between female, severity of diabetic retinopathy, Mayombian ethnic group, use of insulin treatment, low intake of vegetables, diabetic nephropathy, open angle glaucoma and blindness in all diabetics. After logistic regression, only diabetic nephropathy, use of insulin treatment, macular oedema, Mayombian ethnic group and vegetables low intake were the independent risk factors of blindness in all diabetics. However, after logistic regression in the sub-group with diabetic retinopathy, only open angle glaucoma and proliferative diabetic retinopathy were the independent determinants of blindness. CONCLUSION The majority of the causes of blindness in these diabetic Africans are avoidable. It is recommended that appropriate diabetes care, nutrition education, periodic eye examination and laser photocoagulation facilities should be provided for treating diabetics in sub-Saharan Africa. PMID:24195057

  2. Multiscale AM-FM Methods for Diabetic Retinopathy Lesion Detection

    PubMed Central

    Murray, Victor; Barriga, Eduardo; Murillo, Sergio; Pattichis, Marios; Davis, Herbert; Russell, Stephen; Abràmoff, Michael; Soliz, Peter

    2010-01-01

    We propose the use of multiscale amplitude-modulation frequency-modulation (AM-FM) methods for discriminating between normal and pathological retinal images. The method presented in this paper is tested using standard images from the Early Treatment Diabetic Retinopathy Study (ETDRS). We use 120 regions of 40×40 pixels containing 4 types of lesions commonly associated with diabetic retinopathy (DR) and two types of normal retinal regions that were manually selected by a trained analyst. The region types included: microaneurysms, exudates, neovascularization on the retina, hemorrhages, normal retinal background, and normal vessels patterns. The cumulative distribution functions of the instantaneous amplitude, the instantaneous frequency magnitude, and the relative instantaneous frequency angle from multiple scales are used as texture features vectors. We use distance metrics between the extracted feature vectors to measure interstructure similarity. Our results demonstrate a statistical differentiation of normal retinal structures and pathological lesions based on AM-FM features. We further demonstrate our AM-FM methodology by applying it to classification of retinal images from the MESSIDOR database. Overall, the proposed methodology shows significant capability for use in automatic DR screening. PMID:20129850

  3. Should we start all patients with diabetic retinopathy on fenofibrates?

    PubMed

    Koshy, Jacob; Koshy, Jency M; Thomas, Satish; Kaur, Gurvinder; Mathew, Thomas

    2013-01-01

    There remains a need for strategies that are effective in preventing diabetic retinopathy (DR) or slowing down its progression, which is safe, well-tolerated, and more effective, have a lower risk profile, easy to perform, have more predictable results with less morbidity than the current regimens. Physicians caring for diabetic patients not only need to maximize glycemic control, but also closely monitor and treat other systemic conditions. The consistency of clinical data from the fenofibrate studies showed consistent beneficial effects with fenofibrate in slowing the progression of DR. They demonstrated significant benefit on micro-vascular (i.e., retinopathy and nephropathy) outcome, possibly independent of lipid levels. Can we combine the effectiveness of the current standard procedures with the prevention and slowing down of progression of DR that fenofibrates can offer? Knowledge of the primary mode of action of fenofibrate will be useful for both physicians and patients in determining how best to use this drug as an adjunct in the management of DR and ultimately facilitating the translation of clinical trial data to clinical practice. PMID:24339680

  4. CHOROIDAL THICKNESS IN PATIENTS WITH DIABETIC RETINOPATHY ANALYZED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    REGATIERI, CAIO V.; BRANCHINI, LAUREN; CARMODY, JILL; FUJIMOTO, JAMES G.; DUKER, JAY S.

    2012-01-01

    Purpose This study was designed to examine choroidal thickness in patients with diabetes using spectral-domain optical coherence tomography. Methods Forty-nine patients (49 eyes) with diabetes and 24 age-matched normal subjects underwent high-definition raster scanning using spectral-domain optical coherence tomography with frame enhancement software. Patients with diabetes were classified into 3 groups: 11 patients with mild or moderate nonproliferative diabetic retinopathy and no macular edema, 18 patients with nonproliferative diabetic retinopathy and diabetic macular edema, and 20 patients with treated proliferative diabetic retinopathy and no diabetic macular edema (treated proliferative diabetic retinopathy). Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-μm intervals up to 2,500 μm temporal and nasal to the fovea. Results Reliable measurements of choroidal thickness were obtainable in 75.3% of eyes examined. Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and thinning again temporally in normal subjects and patients with diabetes. Mean subfoveal choroidal thickness was thinner in patients with diabetic macular edema (63.3 μm, 27.2%, P < 0.05) or treated proliferative diabetic retinopathy (69.6 μm, 30.0%, P < 0.01), compared with normal subjects. There was no difference between nonproliferative diabetic retinopathy and normal subjects. Conclusion Choroidal thickness is altered in diabetes and may be related to the severity of retinopathy. Presence of diabetic macular edema is associated with a significant decrease in the choroidal thickness. PMID:22374157

  5. The effects of pleiotrophin in proliferative diabetic retinopathy.

    PubMed

    Zhu, Xuemei; Bai, Yujing; Yu, Wenzhen; Pan, Chungting; Jin, Enzhong; Song, Dan; Xu, Qiong; Yao, Yuou; Huang, Lvzhen; Tao, Yong; Li, Xiaoxin; Zhao, Mingwei

    2015-01-01

    Pleiotrophin (PTN), a secreted, multifunctional cytokine, is involved in angiogenic, fibrotic and neurodegenerative diseases. However, little is known about its effects on diabetic retinopathy, a neurovascular disease. To investigate the role of PTN in proliferative diabetic retinopathy (PDR), PTN concentration in the vitreous was evaluated in PDR patients and non-diabetic controls. PTN expression was observed in epiretinal membranes from patients. PTN knockdown was performed using small interfering (si)RNA, and the effects on retinal pigment epithelium (RPE) cells and human umbilical vascular endothelia cells (HUVECs) were observed in vitro under hyperglycemic and hypoxic conditions. Cell attachment, proliferation, migration, tube formation, cell cycle, apoptosis, extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, and VEGF levels were studied. The vitreous PTN concentration in PDR patients was higher than that in non-diabetic controls, and PTN was highly expressed in the fibrovascular membranes of PDR patients. Under hyperglycemic and hypoxic conditions, PTN knockdown reduced cell attachment, proliferation, migration, and tube formation and induced cell cycle arrest and apoptosis in vitro. Mechanically, PTN depletion decreased ERK 1/2 phosphorylation. Recombinant PTN up regulated the concentration of VEGF in vitro, which can be attenuated by the ERK 1/2 inhibitor. Taken together, our results implied that elevated PTN in PDR patients might participate in the critical processes of the development of PDR, most likely playing roles in angiogenesis and proliferation, possibly by activating the ERK 1/2 pathway and regulating VEGF secretion. These findings provide new insight into the roles of PTN in PDR and suggest that PTN may become a new target for therapeutic intervention in PDR. PMID:25617851

  6. The Effects of Pleiotrophin in Proliferative Diabetic Retinopathy

    PubMed Central

    Zhu, Xuemei; Bai, Yujing; Yu, Wenzhen; Pan, Chungting; Jin, Enzhong; Song, Dan; Xu, Qiong; Yao, Yuou; Huang, Lvzhen; Tao, Yong; Li, Xiaoxin; Zhao, Mingwei

    2015-01-01

    Pleiotrophin (PTN), a secreted, multifunctional cytokine, is involved in angiogenic, fibrotic and neurodegenerative diseases. However, little is known about its effects on diabetic retinopathy, a neurovascular disease. To investigate the role of PTN in proliferative diabetic retinopathy (PDR), PTN concentration in the vitreous was evaluated in PDR patients and non-diabetic controls. PTN expression was observed in epiretinal membranes from patients. PTN knockdown was performed using small interfering (si)RNA, and the effects on retinal pigment epithelium (RPE) cells and human umbilical vascular endothelia cells (HUVECs) were observed in vitro under hyperglycemic and hypoxic conditions. Cell attachment, proliferation, migration, tube formation, cell cycle, apoptosis, extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, and VEGF levels were studied. The vitreous PTN concentration in PDR patients was higher than that in non-diabetic controls, and PTN was highly expressed in the fibrovascular membranes of PDR patients. Under hyperglycemic and hypoxic conditions, PTN knockdown reduced cell attachment, proliferation, migration, and tube formation and induced cell cycle arrest and apoptosis in vitro. Mechanically, PTN depletion decreased ERK 1/2 phosphorylation. Recombinant PTN up regulated the concentration of VEGF in vitro, which can be attenuated by the ERK 1/2 inhibitor. Taken together, our results implied that elevated PTN in PDR patients might participate in the critical processes of the development of PDR, most likely playing roles in angiogenesis and proliferation, possibly by activating the ERK 1/2 pathway and regulating VEGF secretion. These findings provide new insight into the roles of PTN in PDR and suggest that PTN may become a new target for therapeutic intervention in PDR. PMID:25617851

  7. Development of a screening tool for staging of diabetic retinopathy in fundus images

    NASA Astrophysics Data System (ADS)

    Dhara, Ashis Kumar; Mukhopadhyay, Sudipta; Bency, Mayur Joseph; Rangayyan, Rangaraj M.; Bansal, Reema; Gupta, Amod

    2015-03-01

    Diabetic retinopathy is a condition of the eye of diabetic patients where the retina is damaged because of long-term diabetes. The condition deteriorates towards irreversible blindness in extreme cases of diabetic retinopathy. Hence, early detection of diabetic retinopathy is important to prevent blindness. Regular screening of fundus images of diabetic patients could be helpful in preventing blindness caused by diabetic retinopathy. In this paper, we propose techniques for staging of diabetic retinopathy in fundus images using several shape and texture features computed from detected microaneurysms, exudates, and hemorrhages. The classification accuracy is reported in terms of the area (Az) under the receiver operating characteristic curve using 200 fundus images from the MESSIDOR database. The value of Az for classifying normal images versus mild, moderate, and severe nonproliferative diabetic retinopathy (NPDR) is 0:9106. The value of Az for classification of mild NPDR versus moderate and severe NPDR is 0:8372. The Az value for classification of moderate NPDR and severe NPDR is 0:9750.

  8. Computational Investigation of Pkcβ Inhibitors for the Treatment of Diabetic Retinopathy

    PubMed Central

    Gogula, Susmitha Valli; Divakar, Ch; Satyanarayana, Ch; Kumar, Yedla Phani; Lavanaya, Vadapalli Santhosi

    2013-01-01

    Diabetic Retinopathy (DR) is one of the attenuating complications of diabetes mellitus. The key gene responsible for causing diabetic retinopathy is protein kinase C beta (PKCβ). Protein kinase C is a family of protein kinase enzymes which are involved in controlling the function of other proteins through phosphorylation mechanism and plays a crucial role in signal transduction mechanisms. Among all the PKC isoenzymes, PKCβ could be a significant isoenzyme involved in vascular dysfunction during hyperglycemia. Studies show that oral administration of PKCβ inhibitor Ruboxistaurin (LY333531), decreases vessel permeability and improves retinal condition. Thus compounds that decrease the PKCβ activation would be helpful in the treatment of diabetic retinopathy. The compounds similar to Ruboxistaurin are taken from Super Target database and docking analysis was performed. Maleimide derivative 3 showed highest binding affinities compared to Ruboxistaurin and so we advise that compound may be utilized in the treatment of diabetic retinopathy. PMID:24497733

  9. Computational investigation of pkcβ inhibitors for the treatment of diabetic retinopathy.

    PubMed

    Gogula, Susmitha Valli; Divakar, Ch; Satyanarayana, Ch; Kumar, Yedla Phani; Lavanaya, Vadapalli Santhosi

    2013-01-01

    Diabetic Retinopathy (DR) is one of the attenuating complications of diabetes mellitus. The key gene responsible for causing diabetic retinopathy is protein kinase C beta (PKCβ). Protein kinase C is a family of protein kinase enzymes which are involved in controlling the function of other proteins through phosphorylation mechanism and plays a crucial role in signal transduction mechanisms. Among all the PKC isoenzymes, PKCβ could be a significant isoenzyme involved in vascular dysfunction during hyperglycemia. Studies show that oral administration of PKCβ inhibitor Ruboxistaurin (LY333531), decreases vessel permeability and improves retinal condition. Thus compounds that decrease the PKCβ activation would be helpful in the treatment of diabetic retinopathy. The compounds similar to Ruboxistaurin are taken from Super Target database and docking analysis was performed. Maleimide derivative 3 showed highest binding affinities compared to Ruboxistaurin and so we advise that compound may be utilized in the treatment of diabetic retinopathy. PMID:24497733

  10. [Influence of lasting diabetes and non-adjustable glycosylated haemoglobin on occurrence of retinopathy].

    PubMed

    Alajbegović, Salem; Alajbegović, Azra; Omerović, Jasmina; Musanović, Adnan; Lacić, Elmedin

    2011-02-01

    The aim of this study was to investigate the effect of the duration of diabetes and glycemia on the development of diabetic retinopathy in diabetes types 1 and 2 and the prevalence of retinopathy by sex. It examined 278 diabetics in 1999 and 2004, a questionnaire was used to collect data and results of fasting glucose, HbA1c, glycosuria and ketonurie were recorded. Retinopathy was noted in 80 (28.78%) and 187 (67.27%) patients during 1999 and 2004, respectively (p < 0.001). The number of patients with the nonproliferative and preproliferative (p < 0.001) as well as with proliferative retinopathy (p < 0.01) was significantly higher in 2004 in the comparision with 1999. The average HbA1c in 1999 was 13.02%, whereas in 2004 it was 10.57%. Poor control of diabetes was present during both investigations. PMID:21263395

  11. Gene-gene interaction of erythropoietin gene polymorphisms and diabetic retinopathy in Chinese Han.

    PubMed

    Fan, YanFei; Fu, Yin-Yu; Chen, Zhi; Hu, Yuan-Yuan; Shen, Jie

    2016-08-01

    The aim of this study was to investigate the association of three single nucleotide polymorphisms in the erythropoietin gene polymorphisms with diabetic retinopathy and additional role of gene-gene interaction on diabetic retinopathy risk. A total of 1193 patients (579 men, 614 women) with type 2 diabetes mellitus were selected, including 397 diabetic retinopathy patients and 796 controls (type 2 diabetes mellitus patients without diabetic retinopathy); the mean age of all participants was 56.7 ± 13.9 years. Three single nucleotide polymorphisms were selected: rs507392, rs1617640, and rs551238. The t-test was used for comparison of erythropoietin protein level erythropoietin levels in patients having different erythropoietin genotypes. Logistic regression model was used to examine the association between three single nucleotide polymorphisms and diabetic retinopathy. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the impact of interaction among three single nucleotide polymorphisms on CVD risk. After covariates adjustment, the carriers of homozygous mutant of three single nucleotide polymorphisms have higher diabetic retinopathy risk than those with wild-type homozygotes, OR (95% CI) were 2.04 (1.12-2.35), 1.87 (1.10-2.41) and 1.15 (1.06-1.76), respectively. Generalized multifactor dimensionality reduction model indicated a significant three-locus model (p = 0.0010) involving rs507392, rs1617640, and rs551238. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. Subjects with TC or CC-TG or GG-AC or CC genotype have the highest diabetic retinopathy risk. In conclusion, our results support an important association of rs507392, rs1617640 and rs551238 minor allele of erythropoietin with increased diabetic retinopathy risk, and additional interaction among three single nucleotide polymorphisms. PMID

  12. Laser photocoagulation stops diabetic retinopathy by controlling lactic acid formation

    NASA Astrophysics Data System (ADS)

    Wolbarsht, Myron L.

    1994-08-01

    Many different types of proliferative retinopathy induced by various types of initial disorders have a common pathology in their mid and terminal stages. Thus, proper therapy is devoted toward elimination of the initial cause as well as alleviation of the proliferative processes. Vasodilatation, which is an initial symptom of diabetes, is itself destructive to the retinal capillary bed and appears to be a constant feature in all stages of diabetic retinopathy. In the mid and late stages, the vasodilatation seems very dependent upon capillary dropout, whereas the initial vasodilatation may derive from quite different causes. The efficacy of photocoagulation as a therapy for all stages seems to derive from decreasing the metabolism in the photoreceptor layer sufficiently to result in vasoconstriction of the retinal vessels. A model is proposed to show how diabetes, by altering the metabolism in the photoreceptor layer to produce excess lactic acid, causes the initial vasodilatation. The lactic acid also induces free radical (superoxide) formation; both act together to destroy the retinal capillary bed followed by vasoproliferation. Photocoagulation, thus, is even more appropriate for this particular syndrome than previously had been thought, as it not only reduces potentially destructive vasodilatation but also removes the metabolic cause of the free radical induced destruction of the capillary endothelium which is the initial step in capillary drop-out. A review of the present data indicates that the best type of pan- retinal photocoagulation is a very light type affecting the photoreceptors only with a minimal amount of damage to other parts of retina and the vessels in the choroid. The possible use of photochemical types of destruction of the photoreceptor as a therapeutic modality is attractive, but it is certainly too speculative to use until more detailed investigations have been completed. However, the basic therapeutic approach of choice may be to prevent the

  13. [The German program for disease management guidelines: type 2 diabetes--diabetic retinopathy/maculopathy guideline 2006. Short review].

    PubMed

    Ollenschläger, Günter; Kopp, Ina; Thole, Henning; Lelgemann, Monika

    2007-02-15

    In Germany, the first national consensus between six medical scientific associations on evidence-based recommendations for prevention and therapy of retinopathy/maculopathy in type 2 diabetes was reached in fall 2006. The recommendations' main sources are the NICE Retinopathy Guideline 2002, and existing German guidelines and reviews of recent scientific evidence. The article gives an overview on authors, sources, and key recommendations of the German National Disease Management Guideline Type 2 Diabetes-Retinopathy/Maculopathy 2006 (www.diabetes.versorgungsleitlinien.de). PMID:17323022

  14. Automated retinal image analysis for diabetic retinopathy in telemedicine.

    PubMed

    Sim, Dawn A; Keane, Pearse A; Tufail, Adnan; Egan, Catherine A; Aiello, Lloyd Paul; Silva, Paolo S

    2015-03-01

    There will be an estimated 552 million persons with diabetes globally by the year 2030. Over half of these individuals will develop diabetic retinopathy, representing a nearly insurmountable burden for providing diabetes eye care. Telemedicine programmes have the capability to distribute quality eye care to virtually any location and address the lack of access to ophthalmic services. In most programmes, there is currently a heavy reliance on specially trained retinal image graders, a resource in short supply worldwide. These factors necessitate an image grading automation process to increase the speed of retinal image evaluation while maintaining accuracy and cost effectiveness. Several automatic retinal image analysis systems designed for use in telemedicine have recently become commercially available. Such systems have the potential to substantially improve the manner by which diabetes eye care is delivered by providing automated real-time evaluation to expedite diagnosis and referral if required. Furthermore, integration with electronic medical records may allow a more accurate prognostication for individual patients and may provide predictive modelling of medical risk factors based on broad population data. PMID:25697773

  15. The kallikrein-kinin system in diabetic retinopathy.

    PubMed

    Bhat, Menakshi; Pouliot, Mylène; Couture, Réjean; Vaucher, Elvire

    2014-01-01

    Diabetic retinopathy (DR) is a major microvascular complication associated with type 1 and type 2 diabetes mellitus, which can lead to visual impairment and blindness. Current treatment strategies for DR are mostly limited to laser therapies, steroids, and anti-VEGF agents, which are often associated with unwanted side effects leading to further complications. Recent evidence suggests that kinins play a primary role in the development of DR through enhanced vascular permeability, leukocytes infiltration, and other inflammatory mechanisms. These deleterious effects are mediated by kinin B1 and B2 receptors, which are expressed in diabetic human and rodent retina. Importantly, kinin B1 receptor is virtually absent in sane tissue, yet it is induced and upregulated in diabetic retina. These peptides belong to the kallikrein-kinin system (KKS), which contains two separate and independent pathways of regulated serine proteases, namely plasma kallikrein (PK) and tissue kallikrein (TK) that are involved in the biosynthesis of bradykinin (BK) and kallidin (Lys-BK), respectively. Hence, ocular inhibition of kallikreins or antagonism of kinin receptors offers new therapeutic avenues in the treatment and management of DR. Herein, we present an overview of the principal features and known inflammatory mechanisms associated with DR along with the current therapeutic approaches and put special emphasis on the KKS as a new and promising therapeutic target due to its link with key pathways directly associated with the development of DR. PMID:25130041

  16. Prevalence of diabetic retinopathy in India: The All India Ophthalmological Society Diabetic Retinopathy Eye Screening Study 2014

    PubMed Central

    Gadkari, Salil S; Maskati, Quresh B; Nayak, Barun Kumar

    2016-01-01

    Aim: The aim of this study is to ascertain the prevalence of diabetic retinopathy (DR) in diabetic patients across the nation and attempt to establish history-based risk factors. Materials and Methods: A cross-sectional study of diabetic patients was conducted as an initiative of the All India Ophthalmological Society from 14th November to 21st November 2014. Known diabetics were evaluated voluntarily by members of the society at 194 centers using a structured protocol provided by the society for examination. The results were evaluated to ascertain the prevalence of DR in the population studied and to establish relation with gender, age, and history-based risk factors such as duration of diabetes, insulin use, and other end-organ disease using the Chi-square test. Results: A total of 6218 known diabetics were screened. Totally, 5130 data entry forms were considered suitable for further evaluation. About 61.2% were males, 88.6% were between 40 and 80 years of age, almost two-thirds of the patients were from the west and south zones, and over half had diabetes more than 5 years. The data set was predominantly urban 84.7% and 46.1% had no family history. DR prevalence in the entire data set was 21.7%. Prevalence was more in males (P = 0.007), diabetics more than 5 years (P = 0.001), those above 40 years (P = 0.01), insulin users (P = 0.001), and history of vascular accidents (P = 0.0014). Significantly 22.18% of patients detected with DR had a vision of 6/18 or better in the worse eye. Conclusion: The study reiterated the findings of earlier regional studies on a pan Indian scale and put data in perspective. PMID:26953022

  17. Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives.

    PubMed

    Wu, Ying; Tang, Luosheng; Chen, Baihua

    2014-01-01

    In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR. PMID:25180070

  18. Oxidative Stress: Implications for the Development of Diabetic Retinopathy and Antioxidant Therapeutic Perspectives

    PubMed Central

    Tang, Luosheng; Chen, Baihua

    2014-01-01

    In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR. PMID:25180070

  19. Prevalence of Diabetic Retinopathy in the United States, 2005–2008

    PubMed Central

    Zhang, Xinzhi; Saaddine, Jinan B.; Chou, Chiu-Fang; Cotch, Mary Frances; Cheng, Yiling J.; Geiss, Linda S.; Gregg, Edward W.; Albright, Ann L.; Klein, Barbara E. K.; Klein, Ronald

    2010-01-01

    Context The prevalence of diabetes in the United States has increased. People with diabetes are at risk for diabetic retinopathy. No recent national population-based estimate of the prevalence and severity of diabetic retinopathy exists. Objectives To describe the prevalence and risk factors of diabetic retinopathy among US adults with diabetes aged 40 years and older. Design, Setting, and Participants Analysis of a cross-sectional, nationally representative sample of the National Health and Nutrition Examination Survey 2005–2008 (N=1006). Diabetes was defined as a self-report of a previous diagnosis of the disease (excluding gestational diabetes mellitus) or glycated hemoglobin A1c of 6.5% or greater. Two fundus photographs were taken of each eye with a digital nonmydriatic camera and were graded using the Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence estimates were weighted to represent the civilian, noninstitutionalized US population aged 40 years and older. Main Outcome Measurements Diabetic retinopathy and vision-threatening diabetic retinopathy. Results The estimated prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was 28.5% (95% confidence interval [CI], 24.9%–32.5%) and 4.4% (95% CI, 3.5%–5.7%) among US adults with diabetes, respectively. Diabetic retinopathy was slightly more prevalent among men than women with diabetes (31.6%; 95% CI, 26.8%–36.8%; vs 25.7%; 95% CI, 21.7%–30.1%; P=.04). Non-Hispanic black individuals had a higher crude prevalence than non-Hispanic white individuals of diabetic retinopathy (38.8%; 95% CI, 31.9%–46.1%; vs 26.4%; 95% CI, 21.4%–32.2%; P=.01) and vision-threatening diabetic retinopathy (9.3%; 95% CI, 5.9%–14.4%; vs 3.2%; 95% CI, 2.0%–5.1%; P=.01). Male sex was independently associated with the presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% CI, 1.39–3.10), as well as higher hemoglobin A1c level (OR

  20. Validation of Smartphone Based Retinal Photography for Diabetic Retinopathy Screening

    PubMed Central

    Rajalakshmi, Ramachandran; Arulmalar, Subramanian; Usha, Manoharan; Prathiba, Vijayaraghavan; Kareemuddin, Khaji Syed; Anjana, Ranjit Mohan; Mohan, Viswanathan

    2015-01-01

    Aim To evaluate the sensitivity and specificity of “fundus on phone’ (FOP) camera, a smartphone based retinal imaging system, as a screening tool for diabetic retinopathy (DR) detection and DR severity in comparison with 7-standard field digital retinal photography. Design Single-site, prospective, comparative, instrument validation study. Methods 301 patients (602 eyes) with type 2 diabetes underwent standard seven-field digital fundus photography with both Carl Zeiss fundus camera and indigenous FOP at a tertiary care diabetes centre in South India. Grading of DR was performed by two independent retina specialists using modified Early Treatment of Diabetic Retinopathy Study grading system. Sight threatening DR (STDR) was defined by the presence of proliferative DR(PDR) or diabetic macular edema. The sensitivity, specificity and image quality were assessed. Results The mean age of the participants was 53.5 ±9.6 years and mean duration of diabetes 12.5±7.3 years. The Zeiss camera showed that 43.9% had non-proliferative DR(NPDR) and 15.3% had PDR while the FOP camera showed that 40.2% had NPDR and 15.3% had PDR. The sensitivity and specificity for detecting any DR by FOP was 92.7% (95%CI 87.8–96.1) and 98.4% (95%CI 94.3–99.8) respectively and the kappa (ĸ) agreement was 0.90 (95%CI-0.85–0.95 p<0.001) while for STDR, the sensitivity was 87.9% (95%CI 83.2–92.9), specificity 94.9% (95%CI 89.7–98.2) and ĸ agreement was 0.80 (95%CI 0.71–0.89 p<0.001), compared to conventional photography. Conclusion Retinal photography using FOP camera is effective for screening and diagnosis of DR and STDR with high sensitivity and specificity and has substantial agreement with conventional retinal photography. PMID:26401839

  1. Rapid Grading of Fundus Photographs for Diabetic Retinopathy Using Crowdsourcing

    PubMed Central

    Villanti, Andrea C; Pearson, Jennifer L; Kirchner, Thomas R; Gupta, Omesh P; Shah, Chirag P

    2014-01-01

    Background Screening for diabetic retinopathy is both effective and cost-effective, but rates of screening compliance remain suboptimal. As screening improves, new methods to deal with screening data may help reduce the human resource needs. Crowdsourcing has been used in many contexts to harness distributed human intelligence for the completion of small tasks including image categorization. Objective Our goal was to develop and validate a novel method for fundus photograph grading. Methods An interface for fundus photo classification was developed for the Amazon Mechanical Turk crowdsourcing platform. We posted 19 expert-graded images for grading by Turkers, with 10 repetitions per photo for an initial proof-of-concept (Phase I). Turkers were paid US $0.10 per image. In Phase II, one prototypical image from each of the four grading categories received 500 unique Turker interpretations. Fifty draws of 1-50 Turkers were then used to estimate the variance in accuracy derived from randomly drawn samples of increasing crowd size to determine the minimum number of Turkers needed to produce valid results. In Phase III, the interface was modified to attempt to improve Turker grading. Results Across 230 grading instances in the normal versus abnormal arm of Phase I, 187 images (81.3%) were correctly classified by Turkers. Average time to grade each image was 25 seconds, including time to review training images. With the addition of grading categories, time to grade each image increased and percentage of images graded correctly decreased. In Phase II, area under the curve (AUC) of the receiver-operator characteristic (ROC) indicated that sensitivity and specificity were maximized after 7 graders for ratings of normal versus abnormal (AUC=0.98) but was significantly reduced (AUC=0.63) when Turkers were asked to specify the level of severity. With improvements to the interface in Phase III, correctly classified images by the mean Turker grade in four-category grading

  2. Automated microaneurysm detection in diabetic retinopathy using curvelet transform.

    PubMed

    Ali Shah, Syed Ayaz; Laude, Augustinus; Faye, Ibrahima; Tang, Tong Boon

    2016-10-01

    Microaneurysms (MAs) are known to be the early signs of diabetic retinopathy (DR). An automated MA detection system based on curvelet transform is proposed for color fundus image analysis. Candidates of MA were extracted in two parallel steps. In step one, blood vessels were removed from preprocessed green band image and preliminary MA candidates were selected by local thresholding technique. In step two, based on statistical features, the image background was estimated. The results from the two steps allowed us to identify preliminary MA candidates which were also present in the image foreground. A collection set of features was fed to a rule-based classifier to divide the candidates into MAs and non-MAs. The proposed system was tested with Retinopathy Online Challenge database. The automated system detected 162 MAs out of 336, thus achieved a sensitivity of 48.21% with 65 false positives per image. Counting MA is a means to measure the progression of DR. Hence, the proposed system may be deployed to monitor the progression of DR at early stage in population studies. PMID:26868326

  3. Folate status in type 2 diabetic patients with and without retinopathy

    PubMed Central

    Malaguarnera, Giulia; Gagliano, Caterina; Salomone, Salvatore; Giordano, Maria; Bucolo, Claudio; Pappalardo, Antonino; Drago, Filippo; Caraci, Filippo; Avitabile, Teresio; Motta, Massimo

    2015-01-01

    Background Folate deficiency is associated with cardiovascular disease, megaloblastic anemia, and with hyperhomocysteinemia. This study has been undertaken to investigate the role of folate status during the progression of the diabetic retinopathy. Methods We measured the plasma levels of homocysteine, folic acid, and red cell folate in 70 diabetic type 2 patients with nonproliferative diabetic retinopathy (NPDR), 65 with proliferative diabetic retinopathy (PDR), 96 without diabetic retinopathy, and 80 healthy subjects used as a control group. Results We found higher plasma levels of homocysteine in the NPDR group compared to the control group (P<0.001) and in the PDR group compared to control group (P<0.001) and NPDR group (P<0.01). The severity of diabetic retinopathy was associated with lower folic acid and red cell folate levels, and a significant difference was observed between PDR and NPDR groups (P<0.05). Conclusion The folate status could play a role in the development and progression of diabetic retinopathy. PMID:26300625

  4. Association Between IL-10 Gene Polymorphism and Diabetic Retinopathy

    PubMed Central

    Dong, Hongtao; Li, Qiuming; Wang, Menghua; Wan, Guangming

    2015-01-01

    Background Genetic and environmental factors both play important roles in the occurrence and progression of diabetic retinopathy (DR). IL-10 592 gene polymorphism is associated with diabetes pathogenesis. This study analyzed the relationship between IL-10 gene promoter-592 loci polymorphism (SNP) in a diabetic model rats with DR. Material/Methods Streptozotocin (STZ) was injected through the tail vein to establish a diabetic rat model. The rats were randomly divided into 2 groups for 3 months’ feeding, including 100 rats in the diabetes-positive control group and 100 rats only injected with citric acid buffer as the blank control group. Fundus fluorescein angiography (FFA) was used to observe retinal vascular changes. Polymerase chain reaction-restriction fragment polymorphisms assay (PCR-RFLP) was used to detect IL-10 gene promoter-592 loci polymorphism in DNA samples. Enzyme-linked immunosorbent assay (ELISA) was performed to test serum IL-10 concentration. Results Serum IL-10 level in DR rats was 33.18±5.0 pg/mL and in the control rats it was 53.33±4.16 pg/mL in (P<0.01). Diabetes susceptibility with IL-10-592 genotype frequency and gene frequency analysis showed that IL-10-592 genotype frequency and allele frequency were significantly different in the DR group compared with the control group (P<0.01). Conclusions IL-10 592 polymorphism was associated with DR susceptibility, suggesting that the gene polymorphism might be a risk factor for DR. PMID:26492380

  5. Beyond HbA1c: Environmental Risk Factors for Diabetic Retinopathy

    PubMed Central

    Nwanyanwu, Kristen Harris; Newman-Casey, Paula-Anne; Gardner, Thomas W; Lim, Jennifer I

    2015-01-01

    Diabetic retinopathy affects 4.2 million people in the United States and is the leading cause of blindness in working-aged people. As the prevalence of diabetes continues to rise, cost-effective interventions to decrease blindness from diabetic retinopathy will be paramount. While HbA1c and duration of disease are known risk factors, they account for only 11% of the risk of developing microvascular complications from the disease. The assessment of environmental risk factors for diabetic eye disease allows for the determination of modifiable population-level challenges that may be addressed to facilitate the end of blindness from diabetes. PMID:26973797

  6. Association of retinopathy and intima media thickness of common carotid artery in type 2 diabetic patients

    PubMed Central

    Momeni, Ali; Dyani, Mohamad Ali; Ebrahimi, Elnaz; Sedehi, Morteza; Naderi, Afsaneh

    2015-01-01

    Background: This study was carried out in order to evaluate the relationship between retinopathy and carotid intima-media thickness (CIMT). Materials and Methods: In a cross-sectional study, 154 diabetic patients who had a history of diabetic disease were evaluated in two equal groups of 77 patients with and without retinopathy, respectively. CIMT was evaluated in all of the patients. Results: Mean age of the patients was 59.65 ± 9.37 years. Mean CIMT of all patients was 0.84 ± 0.18. CIMT of patients with retinopathy was significantly greater than patients without retinopathy (P < 0.001). CIMT also correlated with age, duration of diabetes, systolic blood pressure, blood urea nitrogen, and serum creatinine. Conclusion: CIMT may be used as a simple, available and noninvasive method for screening of macro and microvascular complication of diabetic patients. PMID:26109997

  7. Impairment of Colour Vision in Diabetes with No Retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SNDREAMS- II, Report 3)

    PubMed Central

    Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Sharma, Tarun

    2015-01-01

    Purpose To assess impairment of colour vision in type 2 diabetics with no diabetic retinopathy and elucidate associated risk factors in a population-based cross-sectional study. Methods This is part of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular-genetics Study (SN-DREAMS II) which was conducted between 2007–2010. FM 100 hue-test was performed in 253 subjects with no clinical evidence of diabetic retinopathy. All subjects underwent detailed ophthalmic evaluation including cataract grading using LOCS III and 45° 4-field stereoscopic fundus photography. Various ocular and systemic risk factors for impairment of colour vision (ICV) were assessed in subjects with diabetes but no retinopathy. P value of < 0.05 was considered statistically significant. Results The mean age of the study sample was 57.08 ± 9.21 (range: 44–86 years). Gender adjusted prevalence of ICV among subjects with diabetes with no retinopathy was 39.5% (CI: 33.5–45.5). The mean total error score in the study sample was 197.77 ± 100 (range: 19–583). The risk factors for ICV in the study were women OR: 1.79 (1.00–3.18), increased resting heart rate OR: 1.04 (1.01–1.07) and increased intraocular pressure OR: 1.12 (1.00–1.24). Significant protective factor was serum high-density lipoprotein OR: 0.96 (0.93–0.99). Conclusions Acquired ICV is an early indicator of neurodegenerative changes in the retina. ICV found in diabetic subjects without retinopathy may be of non-vascular etiology. PMID:26053017

  8. Hybrid model for analysis of abnormalities in diabetic cardiomyopathy and diabetic retinopathy related images.

    PubMed

    Shaik, Fahimuddin; Sharma, Anil Kumar; Ahmed, Syed Musthak

    2016-01-01

    At present image processing methods hold a noteworthy position in unravelling various medical imaging challenges. The high risk disorders such as diabetic cardiomyopathy and diabetic retinopathy are considered as applications for proposed method. The dictum of this paper is on observing enhancement and segmentation of the cross sectional view of a blood capillary of a right coronary artery image of a diabetic patient and also retinal images. A hybrid model using hybrid morphological reconstruction technique as pre-processing with watershed segmentation method as post-processing is developed in this work. PMID:27186471

  9. Digital photographic screening for diabetic retinopathy in the James Bay Cree.

    PubMed

    Maberley, David; Cruess, Alan F; Barile, Gae; Slakter, Jason

    2002-07-01

    This study evaluates a single, 45-degree fundus image from a non-mydriatic camera for the triage of subjects at risk for diabetic retinopathy. A complete retinal assessment by a retina specialist was the main comparator for the camera. Inter-observer agreements were calculated for the reading of digital images with different grades of retinopathy. Two hundred eyes of 100 consecutive subjects were evaluated as part of the James Bay diabetic retinopathy screening project; 62% of subjects had no retinopathy, 12% had microaneurysms only, 24% had non-proliferative retinopathy, 5% had clinically significant macular edema (CSME), and 2% had proliferative disease (PDR). The Kappa statistic for two independent observers was 0.85 (p < 0.001) for the identification of retinopathy from the digital images. The sensitivity of the digital camera for the evaluation of any retinopathy was 84.4%, for CSME and/or PDR it was over 90%. The use of a single digital retinal image for the evaluation of diabetic retinopathy was performed with a high degree of inter-observer concordance and a high degree of sensitivity. PMID:12045884

  10. Levels of selected oxidative stress markers in the vitreous and serum of diabetic retinopathy patients

    PubMed Central

    Brzović-Šarić, Vlatka; Landeka, Irena; Šarić, Borna; Barberić, Monika; Andrijašević, Lidija; Cerovski, Branimir; Oršolić, Nada

    2015-01-01

    Purpose In diabetes, an impaired antioxidant defense system contributes to the development of diabetic retinopathy. The main objective of this paper was to find correlations of oxidative stress parameters within and between the vitreous and serum in patients with type 2 diabetes who had developed proliferative diabetic retinopathy. Methods The study included and compared two groups of patients who underwent vitrectomy: 37 patients with type 2 diabetes and proliferative retinopathy (PDR), and 50 patients with non-diabetic eye disorders (NDED). Vascular endothelial growth factor (VEGF), advanced oxidized protein product (AOPP), and oxidative stress markers (direct lipid hydroperoxidation (LPO), malondialdehyde (MDA), total superoxide dismutase (SOD), and glutathione (GSH)) were measured in the vitreous and serum of both groups and correlated with one another, between humoral compartments and with gender, age, and serum glucose levels. Results In the vitreous of PDR patients, VEGF, LPO, and MDA (p<0.05) were increased and SOD values were slightly lowered (p<0.05) than in NDED patients. Vitreous AOPP and GSH showed no differences between the groups. In the serum, AOPP, MDA, and SOD were increased (p<0.05) and VEGF was slightly increased (p<0.05) in the PDR group compared to NDED. With regard to gender, similar changes were recorded for both groups, except for the lower serum MDA in males than females in the NDED group. Advanced age showed no significant effect on changes of measured parameters in the vitreous. In the serum, VEGF was positively correlated (p<0.05) and MDA and SOD negatively correlated (p<0.05) with increasing age. Among measured parameters within and between the vitreous and serum, several correlative links occurred in the PDR group that were not present in the NDED group. The most prominent correlation changes were between serum LPO and vitreal LPO, serum SOD and vitreal LPO, serum LPO and serum SOD, and vitreal VEGF and serum SOD. Conclusions Among

  11. High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera

    PubMed Central

    Soliman, Mohamed Kamel; Hassan, Muhammad; Hanout, Mostafa; Graf, Frank; High, Robin; Do, Diana V.; Nguyen, Quan Dong; Sepah, Yasir J.

    2016-01-01

    Purpose To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus. Methods An adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors. Results Ten healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes. Conclusions The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its

  12. Genetics in diabetic retinopathy: current concepts and new insights.

    PubMed

    Simó-Servat, Olga; Hernández, Cristina; Simó, Rafael

    2013-08-01

    There is emerging evidence which indicates the essential role of genetic factors in the development of diabetic retinopathy (DR). In this regard it should be highlighted that genetic factors account for 25-50% of the risk of developing DR. Therefore, the use of genetic analysis to identify those diabetic patients most prone to developing DR might be useful in designing a more individualized treatment. In this regard, there are three main research strategies: candidate gene studies, linkage studies and Genome-Wide Association Studies (GWAS). In the candidate gene approach, several genes encoding proteins closely related to DR development have been analyzed. The linkage studies analyze shared alleles among family members with DR under the assumption that these predispose to a more aggressive development of DR. Finally, Genome-Wide Association Studies (GWAS) are a new tool involving a massive evaluation of single nucleotide polymorphisms (SNP) in large samples. In this review the available information using these three methodologies is critically analyzed. A genetic approach in order to identify new candidates in the pathogenesis of DR would permit us to design more targeted therapeutic strategies in order to decrease this devastating complication of diabetes. Basic researchers, ophthalmologists, diabetologists and geneticists should work together in order to gain new insights into this issue. PMID:24403848

  13. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1) Signaling Pathway in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Sohn, Eunjin; Kim, Junghyun; Kim, Chan-Sik; Lee, Yun Mi; Kim, Jin Sook

    2016-03-01

    High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes. PMID:26950148

  14. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1) Signaling Pathway in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sohn, Eunjin; Kim, Junghyun; Kim, Chan-Sik; Lee, Yun Mi; Kim, Jin Sook

    2016-01-01

    High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes. PMID:26950148

  15. Study of Pigment Epithelium-derived Factor in Pathogenesis of Diabetic Retinopathy.

    PubMed

    Zang, Jing; Guan, Guoqi

    2015-06-01

    Diabetic retinopathy (DR), a major microvascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among adults worldwide. However, aside from pathological damage, the traditional laser and multi-needle operation treatments required for more advanced disease can cause further damage to the visual field and increase the operation risk. Therefore, the development of new therapeutic strategies for the prevention and treatment of DR is essential. Some emerging evidence now indicates that pigment epithelium-derived factor (PEDF), a multifunctional protein, can target multiple pathways to exert neurotropic, neuropro- tective, anti-angiogenic, anti-vasopermeability, anti-inflammation, anti-thrombogenic, and anti-oxidative effects against DR. This review addresses the functions of PEDF in different pathways that could lead to potential therapeutics for the treatment of DR. PMID:26902068

  16. [A familial case of proliferative diabetic retinopathy associated with a mutation in the mitochondrial gene].

    PubMed

    Kuze, M; Arima, M; Saso, M; Uji, Y

    1998-11-01

    We report a 39-year-old male patient with proliferative diabetic retinopathy associated with a mutation in the mitochondrial DNA and with his family. The patient was referred for fundus examination in 1993. He had been diagnosed as having diabetes mellitus 15 years before but his diabetic control was not good. He was thin and short and presented with bilateral proliferative diabetic retinopathy. When he received pan retinal photocoagulation, an exudative retinal detachment was found in his left eye, but it disappeared spontaneously. The patient's history included sensorineural deafness and autonomic nerve system disorder. Mitochondrial analysis obtained from blood showed mutation of adenine to guanine at mitochondrial DNA 3243. Generally speaking, mitochondrial disorders often include pigmentary degeneration. For this reason diabetic patients with mitochondrial disorders rarely suffer proliferative diabetic retinopathy. In this case, the retinitis pigmentosa was not so severe as to cause the proliferative change, so that it was probably derived from heteroplasmy. PMID:9852718

  17. Influence of retinopathy on the achromatic and chromatic vision of patients with type 2 diabetes

    PubMed Central

    2014-01-01

    Background Luminance contrast sensitivity and colour vision are considered to have great predictive value in the evaluation of type 2 diabetic retinopathy. However, these two visual characteristics have seldom been investigated in the same group of patients. In the present study we measured contrast sensitivity and colour vision in a group of patients with type 2 diabetes and correlated the results with estimates of common metabolic markers for the disease. A subgroup of the patients had no clinical signs of retinopathy. Methods The vision of 27 patients (n = 50 eyes) with type 2 diabetes, with retinopathy (n = 20 eyes), or without retinopathy (n = 30 eyes) were evaluated using two psychophysical tests, the Farnsworth–Munsell 100 hue test (FM 100), and measurements of the luminance contrast sensitivity at 11 spatial frequencies. The results were compared with measurements obtained from an age-matched control group (n = 32), and were correlated with the level of glycated haemoglobin, glycaemic level, and time of disease onset. Signs of retinopathy were identified during the ophthalmological examinations. Results Contrast sensitivity and colour vision impairments were present at different levels in diabetes patients. Eyes with retinopathy showed more severe vision loss than eyes without retinopathy. The FM 100 test was more sensitive for separation of patients from controls. Colour vision loss had no colour axes preference. The contrast sensitivity test appeared to have some advantage in differentiating patients with retinopathy from patients without retinopathy. Conclusions Both methods can be useful to follow the visual function of diabetic patients and should be used together to discriminate patients from controls, as well as to identify early signs of retinal damage. PMID:25174264

  18. Glycation and Carboxymethyllysine Levels in Skin Collagen Predict the Risk of Future 10-Year Progression of Diabetic Retinopathy and Nephropathy in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications Participants With Type 1 Diabetes

    PubMed Central

    Genuth, Saul; Sun, Wanjie; Cleary, Patricia; Sell, David R.; Dahms, William; Malone, John; Sivitz, William; Monnier, Vincent M.

    2009-01-01

    Several mechanistic pathways linking hyperglycemia to diabetes complications, including glycation of proteins and formation of advanced glycation end products (AGEs), have been proposed. We investigated the hypothesis that skin collagen glycation and AGEs predict the risk of progression of microvascular disease. We measured glycation products in the skin collagen of 211 Diabetes Control and Complications Trial (DCCT) volunteers in 1992 who continued to be followed in the Epidemiology of Diabetes Interventions and Complications study for 10 years. We determined whether the earlier measurements of glycated collagen and AGE levels correlated with the risk of progression of retinopathy and nephropathy from the end of the DCCT to 10 years later. In multivariate analyses, the combination of furosine (glycated collagen) and carboxymethyllysine (CML) predicted the progression of retinopathy (χ2 = 59.4, P < 0.0001) and nephropathy (χ2 = 18.2, P = 0.0001), even after adjustment for mean HbA1c (A1C) (χ2 = 32.7, P < 0.0001 for retinopathy) and (χ2 = 12.8, P = 0.0016 for nephropathy). The predictive effect of A1C vanished after adjustment for furosine and CML (χ2 = 0.0002, P = 0.987 for retinopathy and χ2 = 0.0002, P = 0.964 for nephropathy). Furosine explained more of the variation in the 10-year progression of retinopathy and nephropathy than did CML. These results strengthen the role of glycation of proteins and AGE formation in the pathogenesis of retinopathy and nephropathy. Glycation and subsequent AGE formation may explain the risk of these complications associated with prior A1C and provide a rational basis for the phenomenon of “metabolic memory” in the pathogenesis of these diabetes complications. PMID:16249432

  19. pEPito-driven PEDF Expression Ameliorates Diabetic Retinopathy Hallmarks.

    PubMed

    Calado, Sofia M; Diaz-Corrales, Francisco; Silva, Gabriela A

    2016-04-01

    Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus. It is characterized by retinal microvascular changes caused by chronic exposure to hyperglycemia, leading to low tissue oxygenation and ultimately to neovascularization. Laser photocoagulation and vitrectomy are the most efficient treatments for DR, but display severe side effects such as the destruction of the healthy retina. Another clinical approach uses antiangiogenic agents to prevent and delay progression of neovascularization, but these require recurrent local administrations that increase the possibility of retinal detachment, vitreous hemorrhage, and cataract formation. Studies in human diabetic retinas have revealed an imbalance between proangiogenic factors such as the vascular endothelial growth factor (VEGF) and antiangiogenic factors, such as pigment epithelial-derived factor (PEDF). This imbalance favors pathological angiogenesis contributing to DR, and can constitute a therapeutic target. Gene therapy was recently shown to be an adequate intervention for long-term treatment of several retinal pathologies. We have previously shown the newly engineered episomal vector pEPito to be able of sustained gene expression in the mouse retina. We here show that pEPito was able to overexpress PEDF for up to three months, both in in vitro cultures of human retinal pigment epithelial cells and in the retina of diabetic mice after a single subretinal injection. In vivo, in parallel with the increase in PEDF we observed a decrease in VEGF levels in injected compared with noninjected eyes and a significant effect on two hallmarks of DR: reduction of glucose transport (by glucose transporter GLUT1), and reduction of inflammation by decreased reactivity of microglia. Jointly, these results point to a significant therapeutic potential of gene therapy with pEPito-PEDF for the treatment of DR. PMID:26942449

  20. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment

    PubMed Central

    Abcouwer, Steven F.; Gardner, Thomas W.

    2014-01-01

    Diabetic retinopathy (DR) impairs vision of patients with type 1 and type 2 diabetes, associated with vascular dysfunction and occlusion, retinal edema, hemorrhage, and inappropriate growth of new blood vessels. The recent success of biologic treatments targeting vascular endothelial growth factor (VEGF) demonstrates that treating the vascular aspects in the later stages of the disease can preserve vision in many patients. It would also be highly desirable to prevent the onset of the disease or arrest its progression at a stage preceding the appearance of overt microvascular pathologies. The progression of DR is not necessarily linear but may follow a series of steps that evolve over the course of multiple years. Abundant data suggest that diabetes affects the entire neurovascular unit of the retina, with an early loss of neurovascular coupling, gradual neurodegeneration, gliosis, and neuroinflammation before observable vascular pathologies. In this article, we consider the pathology of diabetic retinopathy from the point of view that diabetes causes measurable dysfunctions in the complex integral network of cell types that produce and maintain human vision. PMID:24673341

  1. Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

    PubMed Central

    Salinero-Fort, Miguel Á.; San Andrés-Rebollo, Francisco Javier; de Burgos-Lunar, Carmen; Arrieta-Blanco, Francisco Jesús; Gómez-Campelo, Paloma

    2013-01-01

    Objective To evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study. Design The MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain). Results The cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04–9.22) and the incidence density was 2.03 (95% CI = 1.75–2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10–2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39–18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18–3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30–2.77), and aspirin use (HR = 1.65; 95% CI = 1.22–2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75–1.82) and being female (HR = 1.12; 95% CI = 0.84–1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use. Conclusions After a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of

  2. Natural history of retinopathy in children and young people with type 1 diabetes.

    PubMed

    Dhillon, N; Karthikeyan, A; Castle, A; Dodson, P; Högler, W; Kirk, J; Krone, N; Nolan, J; Barrett, T

    2016-07-01

    PurposeTo describe the prevalence and natural history of retinopathy in a cohort of children and young people with type 1 diabetes attending a tertiary hospital diabetes clinic.MethodsWe analysed retinopathy screening data from 2008 to 2010 on all eligible children using the 'Twinkle' diabetes database and the regional retinal screening database.ResultsA total of 88% (149/169) of eligible children were screened in 2008, median age 14 years, 52% male. The prevalence of retinopathy was 19.5% (30/149). All children had background retinopathy grade R1. There was significant difference in median (range) duration of diabetes, 7.7 years (0.6-13.7) vs 5 years (0.2-12.5) (P<0.001) and median (range) HbA1C, 9.1% (7.2-14) vs 8.6% (5.6-13.1) (P=0.02), between the groups with and without retinopathy. At 2- years follow-up, 12/30 (40%) had unchanged retinopathy grade R1, 10/30 (33.3%) showed resolution of changes (R0), 1/30 progressed to maculopathy, and 7/30 had no follow-up data. Median (range) HbA1C in 2008 and 2010 for the groups with stable vs resolved changes was similar, 9.1% (7.2-14.0) and 9.2% (7-14.0) vs 9.5% (7.8-14.0) and 9.2% (8.7-14.0). Of the 119 without retinopathy in 2008, 27 (22.5%) had developed retinopathy within 2 years, including 1 with pre-proliferative retinopathy and 1 with maculopathy. There was no significant difference in HbA1c between those who progressed to retinopathy (8.7% (7.1-13.1)) (8.7% (7.1-13.1)), and those who did not (8.6% (6.3-12.2)).ConclusionsPrevalence of background retinopathy in our cohort was comparable to the previously published reports, with higher HbA1c and longer duration of diabetes being significant risk factors. On short-term follow-up, Grade 1 retinopathy is likely to resolve in a third of patients and remain unchanged in just over a third. PMID:27101752

  3. Risk factors for diabetic retinopathy in northern Chinese patients with type 2 diabetes mellitus

    PubMed Central

    Yan, Zhi-Peng; Ma, Jing-Xue

    2016-01-01

    AIM To investigate the prevalence and risk factors of diabetic retinopathy (DR) in northern Chinese patients with type 2 diabetes mellitus (T2DM). METHODS This retrospective cross-sectional study was performed between May 2011 and April 2012. A total of 1100 patients (male/female, 483/617) were included in this study. DR was defined following the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. All included patients accepted a comprehensive ophthalmic examination including retinal photographs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for age and gender. RESULTS Retinopathy was present in 307 patients with a prevalence of 27.9%. In univariate logistic analysis, presence of DR was associated with longer duration of diabetes (OR, 5.70; 95%CI, 2.91-12.56), higher concentration of fasting blood glucose (OR, 12.94; 95%CI, 2.40-67.71), higher level of glycosylated hemoglobin HbA1c (OR, 5.50; 95%CI, 3.78-11.97) and insulin treatment (OR, 6.99; 95%CI, 1.39-35.12). The lifestyle of patients with T2DM including smoking, alcohol consumption and regular exercise seemed not associated with the development of DR. CONCLUSION Our study suggests that fasting serum glucose concentration, HbA1c level, duration of diabetes and insulin treatment are potential risk factors for DR in northern Chinese patients with T2DM, while the lifestyle of included patients seems not associated with DR. PMID:27588275

  4. Univariate and multivariate analysis of associated factors of retinopathy in 894 Italian adult diabetics.

    PubMed

    Pisu, E; Vitelli, F; Coggi, G; Franzone, M; Cavallo, M; Chiara, E; Carta, Q; Pagano, G

    1988-12-01

    The prevalence of diabetic retinopathy and the evaluation of its risk factors is poorly known in Italian population. Therefore, we have studied 894 diabetic outpatients (420 males, 474 females, 27.6% IDDs, 38.1% insulin-treated) in order to investigate the effect of clinical and metabolic characteristics on the frequency of diabetic retinopathy, classified into six different classes. In univariate analyses age, duration of disease, systolic and diastolic blood pressure, blood urea nitrogen, 24 hr proteinuria and fasting glycemia significantly correlated (p less than 0.001) with severity of retinopathy. The significance was confirmed in multivariate analysis for duration, age and systolic blood pressure (p less than 0.001). Stratification by type of diabetes showed that undefined onset of diabetes probably reduced in NID patients the power of duration as an associated factor of retinopathy. Worsening of this complication in three clinical classes of therapy (diet, oral and insulin-treatment) is evident too. Finally, our 11 variables in the step-wise multiple-regression analysis explain only 16.8% of diabetic retinopathy in all patients, but 36.6% in selected ID subjects. PMID:3246287

  5. Detection of Neovascularization Based on Fractal and Texture Analysis with Interaction Effects in Diabetic Retinopathy

    PubMed Central

    Lee, Jack; Zee, Benny Chung Ying; Li, Qing

    2013-01-01

    Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA), high order spectrum analysis (HOS), fractal analysis (FA), and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1% and 98.5% (99.3%), respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients. PMID:24358105

  6. Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy.

    PubMed

    Bolinger, Mark T; Antonetti, David A

    2016-01-01

    Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin-kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies. PMID:27618014

  7. Automatic detection of diabetic retinopathy exudates from non-dilated retinal images using mathematical morphology methods.

    PubMed

    Sopharak, Akara; Uyyanonvara, Bunyarit; Barman, Sarah; Williamson, Thomas H

    2008-12-01

    Diabetic retinopathy is a complication of diabetes that is caused by changes in the blood vessels of the retina. The symptoms can blur or distort the patient's vision and are a main cause of blindness. Exudates are one of the primary signs of diabetic retinopathy. Detection of exudates by ophthalmologists normally requires pupil dilation using a chemical solution which takes time and affects patients. This paper investigates and proposes a set of optimally adjusted morphological operators to be used for exudate detection on diabetic retinopathy patients' non-dilated pupil and low-contrast images. These automatically detected exudates are validated by comparing with expert ophthalmologists' hand-drawn ground-truths. The results are successful and the sensitivity and specificity for our exudate detection is 80% and 99.5%, respectively. PMID:18930631

  8. Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We performed a cross-sectional, observational study of 351 U.S. residents with at least 50 years of insulin-dependent diabetes. Longitudinal data on retinopathy progression was obtained via chart review in patients followed at the Joslin Diabetes Center eye clinic (Boston, MA). HbA1c was determined ...

  9. Potential Role of Endoplasmic Reticulum Stress in Pathogenesis of Diabetic Retinopathy.

    PubMed

    Sánchez-Chávez, Gustavo; Hernández-Ramírez, Ernesto; Osorio-Paz, Ixchel; Hernández-Espinosa, Claudia; Salceda, Rocío

    2016-05-01

    Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Multiple biochemical abnormalities have been proposed to explain the development of retinopathy, including oxidative stress. Although the existence of oxidative stress has been established in the retina from long standing diabetic animals, pathogenesis and progression of retinopathy remain unclear. In order to gain insight into the pathogenesis of diabetic retinopathy, we analyzed the levels of different oxidative stress biomarkers in the retina at early stages during the progress of streptozotocin-induced diabetes. No significant changes in glutathione content, expression of NADPH-oxidase, levels of lipid peroxidation, nor production of free radicals were observed in the retina up to 45 days of diabetes induction. Likewise, a transient decrease in aconitase activity, parallel to an increase in the superoxide dismutase activity was observed at 20 days of hyperglycemia, suggesting a high capacity of retina to maintain its redox homeostasis, at least at early stages of diabetes. Nonetheless, we found an early and time-dependent increase in the levels of oxidized proteins, which was not affected by the administration of the antioxidant quercetin. Also, positive immunoreactivity to the reticulum stress protein CHOP was found in glial Müller cells of diabetic rat retinas. These findings suggest the occurrence of endoplasmic reticulum stress as a primary event in retina pathogenesis in diabetes. PMID:26721508

  10. Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

    PubMed Central

    Rodríguez-Poncelas, Antonio; Mundet-Tudurí, Xavier; Miravet-Jiménez, Sonia; Casellas, Aina; Barrot-De la Puente, Joan F.; Franch-Nadal, Josep; Coll-de Tuero, Gabriel

    2016-01-01

    Purpose To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain). Methods This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m2 and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy. Results CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m2 [OR], 95% confidence interval [CI], 1.3 (1.1–1.6). Conclusions These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population. PMID:26886129

  11. Computer-aided diabetic retinopathy detection using trace transforms on digital fundus images.

    PubMed

    Ganesan, Karthikeyan; Martis, Roshan Joy; Acharya, U Rajendra; Chua, Chua Kuang; Min, Lim Choo; Ng, E Y K; Laude, Augustinus

    2014-08-01

    Diabetic retinopathy (DR) is a leading cause of vision loss among diabetic patients in developed countries. Early detection of occurrence of DR can greatly help in effective treatment. Unfortunately, symptoms of DR do not show up till an advanced stage. To counter this, regular screening for DR is essential in diabetic patients. Due to lack of enough skilled medical professionals, this task can become tedious as the number of images to be screened becomes high with regular screening of diabetic patients. An automated DR screening system can help in early diagnosis without the need for a large number of medical professionals. To improve detection, several pattern recognition techniques are being developed. In our study, we used trace transforms to model a human visual system which would replicate the way a human observer views an image. To classify features extracted using this technique, we used support vector machine (SVM) with quadratic, polynomial, radial basis function kernels and probabilistic neural network (PNN). Genetic algorithm (GA) was used to fine tune classification parameters. We obtained an accuracy of 99.41 and 99.12% with PNN-GA and SVM quadratic kernels, respectively. PMID:24958614

  12. Scientometric Analysis and Mapping of Scientific Articles on Diabetic Retinopathy

    PubMed Central

    RAMIN, Shahrokh; GHAREBAGHI, Reza; HEIDARY, Fatemeh

    2015-01-01

    Diabetic retinopathy (DR) is the major cause of blindness among the working-age population globally. No systematic research has been previously performed to analyze the research published on DR, despite the need for it. This study aimed to analyze the scientific production on DR to draw overall roadmap of future research strategic planning in this field. A bibliometric method was used to obtain a view on the scientific production about DR by the data extracted from the Institute for Scientific Information (ISI). Articles about DR published in 1993–2013 were analyzed to obtain a view of the topic’s structure, history, and to document relationships. The trends in the most influential publications and authors were analyzed. Most highly cited articles addressed epidemiologic and translational research topics in this field. During the past 3 years, there has been a trend toward biomarker discovery and more molecular translational research. Areas such as gene therapy and micro-RNAs are also among the recent hot topics. Through analyzing the characteristics of papers and the trends in scientific production, we performed the first scientometric report on DR. Most influential articles have addressed epidemiology and translational research subjects in this field, which reflects that globally, the earlier diagnosis and treatment of this devastating disease still has the highest global priority. PMID:27350949

  13. Automated detection of diabetic retinopathy in retinal images

    PubMed Central

    Valverde, Carmen; García, María; Hornero, Roberto; López-Gálvez, María I

    2016-01-01

    Diabetic retinopathy (DR) is a disease with an increasing prevalence and the main cause of blindness among working-age population. The risk of severe vision loss can be significantly reduced by timely diagnosis and treatment. Systematic screening for DR has been identified as a cost-effective way to save health services resources. Automatic retinal image analysis is emerging as an important screening tool for early DR detection, which can reduce the workload associated to manual grading as well as save diagnosis costs and time. Many research efforts in the last years have been devoted to developing automatic tools to help in the detection and evaluation of DR lesions. However, there is a large variability in the databases and evaluation criteria used in the literature, which hampers a direct comparison of the different studies. This work is aimed at summarizing the results of the available algorithms for the detection and classification of DR pathology. A detailed literature search was conducted using PubMed. Selected relevant studies in the last 10 years were scrutinized and included in the review. Furthermore, we will try to give an overview of the available commercial software for automatic retinal image analysis. PMID:26953020

  14. Scientometric Analysis and Mapping of Scientific Articles on Diabetic Retinopathy.

    PubMed

    Ramin, Shahrokh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Diabetic retinopathy (DR) is the major cause of blindness among the working-age population globally. No systematic research has been previously performed to analyze the research published on DR, despite the need for it. This study aimed to analyze the scientific production on DR to draw overall roadmap of future research strategic planning in this field. A bibliometric method was used to obtain a view on the scientific production about DR by the data extracted from the Institute for Scientific Information (ISI). Articles about DR published in 1993-2013 were analyzed to obtain a view of the topic's structure, history, and to document relationships. The trends in the most influential publications and authors were analyzed. Most highly cited articles addressed epidemiologic and translational research topics in this field. During the past 3 years, there has been a trend toward biomarker discovery and more molecular translational research. Areas such as gene therapy and micro-RNAs are also among the recent hot topics. Through analyzing the characteristics of papers and the trends in scientific production, we performed the first scientometric report on DR. Most influential articles have addressed epidemiology and translational research subjects in this field, which reflects that globally, the earlier diagnosis and treatment of this devastating disease still has the highest global priority. PMID:27350949

  15. Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

    PubMed Central

    Hernández, Cristina; Simó, Rafael

    2016-01-01

    Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed. PMID:27123463

  16. Serum Magnesium Concentration Is Inversely Associated with Albuminuria and Retinopathy among Patients with Diabetes

    PubMed Central

    Lu, Jun; Gu, Yuying; Guo, Meixiang; Chen, Peihong; Wang, Hongtao

    2016-01-01

    Aim. To investigate the association between serum magnesium levels and microvascular complications among patients with diabetes. Methods. Patients with diabetes were recruited between April 2012 and January 2015. All patients received an assay of serum magnesium concentration, were screened for 24 h albumin excretion rate, and underwent nonmydriatic fundus photography. Albuminuria and retinopathy were defined accordingly. A total of 3,100 patients with normal serum magnesium levels were included in this study. Results. Patients with albuminuria and/or retinopathy had lower levels of serum magnesium than patients without these complications (P < 0.001). The prevalence of isolated albuminuria, isolated retinopathy, and combined albuminuria and retinopathy decreased as the concentration of serum magnesium increased. Multiple logistic regression analysis indicated that the odds ratio for isolated albuminuria, isolated retinopathy, and concomitant albuminuria and retinopathy decreased by approximately 20% for every 0.1 mmol/L increase in serum magnesium concentration. Conclusion. Serum magnesium levels were negatively associated with the risk of diabetic microvascular complications among patients with serum magnesium levels within the normal range. PMID:27547762

  17. Th1/Th2 cytokine expression in diabetic retinopathy.

    PubMed

    Cao, Y L; Zhang, F Q; Hao, F Q

    2016-01-01

    Diabetic retinopathy (DR), an important complication of diabetes mellitus (DM), is not well understood. T helper cell balance (Th1/Th2) is involved in various autoimmune diseases; however, its role in DR is not understood. This study explores changes in Th1 and Th2 cytokine expression during DR. Blood samples were collected from 25 healthy volunteers (normal control group), 35 patients with type 2 DM (T2DM group) without DR, and 30 cases of T2DM patients with DR (DR group). Real-time PCR was used to measure mRNA expression of IL-2 and TNF-α, secreted from Th1 cells, and of IL-4 and IL-10, secreted from Th2 cells. We used ELISA to detect cytokine expression in serum to analyze the correlation between Th1 and Th2 cytokines. IL-2 and TNF-αmRNA and protein expression levels in the T2DM and DR groups were significantly higher than in the normal control group (P < 0.05). Compared with the T2DM group, the DR group had higher IL-2 and TNF-αlevels (P < 0.05). IL-4 and IL-10 levels were lower in the DR group compared with the normal and T2DM groups (P < 0.05), while T2DM showed no difference compared with the normal control (P > 0.05). IL-2 and TNF-αwere negatively correlated with IL-4 and IL-10 in the DR group, respectively. We found that Th1 cytokine secretion was higher and Th2 cytokines secretion was lower during DR, leading to a Th1/ Th2 imbalance, suggesting that Th1/Th2 imbalance is a side effect for DR occurrence and development. PMID:27525838

  18. Diabetic care initiatives to prevent blindness from diabetic retinopathy in India

    PubMed Central

    Murthy, GVS; Das, Taraprasad

    2016-01-01

    It is estimated that 65 million (17%) of 382 million persons with diabetes mellitus (DM) globally reside in India. While globally 35% persons with DM have diabetic retinopathy (DR), this proportion is reportedly lower in India, other countries in South Asia and China. We reviewed published data from 2008 onwards from PubMed, which ascertained DR in population-based representative samples. We also reviewed the risk factors for DR, on awareness regarding eye complications and on accessing an eye examination. Thirteen research studies have reported on the prevalence of DR among persons with DM; this prevalence was lower than the global level in China, India, and Nepal. Eleven studies reported DR risk factors association. The duration of diabetes and level of glycemic control were universally acknowledged DR risk factors. We identified 7 studies in the Asia region that researched the level of awareness about diabetes eye complications and the practice of accessing an eye examination. Excepting 1 study in China, others reported a significant proportion being aware that diabetes leads to eye complications. But the awareness was not translated into a positive practice-most studies reported only 20–50% of the persons with diabetes actually having had their eyes examined. The present review highlights the observation that the risk factors for DR need an integrated diabetic care pathway where the eye care team has to work in close collaboration and partnership with a diabetic care team has to reduce the risk of blindness from DR. PMID:26953024

  19. An integrated index for the identification of diabetic retinopathy stages using texture parameters.

    PubMed

    Acharya, U Rajendra; Ng, E Y K; Tan, Jen-Hong; Sree, S Vinitha; Ng, Kwan-Hoong

    2012-06-01

    Diabetes is a condition of increase in the blood sugar level higher than the normal range. Prolonged diabetes damages the small blood vessels in the retina resulting in diabetic retinopathy (DR). DR progresses with time without any noticeable symptoms until the damage has occurred. Hence, it is very beneficial to have the regular cost effective eye screening for the diabetes subjects. This paper documents a system that can be used for automatic mass screenings of diabetic retinopathy. Four classes are identified: normal retina, non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and macular edema (ME). We used 238 retinal fundus images in our analysis. Five different texture features such as homogeneity, correlation, short run emphasis, long run emphasis, and run percentage were extracted from the digital fundus images. These features were fed into a support vector machine classifier (SVM) for automatic classification. SVM classifier of different kernel functions (linear, radial basis function, polynomial of order 1, 2, and 3) was studied. Receiver operation characteristics (ROC) curves were plotted to select the best classifier. Our proposed system is able to identify the unknown class with an accuracy of 85.2%, and sensitivity, specificity, and area under curve (AUC) of 98.9%, 89.5%, and 0.972 respectively using SVM classifier with polynomial kernel of order 3. We have also proposed a new integrated DR index (IDRI) using different features, which is able to identify the different classes with 100% accuracy. PMID:21340703

  20. Nonmydriatic Fundus Photography for Teleophthalmology Diabetic Retinopathy Screening in Rural and Urban Clinics

    PubMed Central

    Chin, Eric K.; Ventura, Bruna V.; See, Kai-Yin; Seibles, Joann

    2014-01-01

    Abstract Purpose: To evaluate the relative diagnostic value of nonmydriatic fundus photography (nFP) among patients screened for diabetic retinopathy in remote rural medical clinics and an urban academic medical center for nonadherence to recommended annual dilated eye examination. Subjects and Methods: A retrospective cross-sectional study was performed among diabetic patients seen in primary outpatient clinics between 2006 and 2011 who were screened for diabetic retinopathy with nFP for history of nonadherence to recommended annual dilated eye examination. A single nonstereoscopic, 45°, 10-megapixel digital image of the disc and macula of both eyes was obtained locally and transmitted electronically to a retinal specialist for remote review. The results from remote rural Native American Indian reservations were compared with those from an urban academic family practice clinic. The proportion of subjects diagnosed with diabetic retinopathy and the quality of fundus images were compared. Results: Among 872 patients (1,744 eyes) screened from rural sites and 517 subjects (1,034 eyes) screened from an urban site, images were of good quality for evaluation in 82.4% and 85.7% of subjects, respectively. Diabetic retinopathy was noted in 12.6% of rural subjects and 29.6% of urban subjects (p<0.001). Conclusions: nFP can be a useful tool in both rural and urban settings to screen for diabetic retinopathy in patients who are nonadherent to the recommended dilated annual eye exam. In our study population, a surprisingly higher percentage of diabetic subjects screened from the urban clinic had retinopathy compared with subjects screened in rural clinics. PMID:24219153

  1. The 5-Year Onset and Regression of Diabetic Retinopathy in Chinese Type 2 Diabetes Patients

    PubMed Central

    Jin, Peiyao; Peng, Jinjuan; Zou, Haidong; Wang, Weiwei; Fu, Jiong; Shen, Binjie; Bai, Xuelin; Xu, Xun; Zhang, Xi

    2014-01-01

    Purpose To determine the rate and risk factors of diabetic retinopathy (DR) onset and regression in Chinese type 2 diabetes mellitus patients. Methods This is a 5-year community-based prospective study. The demographic information, systemic examination results and ophthalmological test results of each participant were collected. The study outcomes were DR incidence, defined as the onset of DR in at least one eye, and DR regression, defined as full regression from existing DR to no retinopathy without invasive treatments. The associations between each potential risk factor and the outcomes were studied. Results In total, 778 participants were enrolled. There were 322 patients without DR at baseline, of which 151 participants developed DR during follow-up (DR incidence rate = 46.89%). Baseline hyperglycemia and high blood pressure were two independent risk factors associated with DR incidence. Among the 456 participants with existing DR at entry, 110 fully recovered after 5 years (DR regression rate = 24.12%). Low baseline glucose and low serum triglyceride were two independent factors associated with DR regression. Conclusions DR incidence occurred more frequently in patients with hyperglycemia and high blood pressure. DR regression occurred mostly in patients with lower glucose and lower serum triglyceride levels among Chinese type 2 diabetes patients. PMID:25402474

  2. Effects of arctiin on streptozotocin-induced diabetic retinopathy in Sprague-Dawley rats.

    PubMed

    Lu, Lai-chun; Zhou, Wei; Li, Zhuo-heng; Yu, Cai-ping; Li, Chen-wen; Luo, Ming-he; Xie, Hong

    2012-08-01

    Diabetic retinopathy is one of the most common and severe complications of diabetes mellitus. Arctiin, a bioactive compound isolated from the dry seeds of Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on the serum glucose and HBA1c levels, the blood viscosity, and VEGF expression in the retinal tissues of rats with diabetic retinopathy. We first extracted arctiin from Fructus Arctii and then investigated its chemopreventive effect on streptozotocin-induced diabetic retinopathy in male Sprague-Dawley rats. After the induction of diabetes using streptozotocin (30 mg/kg, i. p.), the rats were randomly divided into five groups (n = 20 per group) and treated with intragastric doses of 30, 90, or 270 mg/kg/d wt of arctiin, 100 mg/kg/d wt of calcium dobesilate, or 0.5 % CMC-Na. Twenty nondiabetic sham-treated rats were treated with 0.5 % CMC-Na. The occurrence of diabetic retinopathy did not differ dramatically among the groups. However, at week 16, the glycosylated haemoglobin (HBA1c) level was significantly decreased in all of the arctiin-treated groups when compared with the control group, and the serum glucose level was also decreased in the rats treated with the highest dose of arctiin. In addition, treatment with arctiin ameliorated retinal oedema, detachment of the retina, and VEGF expression in the retina, as detected using histological and immunochemical examinations. Finally, arctiin increased the viability of retinal microvascular endothelial cells in vitro. Together, these findings demonstrate that arctiin decreases the severity of diabetic complications, demonstrating the importance of this compound as an inhibitor of diabetic retinopathy. PMID:22753037

  3. Detection of retinal lesions in diabetic retinopathy: comparative evaluation of 7-field digital color photography versus red-free photography.

    PubMed

    Venkatesh, Pradeep; Sharma, Reetika; Vashist, Nagender; Vohra, Rajpal; Garg, Satpal

    2015-10-01

    (average κ = 0.51, range 0.45-0.54). Fair agreement was noted for detection of microaneurysms (average κ = 0.29, range 0.20-0.39) and IRMA (average κ = 0.23, range 0.23-0.24). Inter-observer agreement with color images was substantial for hemorrhages (average κ = 0.72), soft exudates (average κ = 0.65), and NVD (average κ = 0.65); moderate for microaneurysms (average κ = 0.42), NVE (average κ = 0.44), and hard exudates (average κ = 0.59) and fair for IRMA (average κ = 0.21). Inter-observer agreement with red-free images was substantial for hard exudates (average κ = 0.63) and moderate for detection of hemorrhages (average κ = 0.56), SE (average κ = 0.60), IRMA (average κ = 0.50), NVE (average κ = 0.44), and NVD (average κ = 0.45). Digital red-free photography has a higher level of detection ability for all retinal lesions of diabetic retinopathy. More advanced grades of retinopathy are likely to be detected earlier with red-free imaging because of its better ability to detect IRMA, NVE, and NVD. Red-free monochromatic imaging of the retina is a more effective and less costly alternative for detection of vision-threatening diabetic retinopathy. PMID:22961609

  4. Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus.

    PubMed

    Carpineto, P; Toto, L; Aloia, R; Ciciarelli, V; Borrelli, E; Vitacolonna, E; Di Nicola, M; Di Antonio, L; Mastropasqua, R

    2016-05-01

    PurposeTo study neuroretinal alterations in patients affected by type 2 diabetes with no diabetic retinopathy (DR) or mild nonproliferative diabetic retinopathy (NPDR) and without any sign of diabetic macular edema.Patients and methodsIn total, 150 type 2 diabetic patients with no (131 eyes) or mild NPDR (19 eyes) and 50 healthy controls were enrolled in our study. All underwent a complete ophthalmologic examination, including Spectral-Domain optical coherence tomography (SD-OCT). Ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thickness values were calculated after automated segmentation of SD-OCT scans.ResultsMean best-corrected visual acuity was 0.0±0.0 LogMAR in all the groups. Mean GC-IPL thickness was 80.6±8.1 μm in diabetic patients and 85.3±9.9 μm in healthy controls, respectively (P=0.001). Moreover, evaluating the two different diabetic groups, GC-IPL thickness was 80.7±8.1 μm and 79.7±8.8 μm in no-DR and mild-NPDR group (P=0.001 and P=0.022 compared with healthy controls, respectively). Average RNFL thickness was 86.1±10.1 μm in diabetes patients and 91.2±7.3 μm in controls, respectively (P=0.003). RNFL thickness was 86.4±10.2 μm in no-DR group and 84.1±9.4 μm in mild-NPDR group (P=0.007 and P=0.017 compared with healthy controls, respectively).ConclusionWe demonstrated a significantly reduced GC-IPL and RNFL thickness values in both no-DR and mild-NPDR groups compared with healthy controls. These data confirmed neuroretinal alterations are early in diabetes, preceding microvascular damages. PMID:26869156

  5. Current trends in the pharmacotherapy of diabetic retinopathy.

    PubMed

    Kumar, B; Gupta, S K; Saxena, R; Srivastava, S

    2012-01-01

    Diabetic retinopathy (DR) is one of the most debilitating disorders of microvasculature of the retina and one of the leading causes of vision loss among the working class worldwide. At present, intravitreal anti-inflammatory (corticosteroids) and anti-angiogenesis (anti-Vascular Endothelial Growth Factor) agents are being used as wide options for the pharmacotherapy of DR and diabetic macular edema (DME). Anti-inflammatory agents (Triamcinolone acetonide and other agents) have shown evidence-based clinical benefits in various randomized clinical trials for the treatment of DR and DME, and also shown improvement in best corrected visual acuity. However, direct intravitreal injections are associated with serious side-effects like cataract and elevation of Intra Ocular Pressure. Despite this, corticosteroid therapy has been effective for DR and DME, therefore current focus is on the development of novel intravitreal steroid delivery devices that release a small quantity over a prolonged period of time. In addition to corticosteroids, anti-angiogenic agents are found to be effective for the treatment of DR and DME. The most popular target of these agents is the subfamily of proteins known as VEGF, whose over-expression is believed to play a role in numerous diseases including DR and Age-related Macular Degeneration. Intravitreal bevacizumab (Avastin®) and Ranibizumab (Lucentis®) are gaining popularity as a clinical adjunct to panretinal photocoagulation in patients with proliferative DR. Moreover, Lucentis has been recently approved by the United States Food and Drug Administration for macular edema following retinal vein occlusion. Further, systemic agents (specially, hypoglycemic, hypolipidemic and anti-hypertensive agents) have shown beneficial results in reducing the progression of DR. In conclusion, it can be stated that for the present scenario systematic use of available pharmacotherapy as an adjunct to laser photocoagulation, which is gold standard therapy

  6. Nrf2 as molecular target for polyphenols: A novel therapeutic strategy in diabetic retinopathy.

    PubMed

    Nabavi, Seyed Fazel; Barber, Alistair J; Spagnuolo, Carmela; Russo, Gian Luigi; Daglia, Maria; Nabavi, Seyed Mohammad; Sobarzo-Sánchez, Eduardo

    2016-10-01

    Diabetic retinopathy is a microvascular complication of diabetes that is considered one of the leading causes of blindness among adults. More than 4.4 million people suffer from this disorder throughout the world. Growing evidence suggests that oxidative stress plays a crucial role in the pathophysiology of diabetic retinopathy. Nuclear factor erythroid 2-related factor 2 (Nrf2), a redox sensitive transcription factor, plays an essential protective role in regulating the physiological response to oxidative and electrophilic stress via regulation of multiple genes encoding antioxidant proteins and phase II detoxifying enzymes. Many studies suggest that dozens of natural compounds, including polyphenols, can supress oxidative stress and inflammation through targeting Nrf2 and consequently activating the antioxidant response element-related cytoprotective genes. Therefore, Nrf2 may provide a new therapeutic target for treatment of diabetic retinopathy. In the present article, we will focus on the role of Nrf2 in diabetic retinopathy and the ability of polyphenols to target Nrf2 as a therapeutic strategy. PMID:26926494

  7. Serum insulin-like growth factor-I in diabetic retinopathy

    PubMed Central

    Tangpricha, Vin; Cleveland, Julia; Lynn, Michael J.; Ray, Robin; Srivastava, Sunil K.

    2011-01-01

    Purpose To assess the relationship between serum insulin-like growth factor I (IGF-I) and diabetic retinopathy. Methods This was a clinic-based cross-sectional study conducted at the Emory Eye Center. A total of 225 subjects were classified into four groups, based on diabetes status and retinopathy findings: no diabetes mellitus (no DM; n=99), diabetes with no background diabetic retinopathy (no BDR; n=42), nonproliferative diabetic retinopathy (NPDR; n=41), and proliferative diabetic retinopathy (PDR; n=43). Key exclusion criteria included type 1 diabetes and disorders that affect serum IGF-I levels, such as acromegaly. Subjects underwent dilated fundoscopic examination and were tested for hemoglobin A1c, serum creatinine, and serum IGF-I, between December 2009 and March 2010. Serum IGF-I levels were measured using an immunoassay that was calibrated against an international standard. Results Between the groups, there were no statistical differences with regards to age, race, or sex. Overall, diabetic subjects had similar serum IGF-I concentrations compared to nondiabetic subjects (117.6 µg/l versus 122.0 µg/l; p=0.497). There was no significant difference between serum IGF-I levels among the study groups (no DM=122.0 µg/l, no BDR=115.4 µg/l, NPDR=118.3 µg/l, PDR=119.1 µg/l; p=0.897). Among the diabetic groups, the mean IGF-I concentration was similar between insulin-dependent and non-insulin-dependent subjects (116.8 µg/l versus 118.2 µg/l; p=0.876). The univariate analysis of the IGF-I levels demonstrated statistical significance in regard to age (p=0.002, r=-0.20), body mass index (p=0.008, r=−0.18), and race (p=0.040). Conclusions There was no association between serum IGF-I concentrations and diabetic retinopathy in this large cross-sectional study. PMID:21921983

  8. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

    PubMed

    Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

    2016-05-10

    Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications. PMID:27114552

  9. A novel image recuperation approach for diagnosing and ranking retinopathy disease level using diabetic fundus image.

    PubMed

    Krishnamoorthy, Somasundaram; Alli, P

    2015-01-01

    Retinal fundus images are widely used in diagnosing and providing treatment for several eye diseases. Prior works using retinal fundus images detected the presence of exudation with the aid of publicly available dataset using extensive segmentation process. Though it was proved to be computationally efficient, it failed to create a diabetic retinopathy feature selection system for transparently diagnosing the disease state. Also the diagnosis of diseases did not employ machine learning methods to categorize candidate fundus images into true positive and true negative ratio. Several candidate fundus images did not include more detailed feature selection technique for diabetic retinopathy. To apply machine learning methods and classify the candidate fundus images on the basis of sliding window a method called, Diabetic Fundus Image Recuperation (DFIR) is designed in this paper. The initial phase of DFIR method select the feature of optic cup in digital retinal fundus images based on Sliding Window Approach. With this, the disease state for diabetic retinopathy is assessed. The feature selection in DFIR method uses collection of sliding windows to obtain the features based on the histogram value. The histogram based feature selection with the aid of Group Sparsity Non-overlapping function provides more detailed information of features. Using Support Vector Model in the second phase, the DFIR method based on Spiral Basis Function effectively ranks the diabetic retinopathy diseases. The ranking of disease level for each candidate set provides a much promising result for developing practically automated diabetic retinopathy diagnosis system. Experimental work on digital fundus images using the DFIR method performs research on the factors such as sensitivity, specificity rate, ranking efficiency and feature selection time. PMID:25974230

  10. A Novel Image Recuperation Approach for Diagnosing and Ranking Retinopathy Disease Level Using Diabetic Fundus Image

    PubMed Central

    2015-01-01

    Retinal fundus images are widely used in diagnosing and providing treatment for several eye diseases. Prior works using retinal fundus images detected the presence of exudation with the aid of publicly available dataset using extensive segmentation process. Though it was proved to be computationally efficient, it failed to create a diabetic retinopathy feature selection system for transparently diagnosing the disease state. Also the diagnosis of diseases did not employ machine learning methods to categorize candidate fundus images into true positive and true negative ratio. Several candidate fundus images did not include more detailed feature selection technique for diabetic retinopathy. To apply machine learning methods and classify the candidate fundus images on the basis of sliding window a method called, Diabetic Fundus Image Recuperation (DFIR) is designed in this paper. The initial phase of DFIR method select the feature of optic cup in digital retinal fundus images based on Sliding Window Approach. With this, the disease state for diabetic retinopathy is assessed. The feature selection in DFIR method uses collection of sliding windows to obtain the features based on the histogram value. The histogram based feature selection with the aid of Group Sparsity Non-overlapping function provides more detailed information of features. Using Support Vector Model in the second phase, the DFIR method based on Spiral Basis Function effectively ranks the diabetic retinopathy diseases. The ranking of disease level for each candidate set provides a much promising result for developing practically automated diabetic retinopathy diagnosis system. Experimental work on digital fundus images using the DFIR method performs research on the factors such as sensitivity, specificity rate, ranking efficiency and feature selection time. PMID:25974230

  11. Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response.

    PubMed

    Cui, Bei; Sun, Jin-Hua; Xiang, Fen-Fen; Liu, Lin; Li, Wen-Jie

    2012-05-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Diabetes is known to alter the amount of retinal expression of the water-selective channels aquaporin 4 (AQP4). However, the function and impact of AQP4 in diabetic retinopathy is not well understood. In the present work, diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Two weeks later, AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were delivered by intravitreal injection to the eyes. Gene delivery was confirmed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting analysis. Eight weeks later, BRB breakdown was measured using Evans blue dye. Images of retinal sections were obtained and the thicknesses of the retinas were determined. Retinal leukostasis measurement was performed using acridine orange leukocyte fluorography. The mRNA levels of IL-1β, IL-6, intercellular adhesion molecule 1 (ICAM-1), glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined using qRT-PCR method. AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were transfected into rMC-1 cells to investigate its effect on inflammation induced by high glucose. Incubation with IL-1β or IL-6 was performed to test their effect on AQP4 expression in rMC-1 cells. In the current work, it was found that AQP4 expression was enhanced in the retina of diabetic rats. AQP4 knockdown led to exacerbation of retinopathy including enhancing retinal vascular permeability, retinal thickness, pro-inflammatory factors expression, and VEGF and GFAP expression in retinas of diabetic rats. AQP4 knockdown enhanced the expression of pro-inflammatory cytokines induced by high glucose in rMC-1 cells. In addition, AQP4 knockdown enhanced the release of IL-6 and VEGF from rMC-1 cells into the medium. Moreover, it was found that incubation with IL-1β or IL-6 suppressed AQP4

  12. The Prize Is Healthy Eyes: Using Games to Educate about Diabetic Retinopathy

    ERIC Educational Resources Information Center

    Stastny, Sherri N.; Garden-Robinson, Julie

    2013-01-01

    This article describes a program for prevention of diabetic retinopathy (DR) that was designed for Extension in collaboration with optometrists. The program was created to increase knowledge and awareness about risk factors for DR and included a game and take-home materials. Participants were asked to play a game similar to Wheel of Fortune. A…

  13. Florida Model Task Force on Diabetic Retinopathy: Development of an Interagency Network.

    ERIC Educational Resources Information Center

    Groff, G.; And Others

    1990-01-01

    This article describes the development of a mechanism to organize a network in Florida for individuals who are at risk for diabetic retinopathy. The task force comprised representatives from governmental, academic, professional, and voluntary organizations. It worked to educate professionals, patients, and the public through brochures, resource…

  14. APOLIPOPROTEIN E GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH DIABETIC RETINOPATHY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

  15. Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats

    PubMed Central

    Chen, Wen-Pei; Wang, Yan-Dong; Ma, Yan; Zhang, Zi-Yang; Hu, Lu-Yun; Lin, Jun-Li; Lin, Bao-Qin

    2015-01-01

    AIM To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms. METHODS ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism. PMID:26682154

  16. Molecular Mechanism of Transcriptional Regulation of Matrix Metalloproteinase-9 in Diabetic Retinopathy.

    PubMed

    Mishra, Manish; Flaga, Jadwiga; Kowluru, Renu A

    2016-08-01

    Increase in matrix metalloproteinase-9 (MMP-9) is implicated in retinal capillary cell apoptosis, a phenomenon which precedes the development of diabetic retinopathy. MMP-9 promoter has multiple sites for binding the transcriptional factors, including two for activator protein 1 (AP-1). The binding of AP-1, a heterodimer of c-Jun and c-Fos, is regulated by posttranslational modifications, and in diabetes, deacetylating enzyme, Sirt1, is inhibited. Our aim, is to investigate the molecular mechanism of MMP-9 transcriptional regulation in diabetes. Binding of AP-1 (c-Jun, c-Fos) at the MMP-9 promoter, and AP-1 acetylation were analyzed in retinal endothelial cells incubated in normal or high glucose by chromatin-immunoprecipitation and co-immunoprecipitation respectively. Role of AP-1 in MMP-9 regulation was confirmed by c-Jun or c-Fos siRNAs, and that of its acetylation, by Sirt1 overexpression. In vitro results were validated in the retina from diabetic mice overexpressing Sirt1, and in the retinal microvessels from human donors with diabetic retinopathy. In experimental models, AP-1 binding was increased at the proximal and distal sites of the MMP-9 promoter, and similar phenomenon was confirmed in the retinal microvessels from human donors with diabetic retinopathy. Silencing of AP-1, or overexpression of Sirt1 ameliorated glucose-induced increase in MMP-9 expression and cell apoptosis. Thus, in diabetes, due to Sirt1 inhibition, AP-1 is hyperacetylated, which increases its binding at MMP-9 promoter, and hence, activation of Sirt1 could inhibit the development of diabetic retinopathy by impeding MMP-9-mediated mitochondrial damage. J. Cell. Physiol. 231: 1709-1718, 2016. © 2015 Wiley Periodicals, Inc. PMID:26599598

  17. The effect of vascular endothelial growth factor in the progression of bladder cancer and diabetic retinopathy

    PubMed Central

    Aldebasi, Yousef H; Rahmani, Arshad H; Khan, Amjad A; Aly, Salah Mesalhy

    2013-01-01

    Bladder cancer and diabetic retinopathy is a major public health and economical burden worldwide. Despite its high prevalence, the molecular mechanisms that induce or develop bladder carcinomas and diabetic retinopathy progression are poorly understood but it might be due to the disturbance in balance between angiogenic factors such as VEGF and antiangiogenic factors such as pigment epithelium derived growth factor. VEGF is one of the important survival factors for endothelial cells in the process of normal physiological and abnormal angiogenesis and induce the expression of antiapoptotic proteins in the endothelial cells. It is also the major initiator of angiogenesis in cancer and diabetic retinopathy, where it is up-regulated by oncogenic expression and different type of growth factors. The alteration in VEGF and VEGF receptors gene and overexpression, determines a diseases phenotype and ultimately the patient’s clinical outcome. However, expressional and molecular studies were made on VEGF to understand the exact mechanism of action in the genesis and progression of bladder carcinoma and diabetic retinopathy , but still how VEGF mechanism involve in such type of disease progression are not well defined. Some other factors also play a significant role in the process of activation of VEGF pathways. Therefore, further detailed analysis via molecular and therapeutic is needed to know the exact mechanisms of VEGF in the angiogenesis pathway. The detection of these types of diseases at an early stage, predict how it will behave and act in response to treatment through regulation of VEGF pathways. The present review aimed to summarize the mechanism of alteration of VEGF gene pathways, which play a vital role in the development and progression of bladder cancer and diabetic retinopathy. PMID:23641300

  18. Could donor multipotent mesenchymal stromal cells prevent or delay the onset of diabetic retinopathy?

    PubMed

    Ezquer, Fernando; Ezquer, Marcelo; Arango-Rodriguez, Martha; Conget, Paulette

    2014-03-01

    Diabetes mellitus is a complex metabolic disease that has become a global epidemic with more than 285 million cases worldwide. Major medical advances over the past decades have substantially improved its management, extending patients' survival. The latter is accompanied by an increased risk of developing chronic macro- and microvascular complications. Amongst them, diabetic retinopathy (DR) is the most common and frightening. Furthermore, during the past two decades, it has become the leading cause of visual loss. Irrespective of the type of diabetes, DR follows a well-known clinical and temporal course characterized by pericytes and neuronal cell loss, formation of acellular-occluded capillaries, occasional microaneurysms, increased leucostasis and thickening of the vascular basement membrane. These alterations progressively affect the integrity of retinal microvessels, leading to the breakdown of the blood-retinal barrier, widespread haemorrhage and neovascularization. Finally, tractional retinal detachment occurs leading to blindness. Nowadays, there is growing evidence that local inflammation and oxidative stress play pivotal roles in the pathogenesis of DR. Both processes have been associated with pericytes and neuronal degeneration observed early during DR progression. They may also be linked to sustained retinal vasculature damage that results in abnormal neovascularization. Currently, DR therapeutic options depend on highly invasive surgical procedures performed only at advanced stages of the disease, and which have proved to be ineffective to restore visual acuity. Therefore, the availability of less invasive and more effective strategies aimed to prevent or delay the onset of DR is highly desirable. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), are promising healing agents as they contribute to tissue regeneration by pleiotropic mechanisms, with no evidence of significant adverse events. Here, we revise the

  19. The Cross-sectional and Longitudinal Associations of Diabetic Retinopathy With Cognitive Function and Brain MRI Findings: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

    PubMed Central

    Lovato, James F.; Ambrosius, Walter T.; Bryan, R. Nick; Gerstein, Hertzel C.; Horowitz, Karen R.; Launer, Lenore J.; Lazar, Ronald M.; Murray, Anne M.; Chew, Emily Y.; Danis, Ronald P.; Williamson, Jeff D.; Miller, Michael E.; Ding, Jingzhong

    2014-01-01

    OBJECTIVE Longitudinal evidence linking diabetic retinopathy with changes in brain structure and cognition is sparse. We used data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to determine whether diabetic retinopathy at baseline predicted changes in brain structure or cognition 40 months later. RESEARCH DESIGN AND METHODS Participants from the ACCORD-MIND and ACCORD-Eye substudies were included in analyses of cognition (n = 1,862) and MRI-derived brain variables (n = 432). Retinopathy was categorized as none, mild nonproliferative, or moderate/severe. Tests of cognition included the Mini-Mental State Examination (MMSE), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test, and Stroop test. Primary brain outcomes were gray matter and abnormal white matter volumes. RESULTS Baseline retinopathy was associated with lower gray matter volume (adjusted means of 470, 466, and 461 cm3 for none, mild, and moderate/severe retinopathy, respectively; P = 0.03). Baseline retinopathy also predicted a greater change in MMSE and DSST scores at 40 months in each retinopathy category (MMSE: −0.20, −0.57, and −0.42, respectively [P = 0.04]; DSST: −1.30, −1.84, and −2.89, respectively[P = 0.01]). CONCLUSIONS Diabetic retinopathy is associated with future cognitive decline in people with type 2 diabetes. Although diabetic retinopathy is not a perfect proxy for diabetes-related brain and cognitive decline, patients with type 2 diabetes and retinopathy represent a subgroup at higher risk for future cognitive decline. PMID:25193529

  20. Increased Vitreous Shedding of Microparticles in Proliferative Diabetic Retinopathy Stimulates Endothelial Proliferation

    PubMed Central

    Chahed, Sadri; Leroyer, Aurélie S.; Benzerroug, Mounir; Gaucher, David; Georgescu, Adriana; Picaud, Serge; Silvestre, Jean-Sébastien; Gaudric, Alain; Tedgui, Alain; Massin, Pascale; Boulanger, Chantal M.

    2010-01-01

    OBJECTIVE Diabetic retinopathy is associated with progressive retinal capillary activation and proliferation, leading to vision impairment and blindness. Microparticles are submicron membrane vesicles with biological activities, released following cell activation or apoptosis. We tested the hypothesis that proangiogenic microparticles accumulate in vitreous fluid in diabetic retinopathy. RESEARCH DESIGN AND METHODS Levels and cellular origin of vitreous and plasma microparticles from control (n = 26) and diabetic (n = 104) patients were analyzed by flow cytometry, and their proangiogenic activity was assessed by in vitro thymidine incorporation and neovessel formation in subcutaneous Matrigel plugs in mice. RESULTS Microparticles of endothelial, platelet, photoreceptor, and microglial origin were identified in vitreous samples. Levels of photoreceptor and microglial microparticles were undetectable in plasmas but were comparable in diabetic and control vitreous samples. Vitreous platelet and endothelial microparticles levels were increased in diabetic patients and decreased following panretinal laser photocoagulation or intravitreal antivascular endothelial growth factor injection in proliferative diabetic retinopathy (PDR). The ratio of vitreous to plasma microparticle levels was calculated to estimate local formation versus potential plasma leakage. In PDR, the endothelial microparticles ratio—but not that for platelet—was greater than 1.0, indicating local formation of endothelial microparticles from retinal vessels and permeation of platelet microparticles from plasma. Isolated vitreous microparticles stimulated by 1.6-fold endothelial proliferation and increased new vessel formation in mice. CONCLUSIONS The present study demonstrates that vitreous fluid contains shed membrane microparticles of endothelial, platelet, and retinal origin. Vitreous microparticles levels are increased in patients with diabetic retinopathy, where they could contribute to disease

  1. Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy

    PubMed Central

    Keppel Hesselink, Jan M.; Costagliola, Ciro; Fakhry, Josiane; Kopsky, David J.

    2015-01-01

    Retinopathy is a threat to the eyesight, and glaucoma and diabetes are the main causes for the damage of retinal cells. Recent insights pointed out a common pathogenetic pathway for both disorders, based on chronic inflammation. Palmitoylethanolamide (PEA) is an endogenous cell protective lipid. Since its discovery in 1957 as a biologically active component in foods and in many living organisms, around 500 scientific papers have been published on PEA's anti-inflammatory and neuron-protective properties. PEA has been evaluated for glaucoma, diabetic retinopathy, and uveitis, pathological states based on chronic inflammation, respiratory disorders, and various pain syndromes in a number of clinical trials since the 70s of 20th century. PEA is available as a food supplement (PeaPure) and as diet food for medical purposes in Italy (Normast, PeaVera, and Visimast). These products are notified in Italy for the nutritional support in glaucoma and neuroinflammation. PEA has been tested in at least 9 double blind placebo controlled studies, among which two studies were in glaucoma, and found to be safe and effective up to 1.8 g/day, with excellent tolerability. PEA therefore holds a promise in the treatment of a number of retinopathies. We discuss PEA as a putative anti-inflammatory and retinoprotectant compound in the treatment of retinopathies, especially related to glaucoma and diabetes. PMID:26664738

  2. Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy.

    PubMed

    Keppel Hesselink, Jan M; Costagliola, Ciro; Fakhry, Josiane; Kopsky, David J

    2015-01-01

    Retinopathy is a threat to the eyesight, and glaucoma and diabetes are the main causes for the damage of retinal cells. Recent insights pointed out a common pathogenetic pathway for both disorders, based on chronic inflammation. Palmitoylethanolamide (PEA) is an endogenous cell protective lipid. Since its discovery in 1957 as a biologically active component in foods and in many living organisms, around 500 scientific papers have been published on PEA's anti-inflammatory and neuron-protective properties. PEA has been evaluated for glaucoma, diabetic retinopathy, and uveitis, pathological states based on chronic inflammation, respiratory disorders, and various pain syndromes in a number of clinical trials since the 70s of 20th century. PEA is available as a food supplement (PeaPure) and as diet food for medical purposes in Italy (Normast, PeaVera, and Visimast). These products are notified in Italy for the nutritional support in glaucoma and neuroinflammation. PEA has been tested in at least 9 double blind placebo controlled studies, among which two studies were in glaucoma, and found to be safe and effective up to 1.8 g/day, with excellent tolerability. PEA therefore holds a promise in the treatment of a number of retinopathies. We discuss PEA as a putative anti-inflammatory and retinoprotectant compound in the treatment of retinopathies, especially related to glaucoma and diabetes. PMID:26664738

  3. Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework

    NASA Astrophysics Data System (ADS)

    Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin

    2013-02-01

    Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

  4. Novel pharmacotherapies in diabetic retinopathy: Current status and what's in the horizon?

    PubMed Central

    Das, Arup; McGuire, Paul G; Monickaraj, Finny

    2016-01-01

    The blood–retinal barrier (BRB) alteration is the hallmark feature of diabetic retinopathy. Vascular endothelial growth factor (VEGF) is a potent vasopermeability factor that has been implicated in the pathogenesis of BRB alteration. Inflammation also plays a crucial role in this process with involvement of several chemokines and cytokines. Multiple anti-VEGF drugs are widely used as in the treatment of diabetic macular edema (DME) as well as proliferative diabetic retinopathy. Several clinical trials have proved the beneficial effects of these drugs in improvement of vision and prevention of vision loss. However, the response to anti-VEGF drugs in DME is not complete in a significant number of patients. The effect seems transient in this latter group, and many patients do not show complete resolution of fluid. Potential novel therapies targeting molecules beyond VEGF are being developed and examined in clinical trials. PMID:26953018

  5. Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with Diabetic Retinopathy

    PubMed Central

    Crosby-Nwaobi, Roxanne; Chatziralli, Irini; Sergentanis, Theodoros; Dew, Tracy; Forbes, Angus; Sivaprasad, Sobha

    2015-01-01

    Purpose. The purpose of this study was to examine the relationship between metabolic and inflammatory markers in patients with diabetic retinopathy (DR). Methods. 208 adult patients with type 2 diabetes participated in this study and were categorized into (1) mild nonproliferative diabetic retinopathy (NPDR) without clinically significant macular edema (CSME), (2) NPDR with CSME, (3) proliferative diabetic retinopathy (PDR) without CSME, and (4) PDR with CSME. Variable serum metabolic markers were assessed using immunoassays. Multinomial logistic regression analysis was performed. Results. Diabetes duration and hypertension are the most significant risk factors for DR. Serum Apo-B and Apo-B/Apo-A ratio were the most significant metabolic risk factors for PDR and CSME. For every 0.1 g/L increase in Apo-B concentration, the risk of PDR and CSME increased by about 1.20 times. We also found that 10 pg/mL increase in serum TNF-α was associated with approximately 2-fold risk of PDR/CSME while an increase by 100 pg/mL in serum VEGF concentration correlated with CSME. Conclusions. In conclusion, it seems that there is a link between metabolic and inflammatory markers. Apo-B/Apo-A ratio should be evaluated as a reliable risk factor for PDR and CSME, while the role of increased systemic TNF-α and VEGF should be explored in CSME. PMID:26295054

  6. Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

    PubMed

    Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

    2016-04-01

    Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. PMID:26740595

  7. Digital Algorithmic Diabetic Retinopathy Severity Scoring System (An American Ophthalmological Society Thesis)

    PubMed Central

    Slakter, Jason S.; Schneebaum, Jeffrey W.; Shah, Sabah A.

    2015-01-01

    Purpose: To develop a new diabetic retinopathy severity scoring system and to determine if it can monitor changes from baseline as well as identify precise features that have changed over time. Such a grading system could potentially provide an understanding of the impact of treatments utilizing an algorithmic scoring technique. Methods: The traditional ETDRS grading system was examined and a flow algorithm based on the grading approach was created. All visual comparative assessment points, relying on identification of features in relation to prior standard photographic images, were evaluated and quantified. A new grading form was created that provided fields that captured all relevant features required for determining the ETDRS grading score. A computer software algorithm was developed that examines all entered fields and calculates the appropriate diabetic severity score. Results: This diabetic retinopathy scoring algorithm system was successful in generating a severity score comparable to traditional methods of grading images. Validation with traditionally graded images was performed, demonstrating that in a majority of cases, the severity scores were comparable. The algorithmic grading system was then used to analyze images obtained in a large clinical study of diabetic macular edema, resulting in data regarding baseline scoring values, as well as detailed features of the microvasculature that drove the severity scoring results, and changes seen during the trial. Conclusion: This new algorithmic diabetic severity scoring system provides a means to monitor the progression or regression of retinopathy with therapeutic intervention as well as assess the individual microvascular features that may be modified over the course of treatment.

  8. Summarising the retinal vascular calibres in healthy, diabetic and diabetic retinopathy eyes.

    PubMed

    Leontidis, Georgios; Al-Diri, Bashir; Hunter, Andrew

    2016-05-01

    Retinal vessel calibre has been found to be an important biomarker of several retinal diseases, including diabetic retinopathy (DR). Quantifying the retinal vessel calibres is an important step for estimating the central retinal artery and vein equivalents. In this study, an alternative method to the already established branching coefficient (BC) is proposed for summarising the vessel calibres in retinal junctions. This new method combines the mean diameter ratio with an alternative to Murray׳s cube law exponent, derived by the fractal dimension,experimentally, and the branch exponent of cerebral vessels, as has been suggested in previous studies with blood flow modelling. For the above calculations, retinal images from healthy, diabetic and DR subjects were used. In addition, the above method was compared with the BC and was also applied to the evaluation of arteriovenous ratio as a biomarker of progression from diabetes to DR in four consecutive years, i.e. three/two/one years before the onset of DR and the first year of DR. Moreover, the retinal arteries and veins around the optic nerve head were also evaluated. The new approach quantifies the vessels more accurately. The decrease in terms of the mean absolute percentage error was between 0.24% and 0.49%, extending at the same time the quantification beyond healthy subjects. PMID:27017067

  9. Frequency, severity and risk indicators of retinopathy in patients with diabetes screened by fundus photographs: a study from primary health care

    PubMed Central

    Memon, Saleh; Ahsan, Shahid; Riaz, Qamar; Basit, Abdul; Ali Sheikh, Sikandar; Fawwad, Asher; Shera, A Samad

    2014-01-01

    Objective: To determine the frequency, severity and risk indicators of diabetic retinopathy (DR) in patients with diabetes attending a primary care diabetes centre. Methods: This observational study was conducted at Diabetic Association of Pakistan - a World Health Organization collaborating center in Karachi, from March 2009 to December 2011. Registered patients with diabetes were screened by two field fundus photographs. Retina specialists graded the signs of retinopathy according to diabetic retinopathy disease severity scale. Results: Of total registered diabetic patients (n=11,158), 10,768 (96.5 %) were screened for DR. Overall DR was found in 2661 (24.7%) patients. DR was found in decreasing order of frequency in patients with type 2 (n= 2555, 23.7%) followed by patients with type 1 diabetes (n=101, 0.93% ) and patients with gestational diabetes mellitus (GDM) (n=5, 0.46%). Among patients with DR, signs of non-sight threatening retinopathy was dominant. Females and patients of working age group predominantly had retinopathy. Type 1 patients >16 years and type 2 patients < 5 years of history of diabetes had sign of retinopathy in increased frequency. Conclusion: Every forth patient with diabetes in this large cohort had signs of diabetic retinopathy. Females and patients in working age group predominantly had retinopathy. Type 2 patients with short while type 1 patients with long history of diabetes most frequently had DR. Dissemination of the present study findings may help in increasing the awareness of this serious complication of diabetes. PMID:24772145

  10. Epigenetic Modification of Mitochondrial DNA in the Development of Diabetic Retinopathy

    PubMed Central

    Mishra, Manish; Kowluru, Renu A.

    2015-01-01

    Purpose Retinal mitochondria are dysfunctional in diabetes, and mitochondrial DNA (mtDNA) is damaged and its transcription is compromised. Our aim was to investigate the role of mtDNA methylation in the development of diabetic retinopathy. Methods Effect of high glucose (20 mM) on mtDNA methylation was analyzed in retinal endothelial cells by methylation-specific PCR and by quantifying 5-methylcytosine (5mC). Dnmt1 binding at the D-loop and Cytb regions of mtDNA was analyzed by chromatin immunoprecipitation. The role of mtDNA methylation in transcription and cell death was confirmed by quantifying transcripts of mtDNA-encoded genes (Cytb, ND6, and CoxII) and apoptosis, using cells transfected with Dnmt1-small interfering RNA (siRNA), or incubated with a Dnmt inhibitor. The key parameters were validated in the retinal microvasculature from human donors with diabetic retinopathy. Results High glucose increased mtDNA methylation, and methylation was significantly higher at the D-loop than at the Cytb and CoxII regions. Mitochondrial accumulation of Dnmt1 and its binding at the D-loop were also significantly increased. Inhibition of Dnmt by its siRNA or pharmacologic inhibitor ameliorated glucose-induced increase in 5mC levels and cell apoptosis. Retinal microvasculature from human donors with diabetic retinopathy presented similar increase in D-loop methylation and decrease in mtDNA transcription. Conclusions Hypermethylation of mtDNA in diabetes impairs its transcription, resulting in dysfunctional mitochondria and accelerated capillary cell apoptosis. Regulation of mtDNA methylation has potential to restore mitochondrial homeostasis and inhibit/retard the development of diabetic retinopathy. PMID:26241401

  11. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy

    PubMed Central

    Rahimi, Zohreh; Moradi, Mahmoudreza; Nasri, Hamid

    2014-01-01

    Background: The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD). Materials and Methods: The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR), diabetic neuropathy and cardiovascular complication of DM. Results: The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT) M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene (AT1R) A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients. Conclusion: More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications. PMID:25657757

  12. Does tight control of systemic factors help in the management of diabetic retinopathy?

    PubMed Central

    Rajalakshmi, Ramachandran; Prathiba, Vijayaraghavan; Mohan, Viswanathan

    2016-01-01

    Diabetic retinopathy (DR), one of the leading causes of preventable blindness, is associated with many systemic factors that contribute to the development and progression of this microvascular complication of diabetes. While the duration of diabetes is the major risk factor for the development of DR, the main modifiable systemic risk factors for development and progression of DR are hyperglycemia, hypertension, and dyslipidemia. This review article looks at the evidence that control of these systemic factors has significant benefits in delaying the onset and progression of DR. PMID:26953026

  13. Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice.

    PubMed

    Dominguez, James M; Hu, Ping; Caballero, Sergio; Moldovan, Leni; Verma, Amrisha; Oudit, Gavin Y; Li, Qiuhong; Grant, Maria B

    2016-06-01

    Angiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections. Retinal digestion using trypsin was performed and acellular capillaries enumerated. Capillary occlusion by GFP(+) cells was used to measure leukostasis. Overexpression of ACE2 prevented (prevention cohort: untreated diabetic, 11.3 ± 1.4; ACE2 diabetic, 6.4 ± 0.9 per mm(2)) and partially reversed (reversal cohort: untreated diabetic, 15.7 ± 1.9; ACE2 diabetic, 6.5 ± 1.2 per mm(2)) the diabetes-associated increase of acellular capillaries and the increase of infiltrating inflammatory cells into the retina (F4/80(+)) (prevention cohort: untreated diabetic, 24.2 ± 6.7; ACE2 diabetic, 2.5 ± 1.6 per mm(2); reversal cohort: untreated diabetic, 56.8 ± 5.2; ACE2 diabetic, 5.6 ± 2.3 per mm(2)). In both study cohorts, intracapillary bone marrow-derived cells, indicative of leukostasis, were only observed in diabetic animals receiving control AAV injections. These results indicate that diabetic retinopathy, and possibly other diabetic microvascular complications, can be prevented and reversed by locally restoring the balance between the classic and vasoprotective renin angiotensin system. PMID:27178803

  14. Cental Macular Thickness in Patients with Type 2 Diabetes Mellitus without Clinical Retinopathy.

    PubMed

    Demir, Mehmet; Dirim, Burcu; Acar, Zeynep; Yılmaz, Murat; Sendul, Yekta

    2013-01-01

    Objective. To compare central macular thickness (CMT) of diabetic patients with type 2 diabetes without clinical retinopathy and healthy subjects. Materials and Methods. Optical coherence tomography (OCT) measurements were performed in 124 eyes of 62 subjects with diabetes mellitus without clinical retinopathy (study group: 39 females, 23 males; mean age: 55.06 ± 9.77 years) and in 120 eyes of 60 healthy subjects (control group: 35 females, 25 males; mean age: 55.78 ± 10.34 years). Blood biochemistry parameters were analyzed in all cases. The data for central macular thickness (at 1 mm), the levels of fasting plasma glucose, and glycosylated hemoglobin (HbA1c) were compared in both groups. Results. The mean central macular thickness was 232.12 ± 24.41 µm in the study group and 227.19 ± 29.94 µm in the control group. The mean HbA1c level was 8.92 ± 2.58% in the study group and 5.07 ± 0.70% in the control group (P = 0.001). No statistically significant relationship was found between CMT, HbA1c, and fasting plasma glucose level in either group (P > 0.05). Conclusions. Central macular thickness was not significantly thicker in patients with type 2 diabetes without clinical retinopathy than in healthy subjects. PMID:23691279

  15. Intervention with vitamins in patients with nonproliferative diabetic retinopathy: a pilot study

    PubMed Central

    Smolek, Michael K; Notaroberto, Neil F; Jaramillo, Arley G; Pradillo, Lisa R

    2013-01-01

    Background The purpose of this study was to determine whether a combination of vitamins B6, B9, and B12 is an effective intervention for reducing the signs and symptoms of nonproliferative diabetic retinopathy. Methods Ten subjects with type 2 diabetes mellitus (n = 20 eyes) with clinically diagnosed mild to moderate nonproliferative diabetic retinopathy were recruited from a private practice ophthalmology clinic for this open-label, uncontrolled, prospective six-month study. Metanx® vitamin tablets (containing 3 mg L-methylfolate calcium, 35 mg pyridoxal-5′-phosphate, and 2 mg methylcobalamin) were administered at a dosage of two tablets daily. Primary outcome indicators were the percent change in mean retinal sensitivity threshold measured by macular microperimetry and the percent change in mean central retinal thickness measured by spectral-domain optical coherence tomography. Results Three subjects were lost to follow-up. In the remaining seven subjects, two of 14 eyes had foveal edema that prevented microperimetry measurements due to poor fixation. The remaining 12 eyes showed a nonlinear improvement in mean threshold retinal sensitivity (P < 0.001). Overall change in mean central retinal thickness in 14 eyes was linear (R2 = 0.625; P = 0.034), with a significant reduction between one and six months (P = 0.012). Conclusion In this pilot study, the Metanx intervention appeared to have some beneficial effects with respect to reducing retinal edema and increasing light sensitivity in subjects with nonproliferative diabetic retinopathy. PMID:23898220

  16. Clinical Decision Support for the Classification of Diabetic Retinopathy: A Comparison of Manual and Automated Results.

    PubMed

    Mitsch, Christoph; Fehre, Karsten; Prager, Sonja; Scholda, Christoph; Kriechbaum, Katharina; Wrba, Thomas; Schmidt-Erfurth, Ursula

    2016-01-01

    The management of diabetic retinopathy, a frequent ophthalmological manifestation of diabetes mellitus, consists of regular examinations and a standardized, manual classification of disease severity, which is used to recommend re-examination intervals. To evaluate the feasibility and safety of implementing automated, guideline-based diabetic retinopathy (DR) grading into clinical routine by applying established clinical decision support (CDS) technology. We compared manual with automated classification that was generated using medical documentation and an Arden server with a specific medical logic module. Of 7169 included eyes, 47% (n=3373) showed inter-method classification agreement, specifically 29.4% in mild DR, 38.3% in moderate DR, 27.6% in severe DR, and 65.7% in proliferative DR. We demonstrate that the implementation of a CDS system for automated disease severity classification in diabetic retinopathy is feasible but also that, due to the highly individual nature of medical documentation, certain important criteria for the used electronic health record system need to be met in order to achieve reliable results. PMID:27139380

  17. Evaluation of argon laser treatment of diabetic retinopathy and its diffusion in The Netherlands.

    PubMed

    Vondeling, H

    1993-01-01

    Argon laser treatment of diabetic retinopathy (DR) is the best evaluated case in the field of minimally invasive therapy. A well-organized randomized controlled trial was followed by formal cost-analyses and cost-effectiveness analyses. Laser treatment of DR proved to be cost-effective in a situation where there was no satisfactory treatment previously. Subsequently, screening strategies for retinopathy were developed. Systematic screening for DR in diabetic populations would be cost-saving from a societal perspective. The availability of effective and cost-effective therapy and cost-saving screening strategies for DR warrants active policy making to stimulate the implementation of strategies to control retinopathy in diabetic populations. Such strategies would ideally include both guided diffusion of argon lasers and the organization of screening programs. Data from the Netherlands are used to illustrate the diffusion of argon lasers in health care. After a slow start, argon lasers have diffused widely in the Dutch health care system. This development is complemented by recommendations for screening of the European diabetic population, which were issued in 1991. More active cooperation of all parties involved would benefit in preventing blindness from DR. PMID:10123418

  18. The Vanderbilt Classification System in the evaluation of diabetic retinopathy patients treated with Alredase.

    PubMed Central

    Feman, S S; Leonard-Martin, T C; Redman, J R

    1996-01-01

    BACKGROUND: The Vanderbilt Classification System is a quantitative method of measuring features detected in diabetic retinopathy photographs. It does not require comparisons to preexisting standard photographs. This is the first report of the application of this system to a large-scale, multiple-medical-center drug trial. METHODS: This was a prospective, randomized, double-masked, placebo-controlled study that involved 74 medical centers. There were 3,679 out-patients followed for more that 4 years, with some observed for over 9 years. The Vanderbilt Classification System generated patient data for the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetes Control and Complication Trial (DCCT) scales. The deterioration rate was one variable used to assess drug effect. A comprehensive Quality Assurance Program evaluated intergrader and intragrader reliability. RESULTS: Target values for reliability and reproducibility were met or exceeded on all measures of agreement between photo readers and over time. Kappa statistics were 0.610 or greater, with most weighted kappa values greater than 0.810. This represents "almost perfect agreement" and compares favorably with previous reports from the ETDRS and DCCT. CONCLUSION: Diabetic retinopathy can be evaluated in a reliable and reproducible manner with the VCS. The VCS is unique in that it produces a quantitative analysis of retinal lesions. Subtle variations that might be influenced by systemic medications can be measured accurately with this technique. PMID:8981708

  19. Diagnosing and Ranking Retinopathy Disease Level Using Diabetic Fundus Image Recuperation Approach

    PubMed Central

    Somasundaram, K.; Alli Rajendran, P.

    2015-01-01

    Retinal fundus images are widely used in diagnosing different types of eye diseases. The existing methods such as Feature Based Macular Edema Detection (FMED) and Optimally Adjusted Morphological Operator (OAMO) effectively detected the presence of exudation in fundus images and identified the true positive ratio of exudates detection, respectively. These mechanically detected exudates did not include more detailed feature selection technique to the system for detection of diabetic retinopathy. To categorize the exudates, Diabetic Fundus Image Recuperation (DFIR) method based on sliding window approach is developed in this work to select the features of optic cup in digital retinal fundus images. The DFIR feature selection uses collection of sliding windows with varying range to obtain the features based on the histogram value using Group Sparsity Nonoverlapping Function. Using support vector model in the second phase, the DFIR method based on Spiral Basis Function effectively ranks the diabetic retinopathy disease level. The ranking of disease level on each candidate set provides a much promising result for developing practically automated and assisted diabetic retinopathy diagnosis system. Experimental work on digital fundus images using the DFIR method performs research on the factors such as sensitivity, ranking efficiency, and feature selection time. PMID:25945362

  20. Adipose-Derived Stem Cells From Diabetic Mice Show Impaired Vascular Stabilization in a Murine Model of Diabetic Retinopathy

    PubMed Central

    Cronk, Stephen M.; Kelly-Goss, Molly R.; Ray, H. Clifton; Mendel, Thomas A.; Hoehn, Kyle L.; Bruce, Anthony C.; Dey, Bijan K.; Guendel, Alexander M.; Tavakol, Daniel N.; Herman, Ira M.; Yates, Paul A.

    2015-01-01

    Diabetic retinopathy is characterized by progressive vascular dropout with subsequent vision loss. We have recently shown that an intravitreal injection of adipose-derived stem cells (ASCs) can stabilize the retinal microvasculature, enabling repair and regeneration of damaged capillary beds in vivo. Because an understanding of ASC status from healthy versus diseased donors will be important as autologous cellular therapies are developed for unmet clinical needs, we took advantage of the hyperglycemic Akimba mouse as a preclinical in vivo model of diabetic retinopathy in an effort aimed at evaluating therapeutic efficacy of adipose-derived stem cells (mASCs) derived either from healthy, nondiabetic or from diabetic mice. To these ends, Akimba mice received intravitreal injections of media conditioned by mASCs or mASCs themselves, subsequent to development of substantial retinal capillary dropout. mASCs from healthy mice were more effective than diabetic mASCs in protecting the diabetic retina from further vascular dropout. Engrafted ASCs were found to preferentially associate with the retinal vasculature. Conditioned medium was unable to recapitulate the vasoprotection seen with injected ASCs. In vitro diabetic ASCs showed decreased proliferation and increased apoptosis compared with healthy mASCs. Diabetic ASCs also secreted less vasoprotective factors than healthy mASCs, as determined by high-throughput enzyme-linked immunosorbent assay. Our findings suggest that diabetic ASCs are functionally impaired compared with healthy ASCs and support the utility of an allogeneic injection of ASCs versus autologous or conditioned media approaches in the treatment of diabetic retinopathy. PMID:25769654

  1. Detection of retinal capillary nonperfusion in fundus fluorescein angiogram of diabetic retinopathy

    PubMed Central

    Rasta, Seyed Hossein; Nikfarjam, Shima; Javadzadeh, Alireza

    2015-01-01

    Introduction: Retinal capillary nonperfusion (CNP) is one of the retinal vascular diseases in diabetic retinopathy (DR) patients. As there is no comprehensive detection technique to recognize CNP areas, we proposed a different method for computing detection of ischemic retina, non-perfused (NP) regions, in fundus fluorescein angiogram (FFA) images. Methods: Whilst major vessels appear as ridges, non-perfused areas are usually observed as ponds that are surrounded by healthy capillaries in FFA images. A new technique using homomorphic filtering to correct light illumination and detect the ponds surrounded in healthy capillaries on FFA images was designed and applied on DR fundus images. These images were acquired from the diabetic patients who had referred to the Nikookari hospital and were diagnosed for diabetic retinopathy during one year. Our strategy was screening the whole image with a fixed window size, which is small enough to enclose areas with identified topographic characteristics. To discard false nominees, we also performed a thresholding operation on the screen and marked images. To validate its performance we applied our detection algorithm on 41 FFA diabetic retinopathy fundus images in which the CNP areas were manually delineated by three clinical experts. Results: Lesions were found as smooth regions with very high uniformity, low entropy, and small intensity variations in FFA images. The results of automated detection method were compared with manually marked CNP areas so achieved sensitivity of 81%, specificity of 78%, and accuracy of 91%.The result was present as a Receiver operating character (ROC) curve, which has an area under the curve (AUC) of 0.796 with 95% confidence intervals. Conclusion: This technique introduced a new automated detection algorithm to recognize non-perfusion lesions on FFA. This has potential to assist detecting and managing of ischemic retina and may be incorporated into automated grading diabetic retinopathy structures

  2. Diabetic Retinopathy Screening Ratio Is Improved When Using a Digital, Nonmydriatic Fundus Camera Onsite in a Diabetes Outpatient Clinic

    PubMed Central

    Roser, Pia; Kalscheuer, Hannes; Groener, Jan B.; Lehnhoff, Daniel; Klein, Roman; Auffarth, Gerd U.; Nawroth, Peter P.; Schuett, Florian; Rudofsky, Gottfried

    2016-01-01

    Objective. To evaluate the effect of onsite screening with a nonmydriatic, digital fundus camera for diabetic retinopathy (DR) at a diabetes outpatient clinic. Research Design and Methods. This cross-sectional study included 502 patients, 112 with type 1 and 390 with type 2 diabetes. Patients attended screenings for microvascular complications, including diabetic nephropathy (DN), diabetic polyneuropathy (DP), and DR. Single-field retinal imaging with a digital, nonmydriatic fundus camera was used to assess DR. Prevalence and incidence of microvascular complications were analyzed and the ratio of newly diagnosed to preexisting complications for all entities was calculated in order to differentiate natural progress from missed DRs. Results. For both types of diabetes, prevalence of DR was 25.0% (n = 126) and incidence 6.4% (n = 32) (T1DM versus T2DM: prevalence: 35.7% versus 22.1%, incidence 5.4% versus 6.7%). 25.4% of all DRs were newly diagnosed. Furthermore, the ratio of newly diagnosed to preexisting DR was higher than those for DN (p = 0.12) and DP (p = 0.03) representing at least 13 patients with missed DR. Conclusions. The results indicate that implementing nonmydriatic, digital fundus imaging in a diabetes outpatient clinic can contribute to improved early diagnosis of diabetic retinopathy. PMID:26904690

  3. Newly diagnosed diabetes mellitus patients presenting with proliferative diabetic retinopathy as an initial sign

    PubMed Central

    Park, Hoon; Kim, Young Gyun; Lee, Jong Wook; Park, Jong Seok

    2014-01-01

    AIM To investigate the clinical features of newly diagnosed diabetes mellitus (NDM) patients showing proliferative diabetic retinopathy (PDR) as an initial sign. METHODS As a retrospective case series, the medical records of a total of four hundred and thirty-two patients who underwent a vitrectomy due to PDR were reviewed to find the subjects. Of 432 patients, six cases of NDM patients showing PDR as an initial sign were included and analyzed with their systemic and ocular features. Main outcome measures: the systemic features and ocular features [preoperative and postoperative best corrected visual acuity (BCVA), intraoperative findings]. RESULTS The mean onset age of visual symptoms was 36.3 years old. The mean serum insulin and C-peptide titer was below the normal range. The mean fasting plasma glucose was 178mg/dL and the mean postprandial 2h plasma glucose was 306mg/dL. The mean HbA1c at diagnosis was 11.02%. In all cases, an acute progressive fibrovascular proliferation was observed. Intraoperative retinal tears were found in three cases of six. The mean preoperative BCVA was +0.67±0.58 logMAR and the mean BCVA at postoperative 6 months was +0.20±0.30 logMAR. CONCLUSION All patients were considered to have latent autoimmune diabetes in adults (LADA). A rapid deterioration of kidney function as well as poor diabetic control status at diagnosis was observed in all six cases. The ocular features of the patients showed acute progressive fibrovascular proliferation and relatively favorable postoperative visual acuity. PMID:24634886

  4. Multimodal Characterization of Proliferative Diabetic Retinopathy Reveals Alterations in Outer Retinal Function and Structure

    PubMed Central

    Boynton, Grace E.; Stem, Maxwell S.; Kwark, Leon; Jackson, Gregory R.; Farsiu, Sina; Gardner, Thomas W.

    2014-01-01

    diffusely thinned RPE layers (p=0.031) compared to controls. Conclusions Patients with untreated PDR exhibit inner retinal dysfunction, as evidenced by reduced contrast sensitivity and FDP performance, accompanied by alterations in inner and outer retinal structure. PRP-treated patients had more profound changes in outer retinal structure and function. Distinguishing the effects of PDR and PRP may guide the development of restorative vision therapies for patients with advanced diabetic retinopathy. PMID:25601533

  5. Association of reduced Connexin 43 expression with retinal vascular lesions in human diabetic retinopathy.

    PubMed

    Tien, Thomas; Muto, Tetsuya; Zhang, Joyce; Sohn, Elliott H; Mullins, Robert F; Roy, Sayon

    2016-05-01

    Connexin 43 (Cx43) downregulation promotes apoptosis in retinal vascular cells of diabetic animal models; however, its relevance to human diabetic retinopathy has not been established. In this study, we investigated whether diabetes alters Cx43 expression and promotes retinal vascular lesions in human retinas. Diabetic human eyes (aged 64-94 years) and non-diabetic human eyes (aged 61-90 years) were analyzed in this study. Retinal protein samples and retinal capillary networks were assessed for Cx43 level by Western blot (WB) analysis and immunostaining. In parallel, retinal capillary networks were stained with hematoxylin and periodic acid Schiff to determine the extent of pericyte loss (PL) and acellular capillaries (AC) in these retinas. Cx43 protein expression was significantly reduced in the diabetic retinas compared to non-diabetic retinas as indicated by WB analysis (81 ± 11% of control). Additionally, a significant decrease in the number of Cx43 plaques per unit length of vessel was observed in the diabetic retinas compared to those of non-diabetic retinas (62 ± 10% of control; p < 0.005). Importantly, a strong inverse relationship was noted between Cx43 expression and the relative number of AC (r = -0.89; p < 0.0005), and between Cx43 expression and number of pericyte loss (r = -0.88; p < 0.0005). Overall, these results show that Cx43 expression is reduced in the human diabetic retinas and Cx43 reduction is associated with increased vascular cell death. These findings suggest that diabetes decreases retinal Cx43 expression and that the development of PL and AC is associated with reduced Cx43 expression in human diabetic retinopathy. PMID:26738943

  6. Antagonism of CD11b with Neutrophil Inhibitory Factor (NIF) Inhibits Vascular Lesions in Diabetic Retinopathy

    PubMed Central

    Veenstra, Alexander A.; Tang, Jie; Kern, Timothy S.

    2013-01-01

    Leukocytes and proteins that govern leukocyte adhesion to endothelial cells play a causal role in retinal abnormalities characteristic of the early stages of diabetic retinopathy, including diabetes-induced degeneration of retinal capillaries. Leukocyte integrin αmβ2 (CD11b/CD18, MAC1), a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated leukocytes in vitro. We hypothesized that Neutrophil Inhibitory Factor (NIF), a selective antagonist of integrin αmβ2, would inhibit the diabetes-induced degeneration of retinal capillaries by inhibiting the excessive interaction between leukocytes and retinal endothelial cells in diabetes. Wild type animals and transgenic animals expressing NIF were made diabetic with streptozotocin and assessed for diabetes-induced retinal vascular abnormalities and leukocyte activation. To assess if the leukocyte blocking therapy compromised the immune system, animals were challenged with bacteria. Retinal superoxide production, leukostasis and leukocyte superoxide production were increased in wild type mice diabetic for 10 weeks, as was the ability of leukocytes isolated from diabetic animals to kill retinal endothelial cells in vitro. Retinal capillary degeneration was significantly increased in wild type mice diabetic 40 weeks. In contrast, mice expressing NIF did not develop any of these abnormalities, with the exception that non-diabetic and diabetic mice expressing NIF generated greater amounts of superoxide than did similar mice not expressing NIF. Importantly, NIF did not significantly impair the ability of mice to clear an opportunistic bacterial challenge, suggesting that NIF did not compromise immune surveillance. We conclude that antagonism of CD11b (integrin αmβ2) by NIF is sufficient to inhibit early stages of diabetic retinopathy, while not compromising the basic immune response. PMID:24205223

  7. Minocycline inhibits PARP-1 expression and decreases apoptosis in diabetic retinopathy

    PubMed Central

    WU, YING; CHEN, YONGDONG; WU, QIANG; JIA, LILI; DU, XINHUA

    2015-01-01

    The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy-associated cellular apoptosis. A total of 40 Sprague Dawley (SD) rats were used as a diabetic retinopathy model following injection with streptozotocin. Among the 34 rats in which the diabetes model was successfully established, 24 rats were divided into two experimental groups: I and II (T1 and T2, respectively), and orally administered with various doses of minocycline. The remaining 10 rats served as the diabetic retinopathy control group. An additional group of 10 healthy SD rats with comparable weight served as normal controls. The rats in T1 and T2 groups were treated daily for eight consecutive weeks with minocycline at a dose of 2.5 mg/kg and 5 mg/kg, respectively. The mRNA expression levels of poly (ADP-ribose) polymerase-1 (PARP-1) were subsequently measured by reverse transcription-quantitative polymerase chain reaction, and the protein expression levels of poly-ADP-ribose were measured by western blot analysis and immunohistochemistry. Retinal morphology was observed following hematoxylin and eosin staining, and retinal cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3 activity assays. The amplitudes of the electroretinogram (ERG) b-wave and oscillary potentials (OPs) were measured using visual electrophysiology, and compared among the four groups. The results of the present study demonstrated that in the diabetic rats, retinal PARP-1 gene expression was markedly upregulated, the number of apoptotic cells and the activity levels of caspase-3 were increased, and the amplitude of the ERG b-wave and the OPs were markedly lower as compared with the normal rats. Following treatment with minocycline, the abnormal expression of PARP-1 in the retina was inhibited, and cellular apoptosis was decreased. In conclusion, the results of the present study suggest that PARP-1 is involved in the

  8. Retinal Thickness in People with Diabetes and Minimal or No Diabetic Retinopathy: Heidelberg Spectralis Optical Coherence Tomography

    PubMed Central

    Chalam, Kakarla V.; Bressler, Susan B.; Edwards, Allison R.; Berger, Brian B.; Bressler, Neil M.; Glassman, Adam R.; Grover, Sandeep; Gupta, Shailesh K.; Nielsen, Jared S.

    2012-01-01

    Purpose. To evaluate macular thickness in people with diabetes but minimal or no retinopathy using Heidelberg Spectralis optical coherence tomography (OCT). Methods. In a multicenter, cross-sectional study of mean retinal thickness, on Spectralis OCT in the nine standard OCT subfields, spanning a zone with 6-mm diameter, center point, and total retinal volume were evaluated. Central subfield (CSF) thickness was evaluated for association with demographic and clinical factors. Stratus OCT scans also were performed on each participant. Results. The analysis included 122 eyes (122 participants) with diabetes and no (n = 103) or minimal diabetic retinopathy (n = 19) and no macular retinal thickening on clinical exam. Average CSF thickness was 270 ± 24 μm. Central subfield thickness was significantly greater in males relative to females (mean 278 ± 23 μm vs. 262 ± 22 μm, P < 0.001). After adjusting for gender, no additional factors were found to be significantly associated with CSF thickness (P > 0.10). Mean Stratus OCT CSF thickness was 199 ± 24 μm. Conclusions. Mean CSF thickness is approximately 70 μm thicker when measured with Heidelberg Spectralis OCT as compared with Stratus OCT among individuals with diabetes in the absence of retinopathy or with minimal nonproliferative retinopathy and a normal macular architecture. CSF thickness values ≥320 μm for males and 305 μm for females (∼2 SDs above the average for this normative cohort) are proposed as gender-specific thickness levels to have reasonable certainty that diabetic macular edema involving the CSF is present using Spectralis measurements. PMID:23132803

  9. Brightness-preserving fuzzy contrast enhancement scheme for the detection and classification of diabetic retinopathy disease.

    PubMed

    Datta, Niladri Sekhar; Dutta, Himadri Sekhar; Majumder, Koushik

    2016-01-01

    The contrast enhancement of retinal image plays a vital role for the detection of microaneurysms (MAs), which are an early sign of diabetic retinopathy disease. A retinal image contrast enhancement method has been presented to improve the MA detection technique. The success rate on low-contrast noisy retinal image analysis shows the importance of the proposed method. Overall, 587 retinal input images are tested for performance analysis. The average sensitivity and specificity are obtained as 95.94% and 99.21%, respectively. The area under curve is found as 0.932 for the receiver operating characteristics analysis. The classifications of diabetic retinopathy disease are also performed here. The experimental results show that the overall MA detection method performs better than the current state-of-the-art MA detection algorithms. PMID:26870750

  10. Influence of Age at Diagnosis and Time-Dependent Risk Factors on the Development of Diabetic Retinopathy in Patients with Type 1 Diabetes

    PubMed Central

    Forga, Luis; Goñi, María José; Cambra, Koldo; García-Mouriz, Marta; Iriarte, Ana

    2016-01-01

    Aim. To determine the influence of age at onset of type 1 diabetes and of traditional vascular risk factors on the development of diabetic retinopathy, in a cohort of patients who have been followed up after onset. Methods. Observational, retrospective study. The cohort consists of 989 patients who were followed up after diagnosis for a mean of 10.1 (SD: 6.8) years. The influence of age at diagnosis, glycemic control, duration of diabetes, sex, blood pressure, lipids, BMI, and smoking is analyzed using Cox univariate and multivariate models with fixed and time-dependent variables. Results. 135 patients (13.7%) developed diabetic retinopathy. The cumulative incidence was 0.7, 5.9, and 21.8% at 5-, 10-, and 15-year follow-up, respectively. Compared to the group with onset at age <10 years, the risk of retinopathy increased 2.5-, 3-, 3.3-, and 3.7-fold in the groups with onset at 10–14, 15–29, 30–44, and >44 years, respectively. During follow-up we also observed an association between diabetic retinopathy and HbA1c levels, HDL-cholesterol, and diastolic blood pressure. Conclusion. The rate of diabetic retinopathy is higher in patients who were older at type 1 diabetes diagnosis. In addition, we confirmed the influence of glycemic control, HDL-cholesterol, and diastolic blood pressure on the occurrence of retinopathy. PMID:27213158

  11. Imbalance of the Nerve Growth Factor and Its Precursor: Implication in Diabetic Retinopathy

    PubMed Central

    Mohamed, Riyaz; El-Remessy, Azza B

    2015-01-01

    Diabetic retinopathy is the leading cause of blindness in working age in US and worldwide. Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) are known to be essential for growth, differentiation and survival of neurons in the developing and mature retina. Nevertheless, a growing body of evidence supports an emerging role of neurotrophins in retinal diseases and in particular, diabetic retinopathy. Neurotrophins are initially synthesized in a pro-form and undergo proteolytic cleavage to produce the mature form that activates two distinctive receptors, the tyrosine kinase tropomycin receptor (Trk) and, to lesser extent, the common low affinity p75 neurotrophin receptor (p75NTR). Despite tight glycemic and metabolic control, many diabetic patients continue to experience progressive retinal damage. Understanding the molecular events involved in diabetic retinopathy is extremely important to identify novel therapeutic strategies to halt the disease progression. Diabetes induces imbalance in neurotrophins by increasing its proform, which is associated with upregulation of the p75NTR receptor in the retina. A growing body of evidence supports a link between the imbalance of pro-neurotrophins and early retinal inflammation, neuro-and microvascular degeneration. Therefore, examining changes in the levels of neurotrophins and its receptors might provide a therapeutically beneficial target to combat disease progression in diabetic patients. This commentary aims to highlight the impact of diabetes-impaired balance of neurotrophins and in particular, the NGF and its receptors; TrkA and p75NTR in the pathology of DR. PMID:26807305

  12. Prevalence, Awareness and Determinants of Diabetic Retinopathy in a Screening Centre in Nigeria.

    PubMed

    Kizor-Akaraiwe, Nkiru N; Ezegwui, Ifeoma R; Oguego, Ngozi; Uche, Nkechi J; N Asimadu, Ifeoma; Shiweobi, Jude

    2016-08-01

    There is a global rise in the prevalence of diabetes and this has led to a rise in the consequences of diabetes such as diabetic retinopathy (DR). The current study aims to determine the prevalence, awareness and determinants of DR among diabetics who attended a screening centre in Enugu, south-eastern Nigeria. A descriptive cross-sectional study was carried out among consenting diabetic patients who visited the centre. An interviewer-administered questionnaire was used to gather information on demographic details, the knowledge of the participants on effects of diabetes on the eye and previous care they had received for their eyes. Each participant underwent eye examination which included posterior segment examination with slit lamp biomicroscopy with +90DS lens after pupil dilation. A total of 80 eligible participants were examined. The prevalence of any DR among the participants was 32.1 % (95 % CI 20.6-43.5) whereas prevalence of proliferative diabetic retinopathy, PDR was 6.4 % and diabetic macular oedema, DME was 31.3 %. Age at onset of diabetes and duration of diabetes were the most determinant factors associated with DR (p = 0.039 and p = 0.000 respectively). Only ten (12.5 %) participants had undergone at least one specific eye examination to check for DR since they were diagnosed with diabetes. The major reason for not having had a prior screening is 'no one referred me for it' (31 participants, 44.3 %). DR is emerging as an important cause of blindness and severe visual impairment. Adequate screening programme and treatment protocol need to be set up for this population even in developing countries to prevent blindness. PMID:26810980

  13. Targeting carbonic anhydrase to treat diabetic retinopathy: Emerging evidences and encouraging results

    SciTech Connect

    Weiwei, Zhang; Hu, Renming

    2009-12-18

    Diabetic retinopathy (DR) is the leading cause of vision loss among working-age populations in developed countries. Current treatment options are limited to tight glycemic, blood pressure control and destructive laser surgery. Carbonic anhydrases (CAs) are a group of enzymes involving in the rapid conversion of carbon dioxide to bicarbonate and protons. Emerging evidences reveal CA inhibitors hold the promise for the treatment of DR. This article summarizes encouraging results from clinical and animal studies, and reviews the possible mechanisms.

  14. Association of bilirubin and malondialdehyde levels with retinopathy in type 2 diabetes mellitus

    PubMed Central

    Dave, Apoorva; Kalra, Pramila; Gowda, B. H. Rakshitha; Krishnaswamy, Malavika

    2015-01-01

    Introduction: Bilirubin as an antioxidant and malondialdehyde (MDA) as an oxidant have been shown to be associated with various complications of type 2 diabetes mellitus (DM). Aims and Objectives: The aim was to measure the levels of serum bilirubin and MDA in type 2 DM patients with and without diabetic retinopathy (DR) and to correlate them with severity of DR. Materials and Methods: A total number of 120 subjects out of which 40 were controls without type 2 DM and the rest 80 were type 2 DM patients were included in the study. Of those 80 diabetics, 44 patients did not have DR and 36 patients had DR. Results: The total bilirubin, direct bilirubin, indirect bilirubin were higher in controls as compared to cases (P = 0.017, 0.033, 0.024). Serum MDA levels were found to be higher in diabetics as compared to controls (P = 0.00). The values of all the three parameters, that is, total bilirubin, direct bilirubin and indirect bilirubin were lower in patients with retinopathy as compared to those without retinopathic changes (P = 0.00, 0.020, and 0.007). Subjects were assigned to quartiles based on serum total bilirubin concentration. The prevalence of DR was significantly lower among persons with the highest bilirubin quartile compared to those with the lowest quartile. The severity of DR was inversely proportional to the total bilirubin levels (P = 0.001). The multiple logistic regression analysis showed total bilirubin to be associated with prevalence of DR (P = 0.035). Conclusions: The levels of total bilirubin were significantly lower in patients with DR and also in the late stages of retinopathy as compared to those without retinopathy and in controls but MDA levels did not show any association with DR. PMID:25932393

  15. Strengthening diabetes retinopathy services in India: Qualitative insights into providers' perspectives: The India 11-city 9-state study

    PubMed Central

    Kannuri, Nanda Kishore; Anchala, Raghupathy; Murthy, Gudlavalleti V. S.; Gilbert, Clare E.

    2016-01-01

    Context: There is a lack of evidence on the subjective aspects of the provider perspective regarding diabetes and its complications in India. Objectives: The study was undertaken to understand the providers' perspective on the delivery of health services for diabetes and its complications, specifically the eye complications in India. Settings and Design: Hospitals providing diabetic services in government and private sectors were selected in 11 of the largest cities in India, based on geographical distribution and size. Methods: Fifty-nine semi-structured interviews conducted with physicians providing diabetes care were analyzed all interviews were recorded, transcribed, and translated. Nvivo 10 software was used to code the transcripts. Thematic analysis was conducted to analyze the data. Results: The results are presented as key themes: “Challenges in managing diabetes patients,” “Current patient management practices,” and “Strengthening diabetic retinopathy (DR) services at the health systems level.” Diabetes affects people early across the social classes. Self-management was identified as an important prerequisite in controlling diabetes and its complications. Awareness level of hospital staff on DR was low. Advances in medical technology have an important role in effective management of DR. A team approach is required to provide comprehensive diabetic care. Conclusions: Sight-threatening DR is an impending public health challenge that needs a concerted effort to tackle it. A streamlined, multi-dimensional approach where all the stakeholders cooperate is important to strengthening services dealing with DR in the existing health care setup. PMID:27144138

  16. Link between retinopathy and nephropathy caused by complications of diabetes mellitus type 2.

    PubMed

    Kotlarsky, Pavel; Bolotin, Arkady; Dorfman, Karina; Knyazer, Boris; Lifshitz, Tova; Levy, Jaime

    2015-02-01

    While the correlation and chronology of appearance of diabetic nephropathy and retinopathy is well known in diabetes mellitus (DM) type 1 patients, in DM type 2 this correlation is less clear. A retrospective study including 917 patients with type 2 diabetes. Diabetic retinopathy (DR) was diagnosed based on fundus photographs taken with a non-mydriatic camera. Diabetic nephropathy (DN) was diagnosed based on urinary albumin concentration in a morning urine sample. Statistical analysis was performed with a seemingly unrelated regression (SUR) model. Our SUR model is statistically significant: the test for "model versus saturated" is 2.20 and its significance level is 0.8205. The model revealed that creatinine and glomerular filtration rate (GFR) have strong influence on albuminuria, while body mass index (BMI) and HbA1c have less significant impact. DR is affected positively by diabetes duration, insulin treatment, glucose levels, and HbA1c, and it is affected negatively by GFR, triglyceride levels, and BMI. The association between DR and DN was statistically significant and had a unidirectional correlation, which can be explained by chronological order; that is, DN precedes DR. The present study indicates that the level of renal impairment is proportional to the level of damage to the eye. Furthermore, such an association has a chronological aspect; the renal injury precedes retinal damage. PMID:25391917

  17. An Innovative Australian Outreach Model of Diabetic Retinopathy Screening in Remote Communities

    PubMed Central

    Glasson, Nicola M.; Crossland, Lisa J.; Larkins, Sarah L.

    2016-01-01

    Background. Up to 98% of visual loss secondary to diabetic retinopathy (DR) can be prevented with early detection and treatment. Despite this, less than 50% of Australian and American diabetics receive appropriate screening. Diabetic patients living in rural and remote communities are further disadvantaged by limited access to ophthalmology services. Research Design and Methods. DR screening using a nonmydriatic fundal camera was performed as part of a multidisciplinary diabetes service already visiting remote communities. Images were onforwarded to a distant general practitioner who identified and graded retinopathy, with screen-positive patients referred to ophthalmology. This retrospective, descriptive study aims to compare the proportion of remote diabetic patients receiving appropriate DR screening prior to and following implementation of the service. Results. Of the 141 patients in 11 communities who underwent DR screening, 16.3% had received appropriate DR screening prior to the implementation of the service. In addition, 36.2% of patients had never been screened. Following the introduction of the service, 66.3% of patients underwent appropriate DR screening (p = 0.00025). Conclusion. This innovative model has greatly improved accessibility to DR screening in remote communities, thereby reducing preventable blindness. It provides a holistic, locally appropriate diabetes service and utilises existing infrastructure and health workforce more efficiently. PMID:26798648

  18. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy

    PubMed Central

    Jiang, Tingting; Cai, Jiyang; Fan, Jiawen; Zhang, Xiaozhe

    2016-01-01

    Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina. PMID:27143993

  19. Deletion of ocular transforming growth factor β signaling mimics essential characteristics of diabetic retinopathy.

    PubMed

    Braunger, Barbara M; Leimbeck, Sarah V; Schlecht, Anja; Volz, Cornelia; Jägle, Herbert; Tamm, Ernst R

    2015-06-01

    Diabetic retinopathy, a major cause of blindness, is characterized by a distinct phenotype. The molecular causes of the phenotype are not sufficiently clear. Here, we report that deletion of transforming growth factor β signaling in the retinal microenvironment of newborn mice induces changes that largely mimic the phenotype of nonproliferative and proliferative diabetic retinopathy in humans. Lack of transforming growth factor β signaling leads to the formation of abundant microaneurysms, leaky capillaries, and retinal hemorrhages. Retinal capillaries are not covered by differentiated pericytes, but by a coat of vascular smooth muscle-like cells and a thickened basal lamina. Reactive microglia is found in close association with retinal capillaries. In older animals, loss of endothelial cells and the formation of ghost vessels are observed, findings that correlate with the induction of angiogenic molecules and the accumulation of retinal hypoxia-inducible factor 1α, indicating hypoxia. Consequently, retinal and vitreal neovascularization occurs, a scenario that leads to retinal detachment, vitreal hemorrhages, neuronal apoptosis, and impairment of sensory function. We conclude that transforming growth factor β signaling is required for the differentiation of retinal pericytes during vascular development of the retina. Lack of differentiated pericytes initiates a scenario of structural and functional changes in the retina that mimics those of diabetic retinopathy strongly indicating a common mechanism. PMID:25857227

  20. [Update of diabetic retinopathy for Primary Care physicians: Towards an improvement of telematic medicine].

    PubMed

    Muñoz de Escalona-Rojas, J E; Quereda-Castañeda, A; García-García, O

    2016-04-01

    Diabetic retinopathy (DR) is considered the most common cause of blindness in the working-age population in industrialised countries, with diabetic macular oedema being the most common reason of decreased visual acuity in diabetics. According to the results of large multicentre studies, blindness prevention for RD involves conducting periodic check-ups, which include examinations of the back of the eye, so they can be treated in time. The use of non-mydriatic cameras and telemedicine have been shown to be useful in this regard (sensitivity>80% and specificity>90%). If this procedure is followed, the first retinography should be performed 5 years from diagnosis in type 1 diabetics and immediately after diagnosis in type 2 diabetics. Therefore the role of the Primary Care physician is crucial to enable early diagnosis of this disease. PMID:26239670

  1. Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes

    PubMed Central

    Pan, Jianbo; Liu, Sheng; Farkas, Michael; Consugar, Mark; Zack, Donald J.; Kozak, Igor; Arevalo, J. Fernando; Pierce, Eric; Qian, Jiang

    2016-01-01

    Purpose The risk of vision loss from proliferative diabetic retinopathy (PDR) can be reduced with timely detection and treatment. We aimed to identify serum molecular signatures that might help in the early detection of PDR in patients with diabetes. Methods A total of 40 patients with diabetes were recruited at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, 20 with extensive PDR and 20 with mild non-proliferative diabetic retinopathy (NPDR). The two groups were matched in age, gender, and known duration of diabetes. We examined the whole genome transcriptome of blood samples from the patients using RNA sequencing. We built a model using a support vector machine (SVM) approach to identify gene combinations that can classify the two groups. Results Differentially expressed genes were calculated from a total of 25,500 genes. Six genes (CCDC144NL, DYX1C1, KCNH3, LOC100506476, LOC285847, and ZNF80) were selected from the top 26 differentially expressed genes, and a combinatorial molecular signature was built based on the expression of the six genes. The mean area under receiver operating characteristic (ROC) curve was 0.978 in the cross validation. The corresponding sensitivity and specificity were 91.7% and 91.5%, respectively. Conclusions Our preliminary study defined a combinatorial molecular signature that may be useful as a potential biomarker for early detection of proliferative diabetic retinopathy in patients with diabetes. A larger-scale study with an independent cohort of samples is necessary to validate and expand these findings. PMID:27307695

  2. Regulation of Matrix Metalloproteinase-9 by Epigenetic Modifications and the Development of Diabetic Retinopathy

    PubMed Central

    Zhong, Qing; Kowluru, Renu A.

    2013-01-01

    Diabetes activates retinal matrix metalloproteinase-9 (MMP-9), and MMP-9 damages the mitochondria and augments capillary cell apoptosis. Our aim is to elucidate the mechanism responsible for MMP-9 activation. Histone modifications and recruitment of the nuclear transcriptional factor-κB (p65 subunit) at the MMP-9 promoter and the activity of lysine-specific demethylase 1 (LSD1) were measured in the retina from streptozotocin-induced diabetic rats. The role of LSD1 in MMP-9 activation was investigated in isolated retinal endothelial cells transfected with LSD1 small interfering RNA (siRNA). The results were confirmed in the retina from human donors with diabetic retinopathy. Diabetes decreased histone H3 dimethyl lysine 9 (H3K9me2) and increased acetyl H3K9 (Ac-H3K9) and p65 at the retinal MMP-9 promoter. LSD1 enzyme activity and its transcripts were elevated. LSD1 siRNA ameliorated the glucose-induced decrease in H3K9me2 and increase in p65 at the MMP-9 promoter, and prevented MMP-9 activation, mitochondrial damage, and cell apoptosis. Human donors with diabetic retinopathy had similar epigenetic changes at the MMP-9 promoter. Thus, activated LSD1 hypomethylates H3K9 at the MMP-9 promoter and this frees up that lysine 9 for acetylation. Increased Ac-H3K9 facilitates the recruitment of p65, resulting in MMP-9 activation and mitochondrial damage. Thus, the regulation of LSD1 by molecular or pharmacological means has the potential to retard the development of diabetic retinopathy. PMID:23423566

  3. Plasma Fibrinogen in Type 2 Diabetic Patients with Metabolic Syndrome and its Relation with Ischemic Heart Disease (IHD) and Retinopathy

    PubMed Central

    Mahendra, J.V.; Anuradha, T.S.; Talikoti, Prashanth; Nagaraj, R.S.; Vishali, V.

    2015-01-01

    Introduction: Metabolic syndrome or Syndrome X is characterized by hyperlipidemia, increased blood pressure, abdominal obesity and hyperglycemia, which increases the risk of cardiovascular complications. In addition to these, it is also associated with nontraditional risk factor like C- reactive protein, Plasminogen activator and fibrinogen. Various studies have documented association of these nontraditional risk factor, in Type 2 diabetes mellitus. Thus patients with diabetes mellitus are higher risk of developing micro and macro vascular complications like ischemic heart disease (IHD) and diabetic retinopathy. Diabetic retinopathy is the leading cause of decreased visual acuity, which is associated with maculopathy and profierative complications of it. Chronic hyperglycemia and its associated nonenzymatic glycation play an important role in the development of microangiopathy. Aims and Objectives: To study the prevalence of the metabolic syndrome in type 2 diabetes mellitus. To study the plasma fibrinogen and its relationship with IHD and retinopathy in type 2 Diabetes mellitus patients with metabolic syndrome. Materials and Methods: Patients of type 2 diabetes Mellitus were recruited based on the inclusion and exclusion criteria. History of IHD and ECG evidence of ischemia was obtained. Retinopathy was diagnosed by direct opthalmoscopy. Fasting glucose, lipid profile and plasma fibrinogen were analyzed. Stastical analysis was carried by Chi square test and student‘t’ test. Results: The prevalence of metabolic syndrome in study population of 100 type 2 diabetic patients is 58% and is significantly associated with duration of the disease (p<0.001). Fifty eight patients have hyperfibrinogenemia and mean fibrinogen level is significantly high in diabetic patients with metabolic syndrome when compared to diabetic patients without metabolic syndrome (p<0.001). Diabetic patient with metabolic syndrome and hyperfibrinogenemia have higher prevalence of IHD and

  4. [Active response to high momentum of diabetic retinopathy with the strategy of combined treatment and prevention].

    PubMed

    Xu, Xun; Zou, Haidong; Ning, Guang

    2015-11-01

    Diabetic retinopathy (DR) is an irreversible blinding eye disease. With the increased number of diabetes patients and aging population, China is now facing both the high prevalence rate and blindness rate of DR. It requires us to change the traditional mode and build a comprehensive, community-based system for DR prevention and treatment. The mainline is "Health Education-Screening-Referral-Treatment-Follow-up-Health Management". The public health resource and clinical resource should be effectively integrated into this system, so as to control high momentum of DR. PMID:26850579

  5. Intervention With an Erythropoietin-Derived Peptide Protects Against Neuroglial and Vascular Degeneration During Diabetic Retinopathy

    PubMed Central

    McVicar, Carmel M.; Hamilton, Ross; Colhoun, Liza M.; Gardiner, Tom A.; Brines, Michael; Cerami, Anthony; Stitt, Alan W.

    2011-01-01

    OBJECTIVE Erythropoietin (EPO) may be protective for early stage diabetic retinopathy, although there are concerns that it could exacerbate retinal angiogenesis and thrombosis. A peptide based on the EPO helix-B domain (helix B-surface peptide [pHBSP]) is nonerythrogenic but retains tissue-protective properties, and this study evaluates its therapeutic potential in diabetic retinopathy. RESEARCH DESIGN AND METHODS After 6 months of streptozotocin-induced diabetes, rats (n = 12) and age-matched nondiabetic controls (n = 12) were evenly split into pHBSP and scrambled peptide groups and injected daily (10 μg/kg per day) for 1 month. The retina was investigated for glial dysfunction, microglial activation, and neuronal DNA damage. The vasculature was dual stained with isolectin and collagen IV. Retinal cytokine expression was quantified using real-time RT-PCR. In parallel, oxygen-induced retinopathy (OIR) was used to evaluate the effects of pHBSP on retinal ischemia and neovascularization (1–30 μg/kg pHBSP or control peptide). RESULTS pHBSP or scrambled peptide treatment did not alter hematocrit. In the diabetic retina, Müller glial expression of glial fibrillary acidic protein was increased when compared with nondiabetic controls, but pHBSP significantly reduced this stress-related response (P < 0.001). CD11b+ microglia and proinflammatory cytokines were elevated in diabetic retina responses, and some of these responses were attenuated by pHBSP (P < 0.01–0.001). pHBSP significantly reduced diabetes-linked DNA damage as determined by 8-hydroxydeoxyguanosine and transferase-mediated dUTP nick-end labeling positivity and also prevented acellular capillary formation (P < 0.05). In OIR, pHBSP had no effect on preretinal neovascularization at any dose. CONCLUSIONS Treatment with an EPO-derived peptide after diabetes is fully established can significantly protect against neuroglial and vascular degenerative pathology without altering hematocrit or exacerbating

  6. Postprandial plasma fructose level is associated with retinopathy in patients with type 2 diabetes.

    PubMed

    Kawasaki, Takahiro; Ogata, Nobuyuki; Akanuma, Hiroshi; Sakai, Tadashi; Watanabe, Hiroyuki; Ichiyanagi, Kaoru; Yamanouchi, Toshikazu

    2004-05-01

    The aim of the present study was to investigate the association of fructose on microangiopathy in patients with diabetes. Postprandial plasma fructose concentrations and postprandial plasma glucose concentrations were simultaneously measured 3 times within a 24-hour period (2 hours after each meal) in 38 patients with type 2 diabetes that had been admitted to the hospital. The mean postprandial plasma fructose concentrations (MPPF) and the mean postprandial plasma glucose concentrations (MPPG) were calculated. Fructose was measured by gas chromatography-mass spectrometry (GCMS). Based solely on MPPF, we were able to divide the patients into three groups: the high MPPF (31.9 +/- 6.5 micromol/L) group (n = 12), the middle MPPF (21.2 +/- 1.8 micromol/L) group (n = 13), and the low MPPF (15.2 +/- 2.4 micromol/L) group (n = 13). Prevalence and degree of retinopathy and nephropathy were then evaluated in the 3 different groups. A significant correlation was observed in the prevalence of proliferative diabetic retinopathy (PDR) among the 3 MPPF groups (P =.024). The prevalence of PDR was higher in the high MPPF group (75.0%) than in the middle and low MPPF groups (23.1% and 38.5%, respectively). Although not significantly different statistically, the prevalence of all degrees of retinopathy showed a tendency to be higher in the high MPPF group (83.3%) than in the middle and low MPPF groups (46.2% and 46.2%, respectively) (P =.081). Nephropathy prevalence also showed a tendency to be higher in the high MPPF group (66.7%) than in the middle and low MPPF groups (38.5% and 30.8%, respectively), although the differences were not significant. The prevalence of clinical albuminuria was not significantly different among the 3 groups, but there was a tendency for it to be higher in the low MPPF group (30.8%) than in the high and middle MPPF groups (16.7% and 0%, respectively). No significant differences in glycemic indicators and mean duration of diabetes were observed among the 3

  7. MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy.

    PubMed

    Wang, Yang; Yan, Hua

    2016-01-01

    Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood-retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5/Occludin/ZO-1 genes expression, and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF/VEGFR, as well as VCAM-1/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF/VEGFR, VCAM-1/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects, and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects. PMID:27225425

  8. MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy

    PubMed Central

    Wang, Yang; Yan, Hua

    2016-01-01

    Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood–retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5/Occludin/ZO-1 genes expression, and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF/VEGFR, as well as VCAM-1/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF/VEGFR, VCAM-1/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects, and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects. PMID:27225425

  9. Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

    PubMed Central

    Jin, Jonghwa; Min, Hophil; Kim, Sang Jin; Oh, Sohee; Kim, Kyunggon; Yu, Hyeong Gon; Park, Taesung; Kim, Youngsoo

    2016-01-01

    Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR. PMID:26665153

  10. A study of red blood cell deformability in diabetic retinopathy using optical tweezers

    NASA Astrophysics Data System (ADS)

    Smart, Thomas J.; Richards, Christopher J.; Bhatnagar, Rhythm; Pavesio, Carlos; Agrawal, Rupesh; Jones, Philip H.

    2015-08-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) in which high blood sugar levels cause swelling, leaking and occlusions in the blood vessels of the retina, often resulting in a loss of sight. The microvascular system requires red blood cells (RBCs) to undergo significant cellular deformation in order to pass through vessels whose diameters are significantly smaller than their own. There is evidence to suggest that DM impairs the deformability of RBCs, and this loss of deformability has been associated with diabetic kidney disease (or nephropathy) - another microvascular complication of DM. However, it remains unclear whether reduced deformability of RBCs correlates with the presence of DR. Here we present an investigation into the deformability of RBCs in patients with diabetic retinopathy using optical tweezers. To extract a value for the deformability of RBCs we use a dual-trap optical tweezers set-up to stretch individual RBCs. RBCs are trapped directly (i.e. without micro-bead handles), so rotate to assume a `side-on' orientation. Video microscopy is used to record the deformation events, and shape analysis software is used to determine parameters such as initial and maximum RBC length, allowing us to calculate the deformability for each RBC. A small decrease in deformability of diabetes cells subject to this stretching protocol is observed when compared to control cells. We also report on initial results on three dimensional imaging of individual RBCs using defocussing microscopy.

  11. African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans

    PubMed Central

    Tandon, Arti; Chen, Ching J.; Penman, Alan; Hancock, Heather; James, Maurice; Husain, Deeba; Andreoli, Christopher; Li, Xiaohui; Kuo, Jane Z.; Idowu, Omolola; Riche, Daniel; Papavasilieou, Evangelia; Brauner, Stacey; Smith, Sataria O.; Hoadley, Suzanne; Richardson, Cole; Kieser, Troy; Vazquez, Vanessa; Chi, Cheryl; Fernandez, Marlene; Harden, Maegan; Cotch, Mary Frances; Siscovick, David; Taylor, Herman A.; Wilson, James G.; Reich, David; Wong, Tien Y.; Klein, Ronald; Klein, Barbara E. K.; Rotter, Jerome I.; Patterson, Nick; Sobrin, Lucia

    2015-01-01

    Purpose. To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). Methods. Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. Results. In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16–1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59–2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. Conclusions. In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present. PMID:26098467

  12. Stabilization of severe proliferative diabetic retinopathy by long-term treatment with SMS 201-995.

    PubMed

    Mallet, B; Vialettes, B; Haroche, S; Escoffier, P; Gastaut, P; Taubert, J P; Vague, P

    1992-01-01

    Growth hormone and growth factors have been implicated in the pathogenesis of diabetic retinopathy. Hypophysectomy has been proposed as a treatment for proliferative diabetic retinopathy unresolved by panretinal photocoagulation (PPC). SMS 201-995, a long acting somatostatin analogue which slows down growth hormone secretion, may provide a non-invasive therapy for these rare cases. To assess this possibility, we studied the feasibility and efficiency of long-term SMS 201-995 treatment in diabetics. SMS 201-995 was injected subcutaneously with a continuous pump system at a dose of 400 micrograms/d into 4 insulin dependent diabetic patients suffering from proliferative diabetic retinopathy progressing despite a pan-photocoagulation. The mean age of these patients was 29 +/- 3 years and mean disease duration 18 +/- 3 years. Treatment periods lasted from 6 to 20 months (mean 15 months). Mean 24-hour growth hormone levels decreased by 57% after only one month of treatment (7.4 +/- 1.9 mU/l to 3.2 +/- 0.9 mU/l). The decline continued up to the third month. After the sixth month, signs of resistance to the drug were noted. The frequency of 24-hour GH peaks over 10 mU/l followed a parallel pattern. No rebound was observed when the treatment was progressively discontinued. In 2 patients neovascularization stopped. In the other 2 the process regressed. In all treatment had beneficial effects on the retina. Overall visual acuity improved (7.8 +/- 0.8/10e vs 5.5 +/- 0.8/10e). These effects were obtained within 3 to 6 months. Glycosylated haemoglobin levels did not change (8.8 +/- 1.3% to 9.0 +/- 0.8%). Insulin doses decreased 41% (46.5 +/- 1.7 U/d to 27.3 +/- 3.0 U/d). No severe hypoglycaemia occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1297600

  13. C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

    PubMed Central

    Yang, Xiu-Fen; Deng, Yu; Gu, Hong; Lim, Apiradee; Snellingen, Torkel; Liu, Xi-Pu; Wang, Ning-Li; Domalpally, Amitha; Danis, Ronald; Liu, Ning-Pu

    2016-01-01

    AIM To investigate the relationship between C-reactive protein (CRP) and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS Community-based observational cohort study. There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing. Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire, ocular and anthropometric examinations and laboratory investigation. The presence and severity of DR were assessed by seven fields 30° color fundus photographs. Subjects were then classified into groups with no DR, any DR, or vision-threatening DR. CRP was analyzed from serum of study subjects. RESULTS A total of 1007 patients with T2DM were included for analysis, including 408 (40.5%) men and 599 (59.5%) women. The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men (P=0.004, OR 0.37, 95% CI 0.18-0.74). After adjusting for possible covariates, higher levels of CRP were associated with lower prevalence of any DR (P=0.02, OR 0.55, 95% CI 0.35-0.89), but not associated with vision-threatening DR (P=0.62, OR 0.78, 95% CI 0.28-2.14). After stratification by sex, the inverse association between CRP and DR was found to be statistically significant in men (P=0.006, OR 0.35, 95% CI 0.16-0.73), but not in women (P=0.58, OR 0.88, 95% CI 0.29-1.16). CONCLUSION The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR. PMID:26949620

  14. High Prevalence of Diabetic Retinopathy in Diabetic Patients Concomitant with Metabolic Syndrome

    PubMed Central

    Gao, Lu; Xin, Zhong; Yuan, Ming-Xia; Cao, Xi; Feng, Jian-Ping; Shi, Jing; Zhu, Xiao-Rong; Yang, Jin-Kui

    2016-01-01

    Objective To evaluate the relationship between metabolic syndrome (MetS) and the prevalence of diabetic retinopathy (DR). Research Design and Methods We conducted a case-controlled study, with data obtained from 2,551 Chinese participants between 18–79 years of age (representing a population of 1,660,500 in a district of Beijing). 74 cases of DR were found following data assessment by two 45° digital retinal images. Subjects without DR (NDR group) selected from the remaining 2,477 subjects were matched 1:1 to the DR group by HbA1c. MetS was defined by incorporating diagnostic criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). Results There were no statistical differences between the DR group and NDR group in a number of biological or laboratory tests. However, the percentage of patients with DR increased vs. patients without DR with the number of MetS components from 1 to 5 (14.3% vs. 85.7%, 38.9% vs. 61.1%, 49.1% vs. 50.9%, 61.4% vs. 38.6% and 83.3% vs. 16.7%, respectively) (Pearson χ2 = 9.938, P = 0.037). The trend to develop DR with MetS was significantly higher than that without MetS (NMetS) (χ2 = 5.540, P = 0.019). MetS was an independent statistical indicator of the presence of DR after adjusting for age and sex [odds ratio (95% CI): 2.701(1.248–5.849), P = 0.012], which is still the case with an additional adjustment for WC, SBP, TC, HbA1c and duration of diabetes [odds ratio (95% CI): 2.948(1.134–7.664), P = 0.027]. Conclusion DR is one of the diabetic microvascular complications. Apart from poor glycemic control, the concomitance of other metabolic factors can also influence DR. MetS, defined as a cluster of metabolic risk factors, is a strong and independent indicator of DR, even to the same extent as glycemic control. PMID:26745177

  15. Red Lesion Detection Using Dynamic Shape Features for Diabetic Retinopathy Screening.

    PubMed

    Seoud, Lama; Hurtut, Thomas; Chelbi, Jihed; Cheriet, Farida; Langlois, J M Pierre

    2016-04-01

    The development of an automatic telemedicine system for computer-aided screening and grading of diabetic retinopathy depends on reliable detection of retinal lesions in fundus images. In this paper, a novel method for automatic detection of both microaneurysms and hemorrhages in color fundus images is described and validated. The main contribution is a new set of shape features, called Dynamic Shape Features, that do not require precise segmentation of the regions to be classified. These features represent the evolution of the shape during image flooding and allow to discriminate between lesions and vessel segments. The method is validated per-lesion and per-image using six databases, four of which are publicly available. It proves to be robust with respect to variability in image resolution, quality and acquisition system. On the Retinopathy Online Challenge's database, the method achieves a FROC score of 0.420 which ranks it fourth. On the Messidor database, when detecting images with diabetic retinopathy, the proposed method achieves an area under the ROC curve of 0.899, comparable to the score of human experts, and it outperforms state-of-the-art approaches. PMID:26701180

  16. Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

    PubMed Central

    Wert, Katherine J; Mahajan, Vinit B; Zhang, Lijuan; Yan, Yuanqing; Li, Yao; Tosi, Joaquin; Hsu, Chun Wei; Nagasaki, Takayuki; Janisch, Kerstin M; Grant, Maria B; Mahajan, MaryAnn; Bassuk, Alexander G; Tsang, Stephen H

    2016-01-01

    Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders. PMID:27195131

  17. Potential Role of Cyr61 Induced Degeneration of Human Müller Cells in Diabetic Retinopathy

    PubMed Central

    Chen, Ding; Su, Zhitao; Jin, Ling; Wang, Lei; Hu, Zhixiang; Ke, Zhisheng; Song, Zongming

    2014-01-01

    The degeneration of Müller cells has been recognized to involve in the pathogenesis of diabetic retinopathy. However, the mechanism is not yet clear. This study is to explore the potential role of Cyr61, a secreted signaling protein in extracellular matrix, in inducing human Müller cell degeneration in diabetic retinopathy (DR). Twenty patients with proliferative diabetic retinopathy (PDR) and twelve non-diabetic patients were recruited for this study. Vitreous fluid was collected during vitrectomy surgery for Cyr61 ELISA. Human Müller cell line MIO-M1 were cultured to be subconfluent, and then treated with glucose (0–20 mM) or Cyr61 (0–300 ng/ml). Cyr61 expression induced by increasing concentrations of glucose was evaluated by RT-qPCR and Western blot. Effects of Cyr61 on Müller cells viability, migration and apoptosis were observed by MTT assay, Transwell assay, and TUNEL assay. Vitreous Cyr61 levels were observed to be 8-fold higher in patients with PDR (3576.92±1574.58 pg/mL), compared with non-diabetic controls (436.14±130.69 pg/mL). Interestingly, the active PDR group was significantly higher than the quiescent PDR group (P<0.01). In retinal Müller cells culture, high glucose significantly and dose-dependently elevated Cyr61 expression at both mRNA and protein levels. Cyr61 at high concentrations dose-dependently inhibited the viability and migration of Müller cells. TUNEL assay further revealed that high concentration of Cyr61 significantly promoted the cell apoptosis. In conclusion, these findings demonstrated for the first time that the expression of Cyr61 was elevated by high glucose in Müller cells, and Cyr61 inhibited cell viability and migration while induced apoptosis, suggesting the potential role of Cyr61 in Müller cell degeneration. The elevated Cyr61 levels in vitreous fluid of PDR patients further support its role in diabetic retinopathy (DR). PMID:25329584

  18. Current Trends in the Monitoring and Treatment of Diabetic Retinopathy in Young Adults

    PubMed Central

    Raczyńska, Dorota; Zorena, Katarzyna; Skorek, Andrzej; Malukiewicz, Grażyna; Sikorski, Bartosz L.

    2014-01-01

    The diagnosis and treatment of diabetic retinopathy (DR) in young adults have significantly improved in recent years. Research methods have widened significantly, for example, by introducing spectral optical tomography of the eye. Invasive diagnostics, for example, fluorescein angiography, are done less frequently. The early introduction of an insulin pump to improve the administration of insulin is likely to delay the development of diabetic retinopathy, which is particularly important for young patients with type 1 diabetes mellitus (T1DM). The first years of diabetes occurring during childhood and youth are the most appropriate to introduce proper therapeutic intervention before any irreversible changes in the eyes appear. The treatment of DR includes increased metabolic control, laserotherapy, pharmacological treatment (antiangiogenic and anti-inflammatory treatment, enzymatic vitreolysis, and intravitreal injections), and surgery. This paper summarizes the up-to-date developments in the diagnostics and treatment of DR. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual ophthalmology journals, books, and leading pharmaceutical company websites. PMID:24688225

  19. Current trends in the monitoring and treatment of diabetic retinopathy in young adults.

    PubMed

    Raczyńska, Dorota; Zorena, Katarzyna; Urban, Beata; Zalewski, Dominik; Skorek, Andrzej; Malukiewicz, Grażyna; Sikorski, Bartosz L

    2014-01-01

    The diagnosis and treatment of diabetic retinopathy (DR) in young adults have significantly improved in recent years. Research methods have widened significantly, for example, by introducing spectral optical tomography of the eye. Invasive diagnostics, for example, fluorescein angiography, are done less frequently. The early introduction of an insulin pump to improve the administration of insulin is likely to delay the development of diabetic retinopathy, which is particularly important for young patients with type 1 diabetes mellitus (T1DM). The first years of diabetes occurring during childhood and youth are the most appropriate to introduce proper therapeutic intervention before any irreversible changes in the eyes appear. The treatment of DR includes increased metabolic control, laserotherapy, pharmacological treatment (antiangiogenic and anti-inflammatory treatment, enzymatic vitreolysis, and intravitreal injections), and surgery. This paper summarizes the up-to-date developments in the diagnostics and treatment of DR. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual ophthalmology journals, books, and leading pharmaceutical company websites. PMID:24688225

  20. Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy

    PubMed Central

    Saleem, Saba; Azam, Aisha; Maqsood, Sundus Ijaz; Muslim, Irfan; Bashir, Shaheena; Fazal, Nosheen; Riaz, Moeen; Ali, Syeda Hafiza Benish; Niazi, Muhammad Khizar; Ishaq, Mazhar; Waheed, Nadia Khalida; Qamar, Raheel; Azam, Maleeha

    2015-01-01

    In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR). PMID:26658948

  1. Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy.

    PubMed

    Saleem, Saba; Azam, Aisha; Maqsood, Sundus Ijaz; Muslim, Irfan; Bashir, Shaheena; Fazal, Nosheen; Riaz, Moeen; Ali, Syeda Hafiza Benish; Niazi, Muhammad Khizar; Ishaq, Mazhar; Waheed, Nadia Khalida; Qamar, Raheel; Azam, Maleeha

    2015-01-01

    In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04-3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098-4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR). PMID:26658948

  2. Activation of Melanocortin Receptors MC1 and MC5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy

    PubMed Central

    Rossi, S.; Maisto, R.; Gesualdo, C.; Trotta, M. C.; Ferraraccio, F.; Kaneva, M. K.; Getting, S. J.; Surace, E.; Testa, F.; Simonelli, F.; Grieco, P.; Merlino, F.; Perretti, M.; D'Amico, M.; Di Filippo, C.

    2016-01-01

    We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12–16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 μL) of the selective MC1 small molecule agonist BMS-470539 (33 μmol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1β, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment. PMID:26949291

  3. Experimental study of the protective effects of SYVN1 against diabetic retinopathy

    PubMed Central

    Yang, Shuo; He, Heng; Ma, Qi Si; Zhang, Yong; Zhu, Ying; Wan, Xing; Wang, Feng Wen; Wang, Shuai Shuai; Liu, Lei; Li, Bin

    2015-01-01

    Genetic factors play an important role in the pathogenesis of diabetic retinopathy (DR). While many studies have focused on genes that increase susceptibility to DR, herein, we aimed to explore genes that confer DR resistance. Previously, we identified Hmg CoA reductase degradation protein 1 (SYVN1) as a putative DR protective gene via gene expression analysis. Transgenic mice overexpressing SYVN1 and wild-type (WT) mice with streptozotocin-induced diabetes were used in this experiment. Retinal damage and vascular leakage were investigated 6 months after induction of diabetes by histopathological and retinal cell apoptosis analyses and by retinal perfusion of fluorescein isothiocyanate-conjugated dextran. Compared with diabetic WT mice, diabetic SYVN1 mice had significantly more cells and reduced apoptosis in the retinal ganglion layer. Retinal vascular leakage was significantly lower in diabetic SYVN1 mice than in diabetic WT mice. The expression levels of endoplasmic reticulum (ER) stress-related, pro-inflammatory, and pro-angiogenic genes were also analyzed. Lower expression levels were observed in diabetic SYVN1 mice than in WT controls, suggesting that SYVN1 may play an important role in inhibiting ER stress, chronic inflammation, and vascular overgrowth associated with DR. Thus, these results strongly supported our hypothesis that SYVN1 confers DR resistance. PMID:26358086

  4. Dendrobium chrysotoxum Lindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

    PubMed Central

    Yu, Zengyang; Gong, Chenyuan; Lu, Bin; Yang, Li; Sheng, Yuchen; Ji, Lili; Wang, Zhengtao

    2015-01-01

    Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNFα), interleukin- (IL-) 6, and IL-1β in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ (IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1. PMID:25685822

  5. Automated fine structure image analysis method for discrimination of diabetic retinopathy stage using conjunctival microvasculature images

    PubMed Central

    Khansari, Maziyar M; O’Neill, William; Penn, Richard; Chau, Felix; Blair, Norman P; Shahidi, Mahnaz

    2016-01-01

    The conjunctiva is a densely vascularized mucus membrane covering the sclera of the eye with a unique advantage of accessibility for direct visualization and non-invasive imaging. The purpose of this study is to apply an automated quantitative method for discrimination of different stages of diabetic retinopathy (DR) using conjunctival microvasculature images. Fine structural analysis of conjunctival microvasculature images was performed by ordinary least square regression and Fisher linear discriminant analysis. Conjunctival images between groups of non-diabetic and diabetic subjects at different stages of DR were discriminated. The automated method’s discriminate rates were higher than those determined by human observers. The method allowed sensitive and rapid discrimination by assessment of conjunctival microvasculature images and can be potentially useful for DR screening and monitoring. PMID:27446692

  6. Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy.

    PubMed Central

    Williams, R; Nussey, S; Humphry, R; Thompson, G

    1986-01-01

    Non-mydriatic retinal photography with later interpretation of the photographs was assessed as a screening method for the detection of diabetic retinopathy; when compared with an ophthalmologist's clinical assessment in a random group of 62 diabetic patients it was accurate (false negative 6.8%, false positive 2%) and sensitive (sensitivity 96%, specificity 98%). The assessment of further management required based on analysis of the photographs was 96.5% in agreement with the further management suggested by the ophthalmologist after direct clinical assessment of the patient. If this technique were used to screen patients in a typical diabetic clinic the predicted positive accuracy rate would be 84% and the predicted negative accuracy rate 99.5%. Images p1141-a PMID:3094807

  7. Automated fine structure image analysis method for discrimination of diabetic retinopathy stage using conjunctival microvasculature images.

    PubMed

    Khansari, Maziyar M; O'Neill, William; Penn, Richard; Chau, Felix; Blair, Norman P; Shahidi, Mahnaz

    2016-07-01

    The conjunctiva is a densely vascularized mucus membrane covering the sclera of the eye with a unique advantage of accessibility for direct visualization and non-invasive imaging. The purpose of this study is to apply an automated quantitative method for discrimination of different stages of diabetic retinopathy (DR) using conjunctival microvasculature images. Fine structural analysis of conjunctival microvasculature images was performed by ordinary least square regression and Fisher linear discriminant analysis. Conjunctival images between groups of non-diabetic and diabetic subjects at different stages of DR were discriminated. The automated method's discriminate rates were higher than those determined by human observers. The method allowed sensitive and rapid discrimination by assessment of conjunctival microvasculature images and can be potentially useful for DR screening and monitoring. PMID:27446692

  8. Non-Traditional Systemic Treatments for Diabetic Retinopathy: An
Evidence-Based Review

    PubMed Central

    Simó, Rafael; Ballarini, Stefania; Cunha-Vaz, José; Ji, Linong; Haller, Hermann; Zimmet, Paul; Wong, Tien Y.

    2015-01-01

    The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR. PMID:25989912

  9. Angiographic evidence of peripheral ischemia in diabetic retinopathy and the risk of impending neovascularisation.

    PubMed

    Burton, David S M; Carrim, Zia I

    2015-02-01

    The appearance of biomicroscopic evidence of neovascularisation is the main indication for scatter laser treatment in patients with known diabetic eye disease. We describe a patient with an unusually aggressive variant of proliferative disease and a distinct angiographic signature. In an interventional case report with angiographic findings, we found that angiographic evidence of extensive capillary dropout in patients with known diabetic retinopathy should translate into a low threshold for panretinal photocoagulation treatment based on a high risk for progression to sight-threatening proliferative disease. Angiography may be a useful adjunct in stratifying patients with diabetic eye disease according to risk. Those with extensive ischemia, even without neovascularisation, should be considered for early panretinal photocoagulation. PMID:25282004

  10. Hypoxia and Dark Adaptation in Diabetic Retinopathy: Interactions, Consequences, and Therapy.

    PubMed

    Ramsey, David J; Arden, G B

    2015-12-01

    In diabetes, retinal blood flow is compromised, and retinal hypoxia is likely to be further intensified during periods of darkness. During dark adaptation, rod photoreceptors in the outer retina are maximally depolarized and continuously release large amounts of the neurotransmitter glutamate-an energetically demanding process that requires the highest oxygen consumption per unit volume of any tissue of the body. In complete darkness, even more oxygen is consumed by the outer retina, producing a steep fall in the retinal oxygen tension curve which reaches a nadir at the depth of the mitochondrial-rich rod inner segments. In contrast to the normal retina, the diabetic retina cannot meet the added metabolic load imposed by the dark-adapted rod photoreceptors; this exacerbates retinal hypoxia and stimulates the overproduction of vascular endothelial growth factor (VEGF). The use of nocturnal illumination to prevent dark adaptation, specifically reducing the rod photoreceptor dark current, should ameliorate diabetic retinopathy. PMID:26493191

  11. Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy.

    PubMed

    Behl, Tapan; Kotwani, Anita

    2015-09-01

    Diabetic retinopathy, a sight-threatening microvascular complication of diabetes mellitus, is initiated by retinal endothelial dysfunction and succeeded by various pathological events, eventually resulting in vision-loss. These events are regulated by numerous mediators, including vascular endothelial growth factor (VEGF), which induces the progression of various events characterizing diabetic retinopathy, such as neovascularization and macular edema. VEGF is physiologically required for regulating proliferation and assembling of endothelial cells, during vasculogenesis, as well as for their maintenance and survival throughout the lifetime of blood vessels. However, various pathological conditions are induced in the body during diabetes (such as ischemia, oxidative stress and overactivation of protein kinase C), which upregulate the expression of VEGF, thereby deviating it from its physiological role and leading to various pathological demonstrations such as angiogenesis, increased permeability of endothelium, decreased inhibition of pro-apoptotic proteins and activation of various other inflammatory mediators. Such events disrupt vascular homeostasis and play key roles in the pathophysiology of diabetic retinopathy. Hence, acknowledging various VEGF-mediated pathways helps in understanding the deeper aspects related to progression of this disorder. Targeting and inhibiting VEGF-mediated disease progression might provide an effective alternative therapy and hence prove beneficial in the treatment of diabetic retinopathy. PMID:26054568

  12. Medication adherence and quality of life among the elderly with diabetic retinopathy 1

    PubMed Central

    Jannuzzi, Fernanda Freire; Cintra, Fernanda Aparecida; Rodrigues, Roberta Cunha Matheus; São-João, Thaís Moreira; Gallani, Maria Cecília Bueno Jayme

    2014-01-01

    OBJECTIVE: to investigate the factors related to medication adherence and its relation to Health- Related Quality of Life (HRQoL) in elderly people with diabetic retinopathy. METHOD: one hundred (n=100) elderly outpatients with diabetic retinopathy taking antihypertensives and/or oral antidiabetics/insulin were interviewed. Adherence was evaluated by the adherence proportion and its association with the care taken in administrating medications and by the Morisky Scale. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was used to evaluate HRQoL. RESULTS: most (58%) reported the use of 80% or more of the prescribed dose and care in utilizing the medication. The item "stopping the drug when experiencing an adverse event", from the Morisky Scale, explained 12.8% and 13.5% of the variability of adherence proportion to antihypertensives and oral antidiabetics/insulin, respectively. CONCLUSION: there was better HRQoL in the Color Vision, Driving and Social Functioning domains of the NEI VFQ-25. Individuals with lower scores on the NEI VFQ-25 and higher scores on the Morisky Scale presented greater chance to be nonadherent to the pharmacological treatment of diabetes and hypertension. PMID:25591084

  13. A review of anti-VEGF agents for proliferative diabetic retinopathy

    PubMed Central

    Osaadon, P; Fagan, X J; Lifshitz, T; Levy, J

    2014-01-01

    Previous research has implicated vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic retinopathy (DR). Although many studies reviewed the use of anti-VEGF for diabetic macular oedema, little has been written about the use of anti-VEGF for proliferative diabetic retinopathy (PDR). This study is a review of relevant publications dealing with the use of anti-VEGF for the treatment of PDR. The articles were identified through systematic searches of PUBMED and the Cochrane Central Register of Controlled Trials. At the end of each section, we summarized the level of evidence of the scientific literature. Off-label use of anti-VEGF agents was found to be beneficial in PDR, especially in cases with neovascular glaucoma, persistent vitreous haemorrhage, and before vitrectomy. The disadvantages of the use of anti-VEGF are its short-effect duration, causing tractional retinal detachment in cases with pre-existing pre-retinal fibrosis and endophthalmitis in rare cases. There is no conclusive evidence from large randomized trials regarding the efficacy of anti-VEGF treatment in PDR. However, numerous case series, sound biochemical mechanism of action, and increasing experience with using anti-VEGF drugs can be used to support the ongoing use of this treatment modality in selected patients. PMID:24525867

  14. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

    PubMed Central

    Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

    2013-01-01

    AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

  15. GSTT1 Null Genotype Is a Risk Factor for Diabetic Retinopathy in Caucasians with Type 2 Diabetes, whereas GSTM1 Null Genotype Might Confer Protection against Retinopathy

    PubMed Central

    Cilenšek, Ines; Mankoč, Sara; Petrovič, Mojca Globočnik; Petrovič, Daniel

    2012-01-01

    Aim: Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy (DR). The aim of the present study was to investigate whether the genetic polymorphisms: polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 are associated with DR in Slovenian patients with type 2 diabetes. Methods: In this cross sectional case-control study 604 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 284 patients with DR (cases) and the control group of 320 subjects with type 2 diabetes of more than 10 years’ duration who had no clinical signs of DR. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: In our study, the deletion of the GSTM1 was found less frequent in cases with DR than in the controls (27.5% versus 44.4%; P < 0.001), whereas the deletion of GSTT1 was found significantly more often in cases than in the controls (49.3% versus 29.7%;P < 0.001). We did not find statistically significant differences in the genotype distribution in GSTP1 (Ile105Val) polymorphism between cases and controls (40.5% versus 46.0%). Conclusions: We may conclude that individuals homozygous for the deletion of GSTT1 are at an ≈ 2-fold-greater risk of DR, whereas the GSTM1 deficiency is associated with lower frequency of DR in type 2 diabetics. PMID:22377702

  16. Fortified Extract of Red Berry, Ginkgo biloba, and White Willow Bark in Experimental Early Diabetic Retinopathy

    PubMed Central

    Drago, Filippo

    2013-01-01

    Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control) rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS). Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats. PMID:23762874

  17. Association of potential salivary biomarkers with diabetic retinopathy and its severity in type-2 diabetes mellitus: a proteomic analysis by mass spectrometry

    PubMed Central

    Subrayan, Visvaraja

    2016-01-01

    Aim/hypothesis: The aim of our study was to characterize the human salivary proteome and determine the changes in protein expression in two different stages of diabetic retinopathy with type-2 diabetes mellitus: (1) with non-proliferative diabetic retinopathy (NPDR) and (2) with proliferative diabetic retinopathy (PDR). Type-2 diabetes mellitus without diabetic retinopathy (XDR) was designated as control. Method: In this study, 45 saliva samples were collected (15 samples from XDR control group, 15 samples from NPDR disease group and 15 samples from PDR disease group). Salivary proteins were extracted, reduced, alkylated, trypsin digested and labeled with an isobaric tag for relative and absolute quantitation (iTRAQ) before being analyzed by an Orbitrap fusion tribrid mass spectrometer. Protein annotation, fold change calculation and statistical analysis were interrogated by Proteome Discoverer. Biological pathway analysis was performed by Ingenuity Pathway Analysis. Data are available via ProteomeXchange with identifiers PXD003723–PX003725. Results: A total of 315 proteins were identified from the salivary proteome and 119 proteins were found to be differentially expressed. The differentially expressed proteins from the NPDR disease group and the PDR disease group were assigned to respective canonical pathways indicating increased Liver X receptor/Retinoid X receptor (LXR/RXR) activation, Farnesoid X receptor/Retinoid X receptor (FXR/RXR) activation, acute phase response signaling, sucrose degradation V and regulation of actin-based motility by Rho in the PDR disease group compared to the NPDR disease group. Conclusions/Interpretation: Progression from non-proliferative to proliferative retinopathy in type-2 diabetic patients is a complex multi-mechanism and systemic process. Furthermore, saliva was shown to be a feasible alternative sample source for diabetic retinopathy biomarkers. PMID:27280065

  18. Error analysis of filtering operations in pixel-duplicated images of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Mehrubeoglu, Mehrube; McLauchlan, Lifford

    2010-08-01

    In this paper, diabetic retinopathy is chosen for a sample target image to demonstrate the effectiveness of image enlargement through pixel duplication in identifying regions of interest. Pixel duplication is presented as a simpler alternative to data interpolation techniques for detecting small structures in the images. A comparative analysis is performed on different image processing schemes applied to both original and pixel-duplicated images. Structures of interest are detected and and classification parameters optimized for minimum false positive detection in the original and enlarged retinal pictures. The error analysis demonstrates the advantages as well as shortcomings of pixel duplication in image enhancement when spatial averaging operations (smoothing filters) are also applied.

  19. SOMA: A Proposed Framework for Trend Mining in Large UK Diabetic Retinopathy Temporal Databases

    NASA Astrophysics Data System (ADS)

    Somaraki, Vassiliki; Harding, Simon; Broadbent, Deborah; Coenen, Frans

    In this paper, we present SOMA, a new trend mining framework; and Aretaeus, the associated trend mining algorithm. The proposed framework is able to detect different kinds of trends within longitudinal datasets. The prototype trends are defined mathematically so that they can be mapped onto the temporal patterns. Trends are defined and generated in terms of the frequency of occurrence of pattern changes over time. To evaluate the proposed framework the process was applied to a large collection of medical records, forming part of the diabetic retinopathy screening programme at the Royal Liverpool University Hospital.

  20. Association of Complement C5 Gene Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Han Population

    PubMed Central

    Xu, Dengfeng; Yi, Hong; Yu, Shizhi; Li, Xiaosong; Qiao, Yanbin; Deng, Weiwei

    2016-01-01

    Purpose To investigate the association of C5 SNPs with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D). Methods A total of four C5 SNPs including rs2269067, rs7040033, rs1017119 and rs7027797 were genotyped in 400 PDR patients with T2D (cases) and 600 non- proliferative diabetic retinopathy PDR (NPDR) with T2D patients (controls) by using PCR-RFLP method. mRNA expression was examined by real-time PCR. Cytokine production was detected by ELISA. Results The frequency of GG genotype of C5 rs2269067 was significantly increased in cases compared with controls (Pc = 3.4×10−5, OR = 1.87). And C5 mRNA expression was significantly increased in rs2269067 GG cases as compared with CG or CC cases (P = 0.003, P = 0.001, respectively). Moreover, the production of IL-6 was significantly increased in rs2269067 GG cases compared to CG cases or CC cases (P = 0.002, P = 0.001, respectively). Conclusions C5 rs2269067 GG genotype confers risk for PDR of T2D in Chinese han population and is associated with an elevated C5 mRNA expression and an increased IL-6 production. PMID:26934706

  1. Association between Sickle Cell Trait and the Prevalence and Severity of Diabetic Retinopathy

    PubMed Central

    Al Harbi, Majed; Khandekar, Rajiv; Kozak, Igor

    2016-01-01

    Purpose To determine whether Sickle cell trait (SCT) is associated with an increased severity of diabetic retinopathy. Methods This was a single center retrospective study case control study of 100 eyes of 100 patients with diabetes mellitus (DM) with SCT (SCT group) and 100 eyes of 100 age-matched patients with DM without SCT (control group). The main outcome measure was the difference in the prevalence of sight threatening DR [here defined as diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR)], between the SCT and control groups. Secondary outcome measures included differences in visual acuity, ocular comorbidities, intraocular pressure, glycemic control as assessed by random blood glucose measurement, diabetes duration, nephropathy, hyperlipidemia and hypertension. Results The SCT group had statistically significantly shorter duration of DM (median [25% quartile] 15 [8.3] years versus 20 [14.7] years, respectively)(P<0.001) and presented with statistically better metabolic control (mean difference 1.6 mmol/l, (95% confidence interval [CI], 0.1–3.3;P = 0.03). The prevalence of PDR and/or DME was significantly lower in the SCT group (58%) compared to the control group, (95%)(P<0.001). The absence of SCT (adjusted odds ratio [AOR] = 24; 95% CI, 8–72; P<0.001) and longer duration of DM (AOR = 1.1 [95% CI, 1.02–1.13]; P = 0.003) were independent predictors of PDR and/or DME. Conclusions SCT seems to protect against the development and progression of DR. This may have implications for monitoring and screening. Prospective studies are required to confirm this association. If true, this association may indicate an increased blood glucose buffering capacity of abnormal hemoglobin. PMID:27414024

  2. The Association of Metabolic Syndrome with Diabetic Retinopathy: The Korean National Health and Nutrition Examination Survey 2008–2012

    PubMed Central

    Kim, Tai Kyong; Won, Jae Yon; Shin, Jeong Ah; Park, Yong-Moon; Yim, Hyeon Woo; Park, Young-Hoon

    2016-01-01

    Aims To explore gender differences and associations between metabolic syndrome (MetS) and its components, and diabetic retinopathy (DR) in Korean adults aged 40 years and older with diabetes. Methods We analyzed data from the Korean National Health and Nutrition Examination Surveys (2008–2012). In total, 2,576 type 2 diabetic participants, aged 40 and older, were evaluated. Seven standard retinal fundus photographs were obtained after pupil dilation in both eyes. DR was graded using the modified Airlie House classification system. Vision-threatening diabetic retinopathy (VTDR) included proliferative diabetic retinopathy and clinically significant macular edema. MetS was defined according to the Joint Interim Statement, proposed in 2009, by the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Multivariate logistic regression analysis was used to assess the relationship between MetS and its individual components with DR and VTDR. Results After controlling for confounders, MetS was not associated with DR in men or women. Moreover, the risk for DR or VTDR did not increase with increasing MetS components. However, high waist circumference was significantly inversely associated with VTDR (adjusted odds ratio = 0.36; 95% confidence interval = 0.14–0.93) only in men. Conclusions MetS was not associated with DR or VTDR in a Korean diabetic population. However, among MetS components, it seems that abdominal obesity was inversely associated with VTDR in Korean diabetic men. PMID:27275953

  3. Truncated netrin-1 contributes to pathological vascular permeability in diabetic retinopathy.

    PubMed

    Miloudi, Khalil; Binet, François; Wilson, Ariel; Cerani, Agustin; Oubaha, Malika; Menard, Catherine; Henriques, Sullivan; Mawambo, Gaelle; Dejda, Agnieszka; Nguyen, Phuong Trang; Rezende, Flavio A; Bourgault, Steve; Kennedy, Timothy E; Sapieha, Przemyslaw

    2016-08-01

    Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness in the working-age population. Impaired blood-retinal barrier function leads to macular edema that is closely associated with the deterioration of central vision. We previously demonstrated that the neuronal guidance cue netrin-1 activates a program of reparative angiogenesis in microglia within the ischemic retina. Here, we provide evidence in both vitreous humor of diabetic patients and in retina of a murine model of diabetes that netrin-1 is metabolized into a bioactive fragment corresponding to domains VI and V of the full-length molecule. In contrast to the protective effects of full-length netrin-1 on retinal microvasculature, the VI-V fragment promoted vascular permeability through the uncoordinated 5B (UNC5B) receptor. The collagenase matrix metalloprotease 9 (MMP-9), which is increased in patients with diabetic macular edema, was capable of cleaving netrin-1 into the VI-V fragment. Thus, MMP-9 may release netrin-1 fragments from the extracellular matrix and facilitate diffusion. Nonspecific inhibition of collagenases or selective inhibition of MMP-9 decreased pathological vascular permeability in a murine model of diabetic retinal edema. This study reveals that netrin-1 degradation products are capable of modulating vascular permeability, suggesting that these fragments are of potential therapeutic interest for the treatment of DR. PMID:27400127

  4. The Accuracy of Diagnostic Methods for Diabetic Retinopathy: A Systematic Review and Meta-Analysis

    PubMed Central

    Martínez-Vizcaíno, Vicente; Cavero-Redondo, Iván; Álvarez-Bueno, Celia; Rodríguez-Artalejo, Fernando

    2016-01-01

    Objective The objective of this study was to evaluate the accuracy of the recommended glycemic measures for diagnosing diabetic retinopathy. Methods We systematically searched MEDLINE, EMBASE, the Cochrane Library, and the Web of Science databases from inception to July 2015 for observational studies comparing the diagnostic accuracy of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour plasma glucose (2h-PG). Random effects models for the diagnostic odds ratio (dOR) value computed by Moses’ constant for a linear model and 95% CIs were used to calculate the accuracy of the test. Hierarchical summary receiver operating characteristic curves (HSROC) were used to summarize the overall test performance. Results Eleven published studies were included in the meta-analysis. The pooled dOR values for the diagnosis of retinopathy were 16.32 (95% CI 13.86–19.22) for HbA1c and 4.87 (95% CI 4.39–5.40) for FPG. The area under the HSROC was 0.837 (95% CI 0.781–0.892) for HbA1c and 0.735 (95% CI 0.657–0.813) for FPG. The 95% confidence region for the point that summarizes the overall test performance of the included studies occurs where the cut-offs ranged from 6.1% (43.2 mmol/mol) to 7.8% (61.7 mmol/mol) for HbA1c and from 7.8 to 9.3 mmol/L for FPG. In the four studies that provided information regarding 2h-PG, the pooled accuracy estimates for HbA1c were similar to those of 2h-PG; the overall performance for HbA1c was superior to that for FPG. Conclusions The three recommended tests for the diagnosis of type 2 diabetes in nonpregnant adults showed sufficient accuracy for their use in clinical settings, although the overall accuracy for the diagnosis of retinopathy was similar for HbA1c and 2h-PG, which were both more accurate than for FPG. Due to the variability and inconveniences of the glucose level-based methods, HbA1c appears to be the most appropriate method for the diagnosis diabetic retinopathy. PMID:27123641

  5. Knowledge, Attitude and Practice of Diabetic Retinopathy amongst the Diabetic Patients of AlJouf and Hail Province of Saudi Arabia

    PubMed Central

    2016-01-01

    Introduction Diabetes Mellitus (DM) is a metabolic disorder which is characterized by elevated blood sugar levels. It is a non-communicable disease and currently, a major disease of concern in terms of public health. Aim To assess the knowledge, attitude and practice of diabetic retinopathy amongst the diabetic patients of Saudi Arabia. Material and Methods Patients diagnosed with diabetes mellitus visiting to Ministry of Health hospitals were incorporated in this study. Self administered questionnaires were used to assess knowledge, attitude and practice of diabetic retinopathy amongst the diabetic patients. The data collected was entered in a pre-designed proforma and analysed using SPSS version 20.0 Results This study incorporated 439 diabetic individuals out of which 251 (57.17%) were male patients and 188 (42.82%) were females. Majority of the diabetic patients (75.62%) were aware that diabetes can cause eye disorders, 73.80% of patients replied that diabetic individuals should go for regular eye check-ups and 65.10% of patients were aware that they should visit an ophthalmologist in the event of eye problem. Out of 439 diabetic 302 patients (68.79%) were aware that timely treatment can prevent or delay damage of eyes in diabetic patients and about 95% of all the participants went for regular ocular examinations. Conclusion Majority of the diabetes patients were aware that diabetes can cause eye disease and it is necessary for the diabetic individuals to consult the ophthalmologist for the prevention of the same. PMID:27437254

  6. Assessment of Automated Disease Detection in Diabetic Retinopathy Screening Using Two-Field Photography

    PubMed Central

    Goatman, Keith; Charnley, Amanda; Webster, Laura; Nussey, Stephen

    2011-01-01

    Aim To assess the performance of automated disease detection in diabetic retinopathy screening using two field mydriatic photography. Methods Images from 8,271 sequential patient screening episodes from a South London diabetic retinopathy screening service were processed by the Medalytix iGrading™ automated grading system. For each screening episode macular-centred and disc-centred images of both eyes were acquired and independently graded according to the English national grading scheme. Where discrepancies were found between the automated result and original manual grade, internal and external arbitration was used to determine the final study grades. Two versions of the software were used: one that detected microaneurysms alone, and one that detected blot haemorrhages and exudates in addition to microaneurysms. Results for each version were calculated once using both fields and once using the macula-centred field alone. Results Of the 8,271 episodes, 346 (4.2%) were considered unassessable. Referable disease was detected in 587 episodes (7.1%). The sensitivity of the automated system for detecting unassessable images ranged from 97.4% to 99.1% depending on configuration. The sensitivity of the automated system for referable episodes ranged from 98.3% to 99.3%. All the episodes that included proliferative or pre-proliferative retinopathy were detected by the automated system regardless of configuration (192/192, 95% confidence interval 98.0% to 100%). If implemented as the first step in grading, the automated system would have reduced the manual grading effort by between 2,183 and 3,147 patient episodes (26.4% to 38.1%). Conclusion Automated grading can safely reduce the workload of manual grading using two field, mydriatic photography in a routine screening service. PMID:22174741

  7. Exudate detection in color retinal images for mass screening of diabetic retinopathy.

    PubMed

    Zhang, Xiwei; Thibault, Guillaume; Decencière, Etienne; Marcotegui, Beatriz; Laÿ, Bruno; Danno, Ronan; Cazuguel, Guy; Quellec, Gwénolé; Lamard, Mathieu; Massin, Pascale; Chabouis, Agnès; Victor, Zeynep; Erginay, Ali

    2014-10-01

    The automatic detection of exudates in color eye fundus images is an important task in applications such as diabetic retinopathy screening. The presented work has been undertaken in the framework of the TeleOphta project, whose main objective is to automatically detect normal exams in a tele-ophthalmology network, thus reducing the burden on the readers. A new clinical database, e-ophtha EX, containing precisely manually contoured exudates, is introduced. As opposed to previously available databases, e-ophtha EX is very heterogeneous. It contains images gathered within the OPHDIAT telemedicine network for diabetic retinopathy screening. Image definition, quality, as well as patients condition or the retinograph used for the acquisition, for example, are subject to important changes between different examinations. The proposed exudate detection method has been designed for this complex situation. We propose new preprocessing methods, which perform not only normalization and denoising tasks, but also detect reflections and artifacts in the image. A new candidates segmentation method, based on mathematical morphology, is proposed. These candidates are characterized using classical features, but also novel contextual features. Finally, a random forest algorithm is used to detect the exudates among the candidates. The method has been validated on the e-ophtha EX database, obtaining an AUC of 0.95. It has been also validated on other databases, obtaining an AUC between 0.93 and 0.95, outperforming state-of-the-art methods. PMID:24972380

  8. Relationship between Altered Platelet Morphological Parameters and Retinopathy in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Yilmaz, Tolga; Yilmaz, Ahu

    2016-01-01

    Purpose. To investigate whether platelet morphology or function is altered in patients with diabetic retinopathy (DR). Methods. This prospective study enrolled 85 healthy controls (HCs) (group 1) and 262 patients with Type 2 diabetes mellitus (T2DM). Patients were subclassified into three groups according to ocular findings: no DR (group 2; n = 88); nonproliferative DR (group 3; n = 88), and proliferative DR (group 4; n = 86). Mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), plateletcrit (PCT) values, and platelet count were measured in the studied groups. Results. MPV, PDW, and PLCR levels were significantly altered in groups 2–4 compared with HCs (p < 0.05, p < 0.05, p < 0.05). Compared with group 2, both DR groups had higher MPV and PDW levels, with a significant difference between groups 2 and 4 for both MPV (p = 0.036) and PDW (p = 0.006). PLCR correlated with retinopathy stage, but no significant difference was found between the DR groups. Platelet count and PCT values were not significantly different between the groups (p > 0.05). Conclusion. Our findings suggest an association between mean platelet indices (MPI) (i.e., MPV, PDW, and PLCR) and DR stage. Therefore, MPI could be a beneficial prognostic marker of DR in patients with T2DM. PMID:27190641

  9. A decision support system for automatic screening of non-proliferative diabetic retinopathy.

    PubMed

    Reza, Ahmed Wasif; Eswaran, C

    2011-02-01

    The increasing number of diabetic retinopathy (DR) cases world wide demands the development of an automated decision support system for quick and cost-effective screening of DR. We present an automatic screening system for detecting the early stage of DR, which is known as non-proliferative diabetic retinopathy (NPDR). The proposed system involves processing of fundus images for extraction of abnormal signs, such as hard exudates, cotton wool spots, and large plaque of hard exudates. A rule based classifier is used for classifying the DR into two classes, namely, normal and abnormal. The abnormal NPDR is further classified into three levels, namely, mild, moderate, and severe. To evaluate the performance of the proposed decision support framework, the algorithms have been tested on the images of STARE database. The results obtained from this study show that the proposed system can detect the bright lesions with an average accuracy of about 97%. The study further shows promising results in classifying the bright lesions correctly according to NPDR severity levels. PMID:20703589

  10. Potential therapeutic effects of pigment epithelium-derived factor for treatment of diabetic retinopathy.

    PubMed

    Liu, Xiao; Chen, Hui-Hui; Zhang, Li-Wei

    2013-01-01

    Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR. PMID:23638428

  11. Systematic review of various laser intervention strategies for proliferative diabetic retinopathy.

    PubMed

    Luo, Dawei; Zheng, Zhi; Xu, Xun; Fan, Ying; Zhu, Bijun; Liu, Kun; Wang, Fenghua; Sun, Xiaodong; Zou, Haidong; Xia, Xin

    2015-01-01

    Diabetic retinopathy (DR) is a common complication of diabetes. DR obstructs blood supply to the retina and has serious and long-lasting detrimental effects on quality of life. Panretinal photocoagulation, a laser surgical intervention, is advocated for early treatment of DR to prevent visual loss; however, results from studies reporting its efficacy vary markedly. In this review, we systematically conducted a database search of randomized controlled trials that investigated the safety and efficacy of different types of laser interventions, alone or in combination with adjunct intravitreal steroid utilization, in patients with DR. Data from 14 studies demonstrated that panretinal photocoagulation can be a safe and effective option for reducing visual loss and blindness in patients with DR. PMID:25154790

  12. Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

    PubMed Central

    Varano, Monica; Mallozzi, Cinzia; Gaddini, Lucia; Formisano, Giuseppe; Pricci, Flavia

    2015-01-01

    Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight. PMID:25688355

  13. Situational analysis of services for diabetes and diabetic retinopathy and evaluation of programs for the detection and treatment of diabetic retinopathy in India: Methods for the India 11-city 9-state study

    PubMed Central

    Murthy, G. V. S.; Gilbert, Clare E.; Shukla, Rajan; Vashist, Praveen; Shamanna, B. R.

    2016-01-01

    Background: Diabetic retinopathy (DR) is a leading cause of visual impairment in India. Available evidence shows that there are more than 60 million persons with diabetes in India and that the number will increase to more than a 100 million by 2030. There is a paucity of data on the perceptions and practices of persons with diabetes and the available infrastructure and uptake of services for DR in India. Objectives: Assess perception of care and challenges faced in availing eye care services among persons with diabetics and generate evidence on available human resources, infrastructure, and service utilization for DR in India. Methods: The cross-sectional, hospital-based survey was conducted in eleven cities across 9 States in India. In each city, public and private providers of eye-care were identified. Both multispecialty and standalone facilities were included. Specially designed semi-open ended questionnaires were administered to the clients. Semi-structured interviews were administered to the service providers (both diabetic care physicians and eye care teams) and observational checklists were used to record findings of the assessment of facilities conducted by a dedicated team of research staff. Results: A total of 859 units were included in this study. This included 86 eye care and 73 diabetic care facilities, 376 persons with diabetes interviewed in the eye clinics and 288 persons with diabetes interviewed in the diabetic care facilities. Conclusions: The findings will have significant implications for the organization of services for persons with diabetes in India. PMID:27144132

  14. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy

    PubMed Central

    Navitskaya, Svetlana; O’Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B.; Busik, Julia V.

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy. PMID:26760976

  15. Extending the diabetic retinopathy screening interval beyond 1 year: systematic review.

    PubMed

    Taylor-Phillips, Sian; Mistry, Hema; Leslie, Rachael; Todkill, Dan; Tsertsvadze, Alexander; Connock, Martin; Clarke, Aileen

    2016-01-01

    To determine whether the recommended screening interval for diabetic retinopathy (DR) in the UK can safely be extended beyond 1 year. Systematic review of clinical and cost-effectiveness studies. Nine databases were searched with no date restrictions. Randomised controlled trials (RCTs), cohort studies, prognostic or economic modelling studies which described the incidence and progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes mellitus of either sex and of any age reporting incidence and progression of DR in relation to screening interval (vs annual screening interval) and/or prognostic factors were included. Narrative synthesis was undertaken. 14,013 papers were identified, of which 11 observational studies, 5 risk stratification modelling studies and 9 economic studies were included. Data were available for 262,541 patients of whom at least 228,649 (87%) had type 2 diabetes. There were no RCTs. Studies concluded that there is little difference between clinical outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there was high loss to follow-up (13-31%), heterogeneity in definitions of low risk and variation in screening and grading protocols for prior retinopathy results. Observational and economic modelling studies in low-risk patients show little difference in clinical outcomes between 1-year and 2-year screening intervals. The lack of experimental research designs and heterogeneity in definition of low risk considerably limits the reliability and validity of this conclusion. Cost-effectiveness findings were mixed. There is insufficient evidence to recommend a move to extend the screening interval beyond 1 year. PMID:25586713

  16. Extending the diabetic retinopathy screening interval beyond 1 year: systematic review

    PubMed Central

    Taylor-Phillips, Sian; Mistry, Hema; Leslie, Rachael; Todkill, Dan; Tsertsvadze, Alexander; Connock, Martin; Clarke, Aileen

    2016-01-01

    To determine whether the recommended screening interval for diabetic retinopathy (DR) in the UK can safely be extended beyond 1 year. Systematic review of clinical and cost-effectiveness studies. Nine databases were searched with no date restrictions. Randomised controlled trials (RCTs), cohort studies, prognostic or economic modelling studies which described the incidence and progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes mellitus of either sex and of any age reporting incidence and progression of DR in relation to screening interval (vs annual screening interval) and/or prognostic factors were included. Narrative synthesis was undertaken. 14 013 papers were identified, of which 11 observational studies, 5 risk stratification modelling studies and 9 economic studies were included. Data were available for 262 541 patients of whom at least 228 649 (87%) had type 2 diabetes. There were no RCTs. Studies concluded that there is little difference between clinical outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there was high loss to follow-up (13–31%), heterogeneity in definitions of low risk and variation in screening and grading protocols for prior retinopathy results. Observational and economic modelling studies in low-risk patients show little difference in clinical outcomes between 1-year and 2-year screening intervals. The lack of experimental research designs and heterogeneity in definition of low risk considerably limits the reliability and validity of this conclusion. Cost-effectiveness findings were mixed. There is insufficient evidence to recommend a move to extend the screening interval beyond 1 year. PMID:25586713

  17. Screening and Public Health Strategies for Diabetic Retinopathy in the Eastern Mediterranean Region

    PubMed Central

    Khandekar, Rajiv

    2012-01-01

    Diabetic retinopathy (DR) is a complication of diabetes mellitus that can cause blindness. As the prevalence of diabetes increases globally and patients live longer, the cases of DR are increasing. To address the visual disabilities due to DR, screening of all diabetics is suggested for early detection. The rationale and principles of DR screening are discussed. Based on the available evidence, the magnitude of DR in countries in the Eastern Mediterranean region (EMR) is presented. Public health strategies to control visual disabilities due to DR are discussed. These include generating evidence for planning, implementing standard operating procedures, periodic DR screening, focusing on primary prevention of DR, strengthening DR management, health information management and retrieval systems for DR, rehabilitating DR visually disabled, using low-cost technologies, adopting a comprehensive approach by integrating DR care into the existing health systems, health promotion/counseling, and involving the community. Although adopting the public health approach for DR has been accepted as a priority by member countries of EMR, challenges in implementation remain. These include limitations in the public health approach for DR compared to that for cataract, few skilled workers, poor health systems and lack of motivation in affecting health-related lifestyle changes in diabetics.Visual disabilities due to DR are likely to increase in the coming years. An organized public health approach must be adopted and all stakeholders must work together to control severe visual disabilities due to DR. PMID:22623855

  18. An assessment of knowledge, attitude and practices (KAP) towards diabetes and diabetic retinopathy in a suburban town of Karachi

    PubMed Central

    Memon, Muhammad Saleh; Shaikh, Sikander Ali; Shaikh, Abdul Rashid; Fahim, Muhammad Faisal; N. Mumtaz, Seema; Ahmed, Nadeem

    2015-01-01

    Objective: To assess the Knowledge, Attitude and Practices (KAP) towards diabetes and diabetic retinopathy in the general population of Bin Qasim Town (BQ), Karachi. Methods: An observational, cross-sectional study was approved by Research Ethical Committee of Al-Ibrahim Eye Hospital. It included every third household by stratified sampling in each Union Council of (BQ) Town, in the months of May to July 2013. The interview Questionnaire included 43 questions, of qualitative and quantitative aspects, which were awarded 56 scoring points. SPSS version 20.0 was used to analyze the data. Results: Six hundred ninety two adults one from each household were interviewed. Of the total respondents, 271 (39.2%) had diabetes. Lowest mean knowledge score (5.28 ± 6.09) was seen in illiterate respondents. Male’s Mean Knowledge score (7.61 ± 6.600) was better than female’s (5.46 ± 6.21) with P <0.001. Over all mean score of Attitudes towards diabetes was 5.43 ± 2.57. It was higher (6.62 ± 2.03) in diabetic respondents as compared with non-diabetic respondents (4.70 ± 2.59) with p < 0.000. In Practice module majority of the respondents (69.9%) did not exercise, 49% took high caloric snacks between meals and 87% ate outside home once a month, 56.8% diabetics visited ophthalmologist for routine eye examination; but only 9.2% asked for retinal examination. Conclusion: Lack of knowledge of diabetes was found in the surveyed community, more marked in females, illiterate and the individuals not having diabetes. PMID:25878640

  19. Krogh cylinders in retinal development, panretinal hypoperfusion and diabetic retinopathy.

    PubMed

    McLeod, David

    2010-12-01

    The volume of cells that a length of capillary supplies with O(2) is called a Krogh cylinder. This geometric 'tissue unit' was named after the Danish zoophysiologist and Nobel laureate August Krogh who made important discoveries in the fields of external and internal respiration in the first half of the last century. Krogh's ideas concerning tissue O(2) distribution can be extrapolated to retinal oxygenation by larger vessels (including arterioles, arteries and even veins) and by vessel groups within higher-order 'microvascular units' (including the choroid). During retinal development, for example, the difference in pO(2) levels within arteries and capillaries determines Krogh cylinders of different radius and establishes the periarterial capillary-free zone of His. The O(2) supply to the venous end of a tissue unit may be compromised during periods of reduced perfusion, increased O(2) consumption or hypoxaemia, resulting in an 'anoxic corner' of the Krogh cylinder. A funnel of hypometabolic (and therefore hypoxia-tolerant) cells will likely intervene between the necrotic cells and unaffected cells located closer to the O(2) source. Macular perivenular whitening heralds anoxic corners and/or hypoxic funnels owing to hypoperfusion within second-order microvascular units. In eyes with extensive retinal capillary closure from diabetes, Krogh cylinders surround the medium-sized arteries and veins that form arteriovenous shunts while traversing the midperipheral retina. These isolated tissue units incorporate an outer sheath of hypoxic cells within which vascular endothelial growth factor is upregulated. This 'angiogenic sheath' expands following retinal detachment; it corresponds to the hypoxia-tolerant funnel within capillary-based tissue units and to the cerebral penumbra after stroke. PMID:20064121

  20. United Kingdom National Ophthalmology Database Study: Diabetic Retinopathy; Report 1: prevalence of centre-involving diabetic macular oedema and other grades of maculopathy and retinopathy in hospital eye services

    PubMed Central

    Keenan, T D L; Johnston, R L; Donachie, P H J; Sparrow, J M; Stratton, I M; Scanlon, P

    2013-01-01

    Aims To report estimates of the prevalence of diabetic retinopathy (DR) and maculopathy grades for a large cohort of patients managed by the UK hospital eye service (HES). Methods Anonymised data were extracted from 30 UK NHS hospital trusts using a single ophthalmic electronic medical record (EMR) for the period from April 2000 to November 2010 to create the National Ophthalmology Database (NOD). From 2007, the EMR facilitated capture of a nationally agreed-upon standardised data set (DR Structured Assessment) relating to the presence or absence of clinical signs of DR and maculopathy. An algorithm in the software automatically calculated the Early Treatment of Diabetic Retinopathy Study grades of retinopathy and maculopathy. Results Between 2007 and 2010, 307 538 patients had data on the NOD, with 76 127 (24.8%) patients having been recorded as having diabetes. The proportion of patients with diabetes who had a structured assessment increased from 50.7% (2007) to 86.8% (2010). In each NHS year, 12.6–20.6% of eyes with structured assessments had no DR; 59.6–67.3% had non-proliferative DR; and 18.3–20.9% had active or regressed proliferative DR. Clinically significant macular oedema was present in 15.8–18.1% of eyes, and in 8.7–10.0% of eyes, this involved the central macula. Conclusion This study provides contemporary estimates of the prevalence of retinopathy and maculopathy grades in a large cohort of patients with diabetes managed by the UK HES. Centre-involving diabetic macular oedema, potentially amenable to anti-VEGF therapy, is present in the eyes of almost 10% of these patients. This information is useful for clinicians, health-care economists, and commissioners involved in planning and delivering diabetic eye services. PMID:24051410

  1. Effect ofOcimum sanctum (Tulsi) and vitamin E on biochemical parameters and retinopathy in streptozotocin induced diabetic rats.

    PubMed

    Halim, Eshrat M; Mukhopadhyay, A K

    2006-09-01

    This study was carried out to see the effect of the aqueous extract ofOcitum sanctum Linn (Tulsi) with Vitamin E on biochemical parameters and retinopathy in the streptozotocin-induced diabetic albino male rats. Adult albino male rats weighing 150-200 gm were made diabetic by intraperitoneal injection of streptozotocin in the dose 60 mg/kg in citrate buffer (pH 6.3). The diabetic animals were left for one month to develop retinopathy. Biochemical parameters like plasma glucose, oral glucose tolerance and glycosylated hemoglobin HbA(1c), were measured along with lipid profile, and enzymes like glutathione peroxidase (GPX), lipid peroxidase (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in normal, untreated diabetic rats and diabetic rats treated withOcimum sanctum L extracts and vitamin E. Fluorescein angiography test was done for assessing retinopathy. Results on biochemical parameters were analyzed statistically by using ANOVA followed by Dunnet's 't'-test. A p-value of <0.05 was considered as significant. Evaluation of biochemical profile in treated groups showed statistically significant reduction in plasma levels of glucose, HbA(1c), lipid profile and LPO, and elevation of GPX, SOD, CAT and GST. Treatment of the diabetic animals withOcimum sanctum and Vitamin E, alone and in combination for 16 weeks showed reversal of most of the parameters studied including plasma glucose levels. Angiography showed improvement in retinal changes following combined antidiabetic treatment. PMID:23105641

  2. Short-term intraocular pressure changes after intravitreal injection of bevacizumab in diabetic retinopathy patients

    PubMed Central

    Farhood, Qasim Kadhim; Twfeeq, Sinan Mohammad

    2014-01-01

    Background This study examined the changes in short-term intraocular pressure (IOP) in a prospective series of patients undergoing intravitreal bevacizumab injection. The aim was to evaluate the frequency and predictive factors related to intraocular pressure (IOP) elevation in patients receiving intravitreal bevacizumab. Patients and methods This study included 52 patients with diabetic retinopathy between 28 to 75 years of age with a mean age of 51 years; 30 (58%) were females, and 22 (42%) were males. All patients received bevacizumab (1.25 mg/0.05 mL) injected intravitreally in a standard fashion between May 2012 to February 2013 in the AL-Jumhoury teaching hospital. IOP was measured at baseline, 5, 10, and 30 minutes after injection using Goldman applanation tonometry. Statistics Data were analyzed using the SPSS v.12.0 for windows. Basic, demographic, and clinical data were analyzed using means, proportions, and appropriate 95% confidence intervals (CIs). Results Most patients (85%) were diagnosed with proliferative diabetic retinopathy, while 15% presented with diabetic macular edema. The mean IOP values at baseline, 5, 10, and 30 minutes after injection were 14.0 mmHg (95% CI 13.4–14.7), 36.1 mmHg (95% CI 33.5–38.6), 25.7 mmHg (95% CI 23.8–27.5), and 15.5 mmHg (95% CI 12.4–16.51), respectively. Regression analysis showed a trend toward phakic patients having higher IOP at 30 minutes. Conclusion Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all IOP returned to a safe range (<25 mmHg) within 30 minutes. Elevated IOP 30 minutes after injection only occurs rarely, so routine prophylactic use of anti-glaucoma medication is not indicated. PMID:24707164

  3. The Negative Relationship between Bilirubin Level and Diabetic Retinopathy: A Meta-Analysis

    PubMed Central

    Wu, Xiaomei; Ning, Kang; Jiang, Feng; Zhang, Lu

    2016-01-01

    Objectives Findings on the relationship between total bilirubin level (TBL) and diabetic retinopathy (DR) are inconsistent. Thus, we carried out a meta-analysis to investigate the relationship between TBL and the risk of DR. Methods Relevant studies were selected from six databases up to 31 May 2016 using a search strategy. The relevant data were extracted from the included studies according to the inclusion and exclusion criteria, and the mean value with standard errors or odds ratio (OR) with 95% confidence intervals (CIs) were calculated. We compared TBL in patients with DR with that in patients with diabetes but without retinopathy (NDR), and analyzed the dose-response relationship between TBL and the risk of DR. Results Twenty-four studies were selected in this meta-analysis. Twenty studies were included to calculate the pooled SMD, and the results showed that TBL in the DR group was lower than that in the NDR group (SMD: –0.52, 95% CI: –0.67, –0.38). Nine studies were included to calculate the pooled ORs, and the results showed that there was a significant negative relationship between TBL and the risk of DR (OR: 0.19, 95% CI: 0.14, 0.25). Six studies were included to investigate the dose-response relationship between TBL and the risk of DR, and we found a nonlinear relationship between TBL and the risk of DR. The results of our meta-analysis were found to be reliable using subgroup and sensitivity analyses. Conclusions The results of our meta-analysis indicate that higher TBL may be protective against DR in subjects with diabetes, and TBL could be used as a biomarker to predict the risk of DR. PMID:27571522

  4. Design of Content Based Image Retrieval Scheme for Diabetic Retinopathy Images using Harmony Search Algorithm.

    PubMed

    Sivakamasundari, J; Natarajan, V

    2015-01-01

    Diabetic Retinopathy (DR) is a disorder that affects the structure of retinal blood vessels due to long-standing diabetes mellitus. Automated segmentation of blood vessel is vital for periodic screening and timely diagnosis. An attempt has been made to generate continuous retinal vasculature for the design of Content Based Image Retrieval (CBIR) application. The typical normal and abnormal retinal images are preprocessed to improve the vessel contrast. The blood vessels are segmented using evolutionary based Harmony Search Algorithm (HSA) combined with Otsu Multilevel Thresholding (MLT) method by best objective functions. The segmentation results are validated with corresponding ground truth images using binary similarity measures. The statistical, textural and structural features are obtained from the segmented images of normal and DR affected retina and are analyzed. CBIR in medical image retrieval applications are used to assist physicians in clinical decision-support techniques and research fields. A CBIR system is developed using HSA based Otsu MLT segmentation technique and the features obtained from the segmented images. Similarity matching is carried out between the features of query and database images using Euclidean Distance measure. Similar images are ranked and retrieved. The retrieval performance of CBIR system is evaluated in terms of precision and recall. The CBIR systems developed using HSA based Otsu MLT and conventional Otsu MLT methods are compared. The retrieval performance such as precision and recall are found to be 96% and 58% for CBIR system using HSA based Otsu MLT segmentation. This automated CBIR system could be recommended for use in computer assisted diagnosis for diabetic retinopathy screening. PMID:25996728

  5. Regenerative Therapeutic Potential of Adipose Stromal Cells in Early Stage Diabetic Retinopathy

    PubMed Central

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O.; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S.; March, Keith L.

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

  6. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy.

    PubMed

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S; March, Keith L

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved "b" wave amplitude (as measured by electroretinogram) within 1-3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

  7. Pericyte Chemomechanics and the Angiogenic Switch: Insights Into the Pathogenesis of Proliferative Diabetic Retinopathy?

    PubMed Central

    Durham, Jennifer T.; Dulmovits, Brian M.; Cronk, Stephen M.; Sheets, Anthony R.; Herman, Ira M.

    2015-01-01

    accompanying proliferative diabetic retinopathy. PMID:26030100

  8. Genetic Investigation of Complement Pathway Genes in Type 2 Diabetic Retinopathy: An Inflammatory Perspective

    PubMed Central

    Yang, Ming Ming; Wang, Jun; Ren, Hong; Sun, Yun Duan; Fan, Jiao Jie; Teng, Yan; Li, Yan Bo

    2016-01-01

    Diabetic retinopathy (DR) has complex multifactorial pathogenesis. This study aimed to investigate the association of complement pathway genes with susceptibility to DR. Eight haplotype-tagging SNPs of SERPING1 and C5 were genotyped in 570 subjects with type 2 diabetes: 295 DR patients (138 nonproliferative DR [NPDR] and 157 proliferative DR [PDR]) and 275 diabetic controls. Among the six C5 SNPs, a marginal association was first detected between rs17611 and total DR patients (P = 0.009, OR = 0.53 for recessive model). In stratification analysis, a significant decrease in the frequencies of G allele and GG homozygosity for rs17611 was observed in PDR patients compared with diabetic controls (Pcorr = 0.032, OR = 0.65 and Pcorr = 0.016, OR = 0.37, resp.); it was linked with a disease progression. A haplotype AA defined by the major alleles of rs17611 and rs1548782 was significantly predisposed to PDR with increased risk of 1.54 (Pcorr = 0.023). Regarding other variants in C5 and SERPING1, none of the tagging SNPs had a significant association with DR and its subgroups (all P > 0.05). Our study revealed an association between DR and C5 polymorphisms with clinical significance, whereas SERPING1 is not a major genetic component of DR. Our data suggest a link of complement pathway with DR pathogenesis. PMID:26989329

  9. Serum Cystatin C, Markers of Chronic Kidney Disease, and Retinopathy in Persons with Diabetes

    PubMed Central

    Wong, Chee Wai; Teo, Boon Wee; Lamoureux, Ecosse; Ikram, Mohammad Kamran; Wang, Jie Jin; Tai, E. Shyong; Sethi, Sunil; Wong, Tien Yin; Sabanayagam, Charumathi

    2015-01-01

    Purpose. We examined the association of CKD defined by serum creatinine, serum cystatin C, and albuminuria with moderate diabetic retinopathy (DR). Methods. We examined 1,119 Indian adults with diabetes, aged 40–80 years, who participated in the Singapore Indian Eye Study (2007–2009), a population-based cross-sectional study. The associations of CKD defined by each of the three markers alone and in combination with moderate DR were examined using logistic regression models adjusted for potential confounding factors including duration of diabetes, smoking, body mass index, systolic blood pressure, and HbA1c. Results. The prevalence of moderate DR was significantly higher among those with CKD defined by triple markers (41.1%) compared to CKD defined separately by creatinine (26.6%), cystatin C (20.9%), and albuminuria (23.4%). People with CKD defined by triple markers had a fourteenfold higher odds of moderate DR (OR (95% CI) = 13.63 (6.08–30.54)) compared to those without CKD by any marker. Nearly half (48.7%) of participants with cystatin C ≥ 1.12 mg/L have moderate DR. Conclusions. CKD defined by a triple marker panel was strongly associated with moderate DR in this Asian population with diabetes. PMID:26576434

  10. Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus

    PubMed Central

    Aydin, Erdinc; Sahin, Semsettin

    2016-01-01

    AIM To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. METHODS Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57±2.67 pg/mL (range 15.20-23.06) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79±2.56 pg/mL (range 9.80-20.10) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37±1.74 pg/mL (range 2.85-8.65) vs 6.11±1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11±1.90 pg/mL (range 3.13-9.41) vs control 6.15±1.91 pg/mL (range 2.18-9.86); PDR (5.37±1.74 pg/mL (range 2.85-8.65) vs control 6.15±1.91 pg/mL (range 2.18-9.86), P=0.808, P=0.264]. CONCLUSION Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity. PMID:27275429

  11. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina

    PubMed Central

    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M.; Bennis, Mohamed

    2016-01-01

    Purpose Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. Methods To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17×1014 photons/cm2/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT–PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). Results We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c-fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2

  12. Constructing Benchmark Databases and Protocols for Medical Image Analysis: Diabetic Retinopathy

    PubMed Central

    Kauppi, Tomi; Kämäräinen, Joni-Kristian; Kalesnykiene, Valentina; Sorri, Iiris; Uusitalo, Hannu; Kälviäinen, Heikki

    2013-01-01

    We address the performance evaluation practices for developing medical image analysis methods, in particular, how to establish and share databases of medical images with verified ground truth and solid evaluation protocols. Such databases support the development of better algorithms, execution of profound method comparisons, and, consequently, technology transfer from research laboratories to clinical practice. For this purpose, we propose a framework consisting of reusable methods and tools for the laborious task of constructing a benchmark database. We provide a software tool for medical image annotation helping to collect class label, spatial span, and expert's confidence on lesions and a method to appropriately combine the manual segmentations from multiple experts. The tool and all necessary functionality for method evaluation are provided as public software packages. As a case study, we utilized the framework and tools to establish the DiaRetDB1 V2.1 database for benchmarking diabetic retinopathy detection algorithms. The database contains a set of retinal images, ground truth based on information from multiple experts, and a baseline algorithm for the detection of retinopathy lesions. PMID:23956787

  13. Estimating the proportion of persons with diabetes developing diabetic retinopathy in India: A systematic review and meta-analysis

    PubMed Central

    Jotheeswaran, A. T.; Lovakanth, Nukala; Nadiga, Shruthi; Anchala, Raghupathy; Murthy, G. V. S.; Gilbert, Clare E.

    2016-01-01

    Background: Available evidence from India shows that the control of diabetes is poor in majority of the population. This escalates the risk of complications. There is no systematic review to estimate the magnitude of diabetic retinopathy (DR) in India. Materials and Methods: A systematic literature search was carried out in Ovid Medline and EMBASE databases using Mesh and key search terms. Studies which reported the proportion of people with diabetes with DR in a representative community population were included. Two independent reviewers reviewed all the retrieved publications. Data were extracted using a predefined form. Review Manager software was used to perform meta-analysis to provide a pooled estimate. Studies included were assessed for methodological quality using selected items from the STROBE checklist. Results: Seven studies (1999–2014; n = 8315 persons with diabetes) were included in the review. In the meta-analysis, 14.9% (95% confidence interval [CI] 10.7–19.0%) of known diabetics aged ≥30 years and 18.1% (95% CI 14.8–21.4) among those aged ≥50 years had DR. Heterogeneity around this estimate ranged from I2= 79–87%. No linear trend was observed between age and the proportion with DR. The overall methodological quality of included studies was moderate. Conclusions: Early detection of DR is currently not prioritized in public health policies for noncommunicable diseases and blindness programs. Methodological issues in studies suggest that the proportion of diabetics with DR is underestimated in the Indian population. Future research should emphasize more robust methodology for assessing diabetes and DR status. PMID:27144137

  14. Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy

    PubMed Central

    Canton, A.; Burgos, R.; Hernandez, C.; Mateo, C.; Segura, R.; Mesa, J.; Simo, R.

    2000-01-01

    BACKGROUND—Hepatocyte growth factor (HGF) is an endothelium specific growth factor that has been implicated in angiogenesis, a crucial event for the development of proliferative diabetic retinopathy (PDR). The aim of the study is to determine the intravitreous concentrations of HGF in diabetic patients with PDR, and to investigate whether its serum levels could contribute to its intravitreous concentration.
METHODS—17 diabetic patients and seven non-diabetic patients in whom a vitrectomy was performed were studied. Both groups were matched by serum levels of HGF. Venous blood and vitreous samples were collected simultaneously at the time of vitreoretinal surgery. Vitreous and serum HGF were determined by ELISA.
RESULTS—Intravitreous concentrations of HGF (median and range) were higher in diabetic patients (17.04 ng/ml (9.98-80)) in comparison with non-diabetic patients (5.88 ng/ml (2.57-14.20); p=0.003). Intravitreous HGF concentrations were strikingly higher than serum HGF concentrations both in diabetic patients (17.04 ng/ml (9.98-80) v 0.66 ng/ml (0.26-1.26); p<0.001) and in the control group (5.88 ng/ml (2.57-14.20) v 0.68 ng/ml (0.49-0.96); p=0.003). No correlation was found between serum and vitreous levels of HGF in both groups (diabetic patients, r= −0.31; p=0.5 and control subjects r= −0.15; p=0.5).
CONCLUSION—The high vitreous levels of HGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis appears to be the main contributing factor for the high vitreous HGF concentrations in diabetic patients, a cytokine that seems to be directly involved in the pathogenesis of PDR.

 PMID:10873984

  15. Animal models of diabetic retinopathy: doors to investigate pathogenesis and potential therapeutics

    PubMed Central

    2013-01-01

    Effective and validated animal models are valuable to investigate the pathogenesis and potential therapeutics for human diseases. There is much concern for diabetic retinopathy (DR) in that it affects substantial number of working population all around the world, resulting in visual deterioration and social deprivation. In this review, we discuss animal models of DR based on different species of animals from zebrafish to monkeys and prerequisites for animal models. Despite criticisms on imprudent use of laboratory animals, we hope that animal models of DR will be appropriately utilized to deepen our understanding on the pathogenesis of DR and to support our struggle to find novel therapeutics against catastrophic visual loss from DR. PMID:23786217

  16. Variability in grading diabetic retinopathy from stereo fundus photographs: comparison of physician and lay readers.

    PubMed Central

    Milton, R. C.; Ganley, J. P.; Lynk, R. H.

    1977-01-01

    Two physicians and two lay readers were trained according to a detailed protocol in the grading of 17 lesions found in diabetic retinopathy by evaluation of stereo fundus photographs according to a modified Airlie House classification. Intraobserver and interobserver variability of these readers was assessed by two methods: weighted kappa, and frequency of agreement within one grade. In general, physician readers were found to be less variable on replicate readings than were lay leaders, and had slightly better agreement with each other than with the lay readers. The physiological significance of the direction and magnitude of the difference between physician and lay reader variability for individual lesions was often uncertain. Assessment of contribution to disagreement by individual readers was possible and permits future training directed at reducing disagreement to acceptable values. PMID:851521

  17. Feasibility of level-set analysis of enface OCT retinal images in diabetic retinopathy

    PubMed Central

    Mohammad, Fatimah; Ansari, Rashid; Wanek, Justin; Francis, Andrew; Shahidi, Mahnaz

    2015-01-01

    Pathology segmentation in retinal images of patients with diabetic retinopathy is important to help better understand disease processes. We propose an automated level-set method with Fourier descriptor-based shape priors. A cost function measures the difference between the current and expected output. We applied our method to enface images generated for seven retinal layers and determined correspondence of pathologies between retinal layers. We compared our method to a distance-regularized level set method and show the advantages of using well-defined shape priors. Results obtained allow us to observe pathologies across multiple layers and to obtain metrics that measure the co-localization of pathologies in different layers. PMID:26137390

  18. LSFG findings of proliferative diabetic retinopathy after intravitreal injection of bevacizumab.

    PubMed

    Enaida, Hiroshi; Okamoto, Kenji; Fujii, Hitoshi; Ishibashi, Tatsuro

    2010-01-01

    The authors investigate the changes of chorioretinal blood flow using laser speckle flowgraphy (LSFG) in efficacy of treatment. Intravitreal bevacizumab was injected in a patient with proliferative diabetic retinopathy. LSFG measures the relative velocity index of erythrocytes (mean blur rate) in a previously confirmed area, with neovascularization elsewhere (NVE), neovascularization of the disc (NVD), and without neovascularization. The authors compared mean blur rate before and after bevacizumab injection in each area. In LSFG images, regression of blood flow was observed at the area of neovascularization sequentially as the change of color pattern. Finally, decrease of the mean blur rate of an average 32.7% was observed in the NVE area. Similarly, a reduction of 31.9% of mean blur rate was observed in the NVD area. However, in the area of without neovascularization, reduction of mean blur rate was not observed. This suggested the useful possibility of measuring chorioretinal blood flow changes by drug intervention using LSFG analysis. PMID:21117574

  19. LSFG findings of proliferative diabetic retinopathy after intravitreal injection of bevacizumab.

    PubMed

    Enaida, Hiroshi; Okamoto, Kenji; Fujii, Hitoshi; Ishibashi, Tatsuro

    2010-01-01

    The authors investigate the changes of chorioretinal blood flow using laser speckle flowgraphy (LSFG) in efficacy of treatment. Intravitreal bevacizumab was injected in a patient with proliferative diabetic retinopathy. LSFG measures the relative velocity index of erythrocytes (mean blur rate) in a previously confirmed area, with neovascularization elsewhere (NVE), neovascularization of the disc (NVD), and without neovascularization. The authors compared mean blur rate before and after bevacizumab injection in each area. In LSFG images, regression of blood flow was observed at the area of neovascularization sequentially as the change of color pattern. Finally, decrease of the mean blur rate of an average 32.7% was observed in the NVE area. Similarly, a reduction of 31.9% of mean blur rate was observed in the NVD area. However, in the area of without neovascularization, reduction of mean blur rate was not observed. This suggested the useful possibility of measuring chorioretinal blood flow changes by drug intervention using LSFG analysis. PMID:22785537

  20. Oscillation of Angiogenesis with Vascular Dropout in Diabetic Retinopathy by VESsel GENeration Analysis (VESGEN)

    PubMed Central

    Parsons-Wingerter, Patricia; Radhakrishnan, Krishnan; Vickerman, Mary B.; Kaiser, Peter K.

    2010-01-01

    Purpose. Vascular dropout and angiogenesis are hallmarks of the progression of diabetic retinopathy (DR). However, current evaluation of DR relies on grading of secondary vascular effects, such as microaneurysms and hemorrhages, by clinical examination instead of by evaluation of actual vascular changes. The purpose of this study was to map and quantify vascular changes during progression of DR by VESsel GENeration Analysis (VESGEN). Methods. In this prospective cross-sectional study, 15 eyes with DR were evaluated with fluorescein angiography (FA) and color fundus photography, and were graded using modified Early Treatment Diabetic Retinopathy Study criteria. FA images were separated by semiautomatic image processing into arterial and venous trees. Vessel length density (Lv), number density (Nv), and diameter (Dv) were analyzed in a masked fashion with VESGEN software. Each vascular tree was automatically segmented into branching generations (G1…G8 or G9) by vessel diameter and branching. Vascular remodeling status (VRS) for Nv and Lv was graded 1 to 4 for increasing severity of vascular change. Results. By Nv and Lv, VRS correlated significantly with the independent clinical diagnosis of mild to proliferative DR (13/15 eyes). Nv and Lv of smaller vessels (G≥6) increased from VRS1 to VRS2 by 2.4 × and 1.6×, decreased from VRS2 to VRS3 by 0.4 × and 0.6×, and increased from VRS3 to VRS4 by 1.7 × and 1.5 × (P < 0.01). Throughout DR progression, the density of larger vessels (G1–5) remained essentially unchanged, and Dv1–5 increased slightly. Conclusions. Vessel density oscillated with the progression of DR. Alternating phases of angiogenesis/neovascularization and vascular dropout were dominated first by remodeling of arteries and subsequently by veins. PMID:19797226

  1. Aflibercept Traps Galectin-1, an Angiogenic Factor Associated with Diabetic Retinopathy.

    PubMed

    Kanda, Atsuhiro; Noda, Kousuke; Saito, Wataru; Ishida, Susumu

    2015-01-01

    Vascular endothelial growth factor (VEGF)-A-driven angiogenesis contributes to various disorders including cancer and proliferative diabetic retinopathy (PDR). Among several VEGF-A blockers clinically used is aflibercept, a chimeric VEGFR1/VEGFR2-based decoy receptor fused to the Fc fragment of IgG1 (i.e., VEGFR1/VEGFR2-Fc). Here, we revealed a novel anti-angiogenic function for aflibercept beyond its antagonism against VEGF family members. Immunoprecipitation and mass spectrometry analyses identified galectin-1 as an aflibercept-interacting protein. Biolayer interferometry revealed aflibercept binding to galectin-1 with higher affinity than VEGFR1-Fc and VEGFR2-Fc, which was abolished by deglycosylation of aflibercept with peptide:N-glycosidase F. Retinal LGALS1/Galectin-1 mRNA expression was enhanced in vitro by hypoxic stimulation and in vivo by induction of diseases including diabetes. Galectin-1 immunoreactivity co-localized with VEGFR2 in neovascular tissues surgically excised from human eyes with PDR. Compared with non-diabetic controls, intravitreal galectin-1 protein levels were elevated in PDR eyes, showing no correlation with increased VEGF-A levels. Preoperative injection of bevacizumab, a monoclonal antibody to VEGF-A, reduced the VEGF-A, but not galectin-1, levels. Galectin-1 application to human retinal microvascular endothelial cells up-regulated VEGFR2 phosphorylation, which was eliminated by aflibercept. Our present findings demonstrated the neutralizing efficacy of aflibercept against galectin-1, an angiogenic factor associated with PDR independently of VEGF-A. PMID:26648523

  2. A diabetic retinopathy detection method using an improved pillar K-means algorithm.

    PubMed

    Gogula, Susmitha Valli; Divakar, Ch; Satyanarayana, Ch; Rao, Allam Appa

    2014-01-01

    The paper presents a new approach for medical image segmentation. Exudates are a visible sign of diabetic retinopathy that is the major reason of vision loss in patients with diabetes. If the exudates extend into the macular area, blindness may occur. Automated detection of exudates will assist ophthalmologists in early diagnosis. This segmentation process includes a new mechanism for clustering the elements of high-resolution images in order to improve precision and reduce computation time. The system applies K-means clustering to the image segmentation after getting optimized by Pillar algorithm; pillars are constructed in such a way that they can withstand the pressure. Improved pillar algorithm can optimize the K-means clustering for image segmentation in aspects of precision and computation time. This evaluates the proposed approach for image segmentation by comparing with Kmeans and Fuzzy C-means in a medical image. Using this method, identification of dark spot in the retina becomes easier and the proposed algorithm is applied on diabetic retinal images of all stages to identify hard and soft exudates, where the existing pillar K-means is more appropriate for brain MRI images. This proposed system help the doctors to identify the problem in the early stage and can suggest a better drug for preventing further retinal damage. PMID:24516323

  3. A diabetic retinopathy detection method using an improved pillar K-means algorithm

    PubMed Central

    Gogula, Susmitha valli; Divakar, CH; Satyanarayana, CH; Rao, Allam Appa

    2014-01-01

    The paper presents a new approach for medical image segmentation. Exudates are a visible sign of diabetic retinopathy that is the major reason of vision loss in patients with diabetes. If the exudates extend into the macular area, blindness may occur. Automated detection of exudates will assist ophthalmologists in early diagnosis. This segmentation process includes a new mechanism for clustering the elements of high-resolution images in order to improve precision and reduce computation time. The system applies K-means clustering to the image segmentation after getting optimized by Pillar algorithm; pillars are constructed in such a way that they can withstand the pressure. Improved pillar algorithm can optimize the K-means clustering for image segmentation in aspects of precision and computation time. This evaluates the proposed approach for image segmentation by comparing with Kmeans and Fuzzy C-means in a medical image. Using this method, identification of dark spot in the retina becomes easier and the proposed algorithm is applied on diabetic retinal images of all stages to identify hard and soft exudates, where the existing pillar K-means is more appropriate for brain MRI images. This proposed system help the doctors to identify the problem in the early stage and can suggest a better drug for preventing further retinal damage. PMID:24516323

  4. Addressing risk factors, screening, and preventative treatment for diabetic retinopathy in developing countries: a review.

    PubMed

    Lin, Stephanie; Ramulu, Pradeep; Lamoureux, Ecosse L; Sabanayagam, Charumathi

    2016-05-01

    The number of people with diabetic retinopathy (DR) has increased with the increasing prevalence of diabetes mellitus worldwide, especially in developing countries. In recent years, the successful implementation of public health programs in developed countries has been thought to contribute to decreases in blindness from DR. Developing countries, however, have not seen the same improvements, and their public health interventions still face significant challenges. In this review we describe the current state of public health approaches including risk factor control, screening and treatment techniques for DR in developing countries, and suggest recommendations. While the awareness of DR is variable, specific knowledge about DR is low, such that many patients have already experienced vision loss by the time they are screened. Attempts to improve rates of screening, in particular through non-mydriatic cameras and tele-screening, are ongoing and promising, although challenges include collaboration with healthcare systems and technology failures. Laser treatment is the most readily available, with anti-VEGF therapy and vitreo-retinal surgery increasingly sought after and provided. Recommendations include the use of 'targeted mydriasis' for fundus imaging to address high rates of ungradable images, increased communication with diabetes management services to improve patient retention and mobilization of access to DR treatments. PMID:26991970

  5. Functions of Müller cell-derived vascular endothelial growth factor in diabetic retinopathy

    PubMed Central

    Wang, Juan-Juan; Zhu, Meili; Le, Yun-Zheng

    2015-01-01

    Müller cells are macroglia and play many essential roles as supporting cells in the retina. To respond to pathological changes in diabetic retinopathy (DR), a major complication in the eye of diabetic patients, retinal Müller glia produce a high level of vascular endothelial growth factor (VEGF or VEGF-A). As VEGF is expressed by multiple retinal cell-types and Müller glia comprise only a small portion of cells in the retina, it has been a great challenge to reveal the function of VEGF or other globally expressed proteins produced by Müller cells. With the development of conditional gene targeting tools, it is now possible to dissect the function of Müller cell-derived VEGF in vivo. By using conditional gene targeting approach, we demonstrate that Müller glia are a major source of retinal VEGF in diabetic mice and Müller cell-derived VEGF plays a significant role in the alteration of protein expression and peroxynitration, which leads to retinal inflammation, neovascularization, vascular leakage, and vascular lesion, key pathological changes in DR. Therefore, Müller glia are a potential cellular target for the treatment of DR, a leading cause of blindness. PMID:26069721

  6. A Hybrid PSO-DEFS Based Feature Selection for the Identification of Diabetic Retinopathy.

    PubMed

    Balakrishnan, Umarani; Venkatachalapathy, Krishnamurthi; Marimuthu, Girirajkumar S

    2015-01-01

    Diabetic Retinopathy (DR) is an eye disease, which may cause blindness by the upsurge of insulin in blood. The major cause of visual loss in diabetic patient is macular edema. To diagnose and follow up Diabetic Macular Edema (DME), a powerful Optical Coherence Tomography (OCT) technique is used for the clinical assessment. Many existing methods found out the DME affected patients by estimating the fovea thickness. These methods have the issues of lower accuracy and higher time complexity. In order to overwhelm the above limitations, a hybrid approaches based DR detection is introduced in the proposed work. At first, the input image is preprocessed using green channel extraction and median filter. Subsequently, the features are extracted by gradient-based features like Histogram of Oriented Gradient (HOG) with Complete Local Binary Pattern (CLBP). The texture features are concentrated with various rotations to calculate the edges. We present a hybrid feature selection that combines the Particle Swarm Optimization (PSO) and Differential Evolution Feature Selection (DEFS) for minimizing the time complexity. A binary Support Vector Machine (SVM) classifier categorizes the 13 normal and 75 abnormal images from 60 patients. Finally, the patients affected by DR are further classified by Multi-Layer Perceptron (MLP). The experimental results exhibit better performance of accuracy, sensitivity, and specificity than the existing methods. PMID:25817547

  7. The association analysis polymorphism of CDKAL1 and diabetic retinopathy in Chinese Han population

    PubMed Central

    Liu, Nai-Jia; Xiong, Qian; Wu, Hui-Hui; Li, Yan-Liang; Yang, Zhen; Tao, Xiao-Ming; Du, Yan-Ping; Lu, Bin; Hu, Ren-Ming; Wang, Xuan-Chun; Wen, Jie

    2016-01-01

    AIM To identify the contribution of CDKAL1 to the development of diabetic retinopathy (DR) in Chinese population. METHODS A case-control study was performed to investigate the genetic association between DR and polymorphic variants of CDKAL1 in Chinese Han population with type 2 diabetes mellitus (T2DM). A well-defined population with T2DM, consisting of 475 controls and 105 DR patients, was recruited. All subjects were genotyped for the genetic variant (rs10946398) of CDKAL1. Genotyping was performed by iPLEX technology. The association between rs10946398 and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis. RESULTS There were significant differences in C allele frequencies of rs10946398 (CDKAL1) between control and DR groups (45.06% versus 55.00%, P<0.05). The rs10946398 of CDKAL1 was found to be associated with the increased risk of DR among patients with diabetes. CONCLUSION Our findings suggest that rs10946398 of CDKAL1 is independently associated with DR in a Chinese Han population. PMID:27275426

  8. Retrobulbar blood flow changes in eyes with diabetic retinopathy: a 10-year follow-up study

    PubMed Central

    Neudorfer, Meira; Kessner, Rivka; Goldenberg, Dafna; Lavie, Anat; Kessler, Ada

    2014-01-01

    Purpose We sought to assess long-term changes in the flow parameters of retrobulbar vessels in diabetic patients. Methods The retrobulbar circulation of 138 eyes was evaluated between 1994 and 1995 and 36 eyes were reevaluated between 2004 and 2008 (study group). They were divided into four groups: eyes of diabetic patients without diabetic retinopathy (DR), eyes with nonproliferative DR, eyes with proliferative DR, and eyes of nondiabetic patients (controls). Color Doppler imaging was used to assess the flow velocities in the major retrobulbar vessels. The resistive index (RI) was calculated and compared among the groups and between the two time periods. Results RI values of the central retinal artery and posterior ciliary artery had increased in the two non-DR groups and in the nonproliferative DR group, with a surprising decrease measured in eyes with proliferative DR (P= nonsignificant [NS]). Combining the nonproliferative DR and proliferative DR groups resulted in a milder increase of the RI of the posterior ciliary artery (P= NS) and the central retinal artery (P=0.02) in the DR group compared to the other groups. Conclusion Our results demonstrate that an increase of the resistance in the retrobulbar vessels, as a part of DR, can lessen over time and may even be reversed. PMID:25473257

  9. Aflibercept Traps Galectin-1, an Angiogenic Factor Associated with Diabetic Retinopathy

    PubMed Central

    Kanda, Atsuhiro; Noda, Kousuke; Saito, Wataru; Ishida, Susumu

    2015-01-01

    Vascular endothelial growth factor (VEGF)-A-driven angiogenesis contributes to various disorders including cancer and proliferative diabetic retinopathy (PDR). Among several VEGF-A blockers clinically used is aflibercept, a chimeric VEGFR1/VEGFR2-based decoy receptor fused to the Fc fragment of IgG1 (i.e., VEGFR1/VEGFR2-Fc). Here, we revealed a novel anti-angiogenic function for aflibercept beyond its antagonism against VEGF family members. Immunoprecipitation and mass spectrometry analyses identified galectin-1 as an aflibercept-interacting protein. Biolayer interferometry revealed aflibercept binding to galectin-1 with higher affinity than VEGFR1-Fc and VEGFR2-Fc, which was abolished by deglycosylation of aflibercept with peptide:N-glycosidase F. Retinal LGALS1/Galectin-1 mRNA expression was enhanced in vitro by hypoxic stimulation and in vivo by induction of diseases including diabetes. Galectin-1 immunoreactivity co-localized with VEGFR2 in neovascular tissues surgically excised from human eyes with PDR. Compared with non-diabetic controls, intravitreal galectin-1 protein levels were elevated in PDR eyes, showing no correlation with increased VEGF-A levels. Preoperative injection of bevacizumab, a monoclonal antibody to VEGF-A, reduced the VEGF-A, but not galectin-1, levels. Galectin-1 application to human retinal microvascular endothelial cells up-regulated VEGFR2 phosphorylation, which was eliminated by aflibercept. Our present findings demonstrated the neutralizing efficacy of aflibercept against galectin-1, an angiogenic factor associated with PDR independently of VEGF-A. PMID:26648523

  10. Prevalence and causes of blindness and diabetic retinopathy in Southern Saudi Arabia

    PubMed Central

    Hajar, Saad; Hazmi, Ali Al; Wasli, Mustafa; Mousa, Ahmed; Rabiu, Mansour

    2015-01-01

    Objectives: To determine the prevalence and causes of blindness and diabetic retinopathy (DR) in Jazan district, Southern Saudi Arabia. Methods: Using the standardized Rapid Assessment for Avoidable Blindness (RAAB) and DR cross-sectional methodology, 3800 subjects were randomly selected from the population of ≥50 years of age in Jazan, Saudi Arabia between November 2011 and January 2012. Participants underwent screening comprised of interview, random blood glucose test, and ophthalmic assessment including visual acuity (VA) and fundus examination. Among participants with VA <6/18 in either eye, the cause(s) of visual impairment was determined. Participants were classified as diabetic if they had previous diagnoses of diabetes, or random blood glucose >200 mg/dl. Diabetic participants were assessed for DR using dilated fundus examination. All data were recorded using the RAAB + DR standardized forms. Results: The prevalence of bilateral blindness <3/60 was 3.3% (95% confidence interval [CI]: 2.74 - 3.90). Cataract was the leading cause of blindness (58.6%); followed by posterior segment diseases (20%), which included DR (7; 3.3%). The prevalence of diabetes mellitus (DM) was 22.4%, (95% CI: 21.09 - 23.79), among them; 27.8% had DR. The prevalence of sight-threatening DR was 5.7%. Conclusion: The prevalence of DM and the corresponding proportion of DR in this region is lower than that reported in other regions of Saudi Arabia. However, the prevalence of blindness not related to DR is relatively higher than the other studies. PMID:25828282

  11. Dietary intake of lutein and diabetic retinopathy in the Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Sahli, Michelle W.; Mares, Julie A.; Meyers, Kristin J.; Klein, Ronald; Brady, William E.; Klein, Barbara E. K.; Ochs-Balcom, Heather M.; Donahue, Richard P.

    2016-01-01

    Purpose We tested the hypothesis that dietary intake of lutein is inversely associated with prevalence of diabetic retinopathy due to its antioxidant and anti-inflammatory properties and its location within the retina. Methods We used logistic regression to examine the association between prevalent DR and energy-adjusted lutein intake [by quartile (Q)] using data collected from 1,430 ARIC study participants with diabetes (n=994 White and n=508 Black). DR was assessed using a 45-degree nonmydriatic retinal photograph from one randomly chosen eye taken at visit 3 (1993–95). Dietary lutein intake was estimated using a 66-item food frequency questionnaire at visit 1(1987–89). Results The median estimated daily lutein intake was 1,370 μg/1000 kcals and the prevalence of DR was ~21%. We found a crude association between lutein and DR [OR (95% CI) for Q4 (high intake) vs. Q1 (low intake) =2.11 (1.45–3.09); p for trend<0.0001] which was attenuated after adjustment for race, duration of diabetes, glycosylated hemoglobin levels, field center and energy intake [1.41 (0.87–2.28); p for trend=0.01]. In analyses limited to persons with a short duration of diabetes (<6 years), the association no longer persisted [0.94 (0.31–2.16); p for trend=0.72] as compared to the association in those with a longer duration of diabetes (≥6 year) [1.58 (0.91–2.75); p for trend=0.01]. Conclusion Contrary to our hypothesis, we found that the odds of higher lutein intake were greater among those with DR than those without DR. However, after adjusting for confounders, intake of lutein was not associated with DR. PMID:26949989

  12. Anti-inflammatory role of sesamin in STZ induced mice model of diabetic retinopathy.

    PubMed

    Ahmad, Saif; ElSherbiny, Nehal M; Jamal, Mohammad Sarwar; Alzahrani, Faisal A; Haque, Rizwanul; Khan, Raziuddin; Zaidi, Syed Kashif; AlQahtani, Mohammed H; Liou, Gregory I; Bhatia, Kanchan

    2016-06-15

    Diabetic retinopathy (DR) is the common cause of diabetic vascular complications that leads to the blindness in the working age population throughout the world. Free radicals mediated oxidative stress and inflammation play a significant role in pathophysiology of DR. To find a new and safe drug to treat DR is still challenging and for that purpose the natural compounds may be therapeutic agents. Here we show that sesamin (SES), which is the main component of sesame seed and its oil, and has been reported as potent antioxidant and neuroprotective, could be a therapeutic agent in DR. In the present study, we investigated protective effect of SES in Streptozotocin (STZ) induced DR in mice. The mice were divided into three groups (Control, DR and DR+SES) for the study. After two weeks post-diabetic establishment, mice were treated with SES (30mg/kg BW, i.p, alternate day) for four weeks. Mice body weight and blood glucose level were measured from each group. The microglial activation of retina was determined by immunohistochemistry analysis by using Iba-1 as a microglia marker. Retinal mRNA levels of Iba-1, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and Intercellular Adhesion Molecule 1 (ICAM-1) were examined by qRT-PCR. The level of iNOS protein expression was examined by immunoblotting. Together these data demonstrate that SES treatment lowered the progression of diabetic retinal injury by: 1) decreasing blood glucose level, 2) suppressing microglia activation, 3) reducing retinal TNF-α and ICAM-1 levels and 4) quenching iNOS expression. In conclusion, the results suggest that SES treatment may be of therapeutic benefit in reducing the progression of DR by ameliorating hyperglycemia and inflammation in diabetic retina. PMID:27235348

  13. Benefits of Renin-Angiotensin Blockade on Retinopathy in Type 1 Diabetes Vary With Glycemic Control

    PubMed Central

    Harindhanavudhi, Tasma; Mauer, Michael; Klein, Ronald; Zinman, Bernard; Sinaiko, Alan; Caramori, M. Luiza

    2011-01-01

    OBJECTIVE Optimal glycemic control slows diabetic retinopathy (DR) development and progression and is the standard of care for type 1 diabetes. However, these glycemic goals are difficult to achieve and sustain in clinical practice. The Renin Angiotensin System Study (RASS) showed that renin-angiotensin system (RAS) blockade can slow DR progression. In the current study, we evaluate whether glycemic control influenced the benefit of RAS blockade on DR progression in type 1 diabetic patients. RESEARCH DESIGN AND METHODS We used RASS data to analyze the relationships between two-steps or more DR progression and baseline glycemic levels in 223 normotensive, normoalbuminuric type 1 diabetic patients randomized to receive 5 years of enalapril or losartan compared with placebo. RESULTS A total of 147 of 223 patients (65.9%) had DR at baseline (47 of 74 patients [63.5%] in placebo and 100 of 149 patients [67.1%] in the combined treatment groups [P = 0.67]). Patients with two-steps or more DR progression had higher baseline A1C than those without progression (9.4 vs. 8.2%, P < 0.001). There was no beneficial effect of RAS blockade (P = 0.92) in patients with baseline A1C ≤7.5%. In contrast, 30 of 112 (27%) patients on the active treatment arms with A1C >7.5% had two-steps or more DR progression compared with 26 of 56 patients (46%) in the placebo group (P = 0.03). CONCLUSIONS RAS blockade reduces DR progression in normotensive, normoalbuminuric type 1 diabetic patients with A1C >7.5%. Whether this therapy could benefit patients with A1C ≤7.5% will require long-term studies of much larger cohorts. PMID:21715517

  14. Proliferative retinopathy in type 1 diabetes is associated with cerebral microbleeds, which is part of generalized microangiopathy.

    PubMed

    Woerdeman, Jorn; van Duinkerken, Eelco; Wattjes, Mike P; Barkhof, Frederik; Snoek, Frank J; Moll, Annette C; Klein, Martin; de Boer, Michiel P; Ijzerman, Richard G; Serné, Erik H; Diamant, Michaela

    2014-04-01

    OBJECTIVE We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS Thirty-three patients with proliferative diabetic retinopathy (PDR+), 34 patients without proliferative diabetic retinopathy, and 33 controls underwent magnetic resonance imaging to assess cerebral microangiopathy (cerebral microbleeds) and ischemic damage (white matter hyperintensities and lacunes). Peripheral microvascular function, i.e., skin capillary density and capillary recruitment, was assessed by capillary microscopy. RESULTS Cerebral microbleeds, but not ischemic damage, were more prevalent in PDR+ patients versus the other groups (P < 0.05). A trend was found across groups for the lowest baseline capillary density in PDR+ patients (P for trend = 0.05). In individuals with microbleeds, capillary recruitment was impaired compared with those without microbleeds (P = 0.04). CONCLUSIONS In PDR+ patients, cerebral microbleed prevalence was higher and seems part of generalized microangiopathy that may affect the skin and the brain. PMID:24319122

  15. Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei-Yueh; Chen, Szu-Chia; Shin, Shyi-Jang; Hsiao, Pi-Jung; Lin, Kun-Der; Hsu, Wei-Hao

    2016-01-01

    Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015–1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084–1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM. PMID:27490538

  16. Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus.

    PubMed

    Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei-Yueh; Chen, Szu-Chia; Shin, Shyi-Jang; Hsiao, Pi-Jung; Lin, Kun-Der; Hsu, Wei-Hao

    2016-01-01

    Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM. PMID:27490538

  17. Magnitude and determinants of diabetic retinopathy among persons with diabetes registered at employee health department of a tertiary Eye Hospital of central Saudi Arabia

    PubMed Central

    Khandekar, Rajiv; Al Hassan, Arif; Al Dhibi, Hassan; Al Bahlal, Abdullah; Al-Futais, Muneera

    2015-01-01

    Background: To estimate the magnitude and determinants of diabetic retinopathy (DR) among persons with diabetes registered at the employee health department of King Khaled Eye Specialist Hospital (KKESH). Methods: A retrospective review of medical records was conducted in 2013–14 at KKESH. The case record review extracted demographic, profile of diabetes, diabetic complications, and different blood indices to determine the status of potential risk factors. Ocular profile, especially DR was also noted. Results: Our cohort had 94 staff with diabetes. Eye examination was carried out in 51 (54.8%) of them. The rate of DR was 52% (95% confidence interval (CI) 28–66). Sight-threatening diabetic retinopathy (STDR) (proliferative DR and/or diabetic macular edema) was present in 40% of those examined. Good glycemic control was noted in 42% of participants. Duration of diabetes was associated with DR (P = 0.04). Good glycemic control was negatively associated to DR (odds ratio = 0.2 [95% CI 0.04–0.6]). The coverage of eye screening was 55% only. Laser treatment was given to 80% of STDR cases. The lens opacity and glaucoma rate was 15% and 8.3%, respectively. Conclusions: Low coverage for eye screening and laser treatment to diabetics among the staff of an eye hospital is a matter of concern. The underlying causes of low coverage of screening, digital fundus photography as a screening tool and management should be addressed. PMID:26903721

  18. FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy

    PubMed Central

    Deliyanti, Devy; Zhang, Yuan; Khong, Fay; Berka, David R.; Stapleton, David I.; Kelly, Darren J.; Wilkinson-Berka, Jennifer L.

    2015-01-01

    Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011 would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension due to an overactive extra-renal renin-angiotensin system. Diabetic rats were studied for 8 and 32 weeks and received intravitreal injections of FT011 (50 μM) or vehicle (0.9% NaCl). Comparisons were to age-matched controls. In the 8-week study, retinal inflammation was examined by quantitating vascular leukocyte adherence, microglial/macrophage density and the expression of inflammatory mediators. Macroglial Müller cells, which exhibit a pro-inflammatory and pro-angiogenic phenotype in diabetes, were evaluated in the 8-week study as well as in culture following exposure to hyperglycaemia and FT011 (10, 30, 100 μM) for 72 hours. In the 32-week study, severe retinal vasculopathy was examined by quantitating acellular capillaries and extracellular matrix proteins. In diabetic rats, FT011 reduced retinal leukostasis, microglial density and mRNA levels of intercellular adhesion molecule-1 (ICAM-1). In Müller cells, FT011 reduced diabetes-induced gliosis and vascular endothelial growth factor (VEGF) immunolabeling and the hyperglycaemic-induced increase in ICAM-1, monocyte chemoattractant protein-1, CCL20, cytokine-induced neutrophil chemoattractant-1, VEGF and IL-6. Late intervention with FT011 reduced acellular capillaries and the elevated mRNA levels of collagen IV and fibronectin in diabetic rats. In conclusion, the protective effects of FT011 in cardiorenal disease extend to key elements of diabetic retinopathy and

  19. Characterisation of human non-proliferative diabetic retinopathy using the fractal analysis

    PubMed Central

    Ţălu, Ştefan; Călugăru, Dan Mihai; Lupaşcu, Carmen Alina

    2015-01-01

    AIM To investigate and quantify changes in the branching patterns of the retina vascular network in diabetes using the fractal analysis method. METHODS This was a clinic-based prospective study of 172 participants managed at the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and December 2013. A set of 172 segmented and skeletonized human retinal images, corresponding to both normal (24 images) and pathological (148 images) states of the retina were examined. An automatic unsupervised method for retinal vessel segmentation was applied before fractal analysis. The fractal analyses of the retinal digital images were performed using the fractal analysis software ImageJ. Statistical analyses were performed for these groups using Microsoft Office Excel 2003 and GraphPad InStat software. RESULTS It was found that subtle changes in the vascular network geometry of the human retina are influenced by diabetic retinopathy (DR) and can be estimated using the fractal geometry. The average of fractal dimensions D for the normal images (segmented and skeletonized versions) is slightly lower than the corresponding values of mild non-proliferative DR (NPDR) images (segmented and skeletonized versions). The average of fractal dimensions D for the normal images (segmented and skeletonized versions) is higher than the corresponding values of moderate NPDR images (segmented and skeletonized versions). The lowest values were found for the corresponding values of severe NPDR images (segmented and skeletonized versions). CONCLUSION The fractal analysis of fundus photographs may be used for a more complete undeTrstanding of the early and basic pathophysiological mechanisms of diabetes. The architecture of the retinal microvasculature in diabetes can be quantitative quantified by means of the fractal dimension. Microvascular abnormalities on retinal imaging may elucidate early mechanistic pathways for microvascular complications and distinguish patients with DR from

  20. Characterization of cells from patient-derived fibrovascular membranes in proliferative diabetic retinopathy

    PubMed Central

    Kim, Leo A.; Wong, Lindsay L.; Amarnani, Dhanesh S.; Bigger-Allen, Alexander A.; Hu, Yang; Marko, Christina K.; Eliott, Dean; Shah, Vinay A.; McGuone, Declan; Stemmer-Rachamimov, Anat O.; Gai, Xiaowu; D’Amore, Patricia A.

    2015-01-01

    Purpose Epiretinal fibrovascular membranes (FVMs) are a hallmark of proliferative diabetic retinopathy (PDR). Surgical removal of FVMs is often indicated to treat tractional retinal detachment. This potentially informative pathological tissue is usually disposed of after surgery without further examination. We developed a method for isolating and characterizing cells derived from FVMs and correlated their expression of specific markers in culture with that in tissue. Methods FVMs were obtained from 11 patients with PDR during diabetic vitrectomy surgery and were analyzed with electron microscopy (EM), comparative genomic hybridization (CGH), immunohistochemistry, and/or digested with collagenase II for cell isolation and culture. Antibody arrays and enzyme-linked immunosorbent assay (ELISA) were used to profile secreted angiogenesis-related proteins in cell culture supernatants. Results EM analysis of the FVMs showed abnormal vessels composed of endothelial cells with large nuclei and plasma membrane infoldings, loosely attached perivascular cells, and stromal cells. The cellular constituents of the FVMs lacked major chromosomal aberrations as shown with CGH. Cells derived from FVMs (C-FVMs) could be isolated and maintained in culture. The C-FVMs retained the expression of markers of cell identity in primary culture, which define specific cell populations including CD31-positive, alpha-smooth muscle actin-positive (SMA), and glial fibrillary acidic protein-positive (GFAP) cells. In primary culture, secretion of angiopoietin-1 and thrombospondin-1 was significantly decreased in culture conditions that resemble a diabetic environment in SMA-positive C-FVMs compared to human retinal pericytes derived from a non-diabetic donor. Conclusions C-FVMs obtained from individuals with PDR can be isolated, cultured, and profiled in vitro and may constitute a unique resource for the discovery of cell signaling mechanisms underlying PDR that extends beyond current animal and cell

  1. Quantitative computerized color vision testing in diabetic retinopathy: A possible screening tool?

    PubMed Central

    Al Saeidi, Rashid; Kernt, Marcus; Kreutzer, Thomas C; Rudolph, Guenther; Neubauer, Aljoscha S; Haritoglou, Christos

    2013-01-01

    Purpose: To evaluate the efficacy of a computerized color vision testing (Arden color contrast test) as a screening test for detection of diabetic macular edema (DME). Materials and Methods: A consecutive, prospective case series of 83 eyes of 42 diabetic patients with and without macular edema was enrolled. Macular edema was assessed clinically by stereoscopic grading and by central retinal thickness measurement with optical coherence tomography (OCT). Additionally, a computerized chromatest for the protan- and tritan-axis was performed. Analysis of test characteristics included receiver operating characteristic (ROC) curves and calculated sensitivity and specificity. Results: Sixty-one eyes had clinically significant macular edema (CSME). OCT yielded an area under the ROC curve (AUC) of 0.92. Color vision testing yielded an AUC of 0.82 for the tritan- and 0.80 for the protan-axis. Using a cut off of 199 microns OCT resulted in a 100% sensitivity at 39% specificity. With a cut-off of 4.85, color testing yielded a sensitivity of 100% at a specificity of 8% on the tritan-axis, respectively. Considering OCT instead of clinical examination as a reference standard resulted in a comparable high sensitivity, but low specificity for color vision testing. Disturbance of the tritan axis was more pronounced than for the protan axis in present macular edema and also better correlated (r = 0.46) with retinal thickness measured with OCT. Conclusions: Computerized, quantitative color testing using the chromatest allows detection of diabetic maculopathy with high sensitivity. However, only a low specificity exists for retinal macular edema, as in diabetic retinopathy (DR) frequently abnormalities of the tritan axis exist before any retinal thickening occurs. PMID:24391371

  2. The Effects of Diabetic Retinopathy and Pan-Retinal Photocoagulation on Photoreceptor Cell Function as Assessed by Dark Adaptometry

    PubMed Central

    Bavinger, J. Clay; Dunbar, Grace E.; Stem, Maxwell S.; Blachley, Taylor S.; Kwark, Leon; Farsiu, Sina; Jackson, Gregory R.; Gardner, Thomas W.

    2016-01-01

    Purpose The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. Methods Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5° superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral-domain optical coherence tomography (OCT). Results The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. Conclusions The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR. PMID:26803796

  3. Evaluation of Intravitreal Ranibizumab on the Surgical Outcome for Diabetic Retinopathy With Tractional Retinal Detachment.

    PubMed

    Dong, Feng; Yu, Chenying; Ding, Haiyuan; Shen, Liping; Lou, Dinghua

    2016-02-01

    This study aims to investigate intravitreal injection of Ranibizumab on the surgical outcome for diabetic patients who had tractional retinal detachment but did not receive any preoperative retinal photocoagulation.Ninety-seven patients (97 eyes) who had diabetic retinopathy with tractional retinal detachment were enrolled to receive 23-G pars plana vitrectomy (PPV). They were assigned to an experimental group (Group I, n = 47 eyes) and a control group (Group II, n = 50 eyes). The patients in Group I were given 1 injection of intravitreal Ranibizumab (Lucentis 0.5 mg/0.05 mL) 1 week before surgery, whereas those in Group II went down to surgery directly. Follow-ups were performed for 6 months to 3 years (16 ± 6 months), and indicators observed included postoperative best-corrected visual acuity, complications, and retinal thickness in the macula measured by optical coherence tomography.In Group I, BCVA improved from logMAR 1.92 ± 0.49 to logMAR 0.81 ± 0.39 following surgery, whereas in Group II, BCVA improved from logMAR 1.91 ± 0.49 to logMAR 0.85 ± 0.41. There was significant postoperative gain in vision, but there was no significant difference between the 2 groups at postoperative follow-up visits. The mean duration of vitrectomy in Group I and Group II was (40 ± 7) minutes and (53 ± 9) minutes, respectively, with significant difference. Iatrogenic breaks were noted in 5 eyes (11%) in the experimental group and 17 eyes (34%) in the control group; the difference was significant. The retinal thickness in the macula measured by OCT was (256 ± 44) μm and (299 ± 84) μm in Group I and Group II respectively with significant difference. Besides, there were significantly more eyes in Group II that required silicone oil tamponade and postoperative retinal photocoagulation.23-G PPV combined with intravitreal tamponade and panretinal photocoagulation still remains an effective regimen for the treatment of

  4. Results of Automated Retinal Image Analysis for Detection of Diabetic Retinopathy from the Nakuru Study, Kenya

    PubMed Central

    2015-01-01

    Objective Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It has been established that currently about 1% of the world’s blind or visually impaired is due to DR. However, the increasing prevalence of diabetes mellitus and DR is creating an increased workload on those with expertise in grading retinal images. Safe and reliable automated analysis of retinal images may support screening services worldwide. This study aimed to compare the Iowa Detection Program (IDP) ability to detect diabetic eye diseases (DED) to human grading carried out at Moorfields Reading Centre on the population of Nakuru Study from Kenya. Participants Retinal images were taken from participants of the Nakuru Eye Disease Study in Kenya in 2007/08 (n = 4,381 participants [NW6 Topcon Digital Retinal Camera]). Methods First, human grading was performed for the presence or absence of DR, and for those with DR this was sub-divided in to referable or non-referable DR. The automated IDP software was deployed to identify those with DR and also to categorize the severity of DR. Main Outcome Measures The primary outcomes were sensitivity, specificity, and positive and negative predictive value of IDP versus the human grader as reference standard. Results Altogether 3,460 participants were included. 113 had DED, giving a prevalence of 3.3% (95% CI, 2.7–3.9%). Sensitivity of the IDP to detect DED as by the human grading was 91.0% (95% CI, 88.0–93.4%). The IDP ability to detect DED gave an AUC of 0.878 (95% CI 0.850–0.905). It showed a negative predictive value of 98%. The IDP missed no vision threatening retinopathy in any patients and none of the false negative cases met criteria for treatment. Conclusions In this epidemiological sample, the IDP’s grading was comparable to that of human graders’. It therefore might be feasible to consider inclusion into usual epidemiological grading. PMID:26425849

  5. Evaluation of Intravitreal Ranibizumab on the Surgical Outcome for Diabetic Retinopathy With Tractional Retinal Detachment

    PubMed Central

    Dong, Feng; Yu, Chenying; Ding, Haiyuan; Shen, Liping; Lou, Dinghua

    2016-01-01

    Abstract This study aims to investigate intravitreal injection of Ranibizumab on the surgical outcome for diabetic patients who had tractional retinal detachment but did not receive any preoperative retinal photocoagulation. Ninety-seven patients (97 eyes) who had diabetic retinopathy with tractional retinal detachment were enrolled to receive 23-G pars plana vitrectomy (PPV). They were assigned to an experimental group (Group I, n = 47 eyes) and a control group (Group II, n = 50 eyes). The patients in Group I were given 1 injection of intravitreal Ranibizumab (Lucentis 0.5 mg/0.05 mL) 1 week before surgery, whereas those in Group II went down to surgery directly. Follow-ups were performed for 6 months to 3 years (16 ± 6 months), and indicators observed included postoperative best-corrected visual acuity, complications, and retinal thickness in the macula measured by optical coherence tomography. In Group I, BCVA improved from logMAR 1.92 ± 0.49 to logMAR 0.81 ± 0.39 following surgery, whereas in Group II, BCVA improved from logMAR 1.91 ± 0.49 to logMAR 0.85 ± 0.41. There was significant postoperative gain in vision, but there was no significant difference between the 2 groups at postoperative follow-up visits. The mean duration of vitrectomy in Group I and Group II was (40 ± 7) minutes and (53 ± 9) minutes, respectively, with significant difference. Iatrogenic breaks were noted in 5 eyes (11%) in the experimental group and 17 eyes (34%) in the control group; the difference was significant. The retinal thickness in the macula measured by OCT was (256 ± 44) μm and (299 ± 84) μm in Group I and Group II respectively with significant difference. Besides, there were significantly more eyes in Group II that required silicone oil tamponade and postoperative retinal photocoagulation. 23-G PPV combined with intravitreal tamponade and panretinal photocoagulation still remains an effective regimen for the

  6. Microglia/Macrophages Migrate through Retinal Epithelium Barrier by a Transcellular Route in Diabetic Retinopathy

    PubMed Central

    Omri, Samy; Behar-Cohen, Francine; de Kozak, Yvonne; Sennlaub, Florian; Mafra Verissimo, Lourena; Jonet, Laurent; Savoldelli, Michèle; Omri, Boubaker; Crisanti, Patricia

    2011-01-01

    Diabetic retinopathy is associated with ocular inflammation, leading to retinal barrier breakdown, macular edema, and visual cell loss. We investigated the molecular mechanisms involved in microglia/macrophages trafficking in the retina and the role of protein kinase Cζ (PKCζ) in this process. Goto Kakizaki (GK) rats, a model for spontaneous type 2 diabetes were studied until 12 months of hyperglycemia. Up to 5 months, sparse microglia/macrophages were detected in the subretinal space, together with numerous pores in retinal pigment epithelial (RPE) cells, allowing inflammatory cell traffic between the retina and choroid. Intercellular adhesion molecule–1 (ICAM-1), caveolin-1 (CAV-1), and PKCζ were identified at the pore border. At 12 months of hyperglycemia, the significant reduction of pores density in RPE cell layer was associated with microglia/macrophages accumulation in the subretinal space together with vacuolization of RPE cells and disorganization of photoreceptors outer segments. The intraocular injection of a PKCζ inhibitor at 12 months reduced iNOS expression in microglia/macrophages and inhibited their migration through the retina, preventing their subretinal accumulation. We show here that a physiological transcellular pathway takes place through RPE cells and contributes to microglia/macrophages retinal trafficking. Chronic hyperglycemia causes alteration of this pathway and subsequent subretinal accumulation of activated microglia/macrophages. PMID:21712024

  7. Cost-Utility Analysis of Screening Strategies for Diabetic Retinopathy in Korea

    PubMed Central

    2015-01-01

    This study involved a cost-utility analysis of early diagnosis and treatment of diabetic retinopathy depending on the screening strategy used. The four screening strategies evaluated were no screening, opportunistic examination, systematic fundus photography, and systematic examination by an ophthalmologists. Each strategy was evaluated in 10,000 adults aged 40 yr with newly diagnosed diabetes mellitus (hypothetical cohort). The cost of each strategy was estimated in the perspective of both payer and health care system. The utility was estimated using quality-adjusted life years (QALY). Incremental Cost Effectiveness Ratio (ICER) for the different screening strategies was analyzed. After exclusion of the weakly dominating opportunistic strategy, the ICER of systematic photography was 57,716,867 and that of systematic examination by ophthalmologists was 419,989,046 from the perspective of the healthcare system. According to the results, the systematic strategy is preferable to the opportunistic strategy from the perspective of both a payer and a healthcare system. Although systematic examination by ophthalmologists may have higher utility than systematic photography, it is associated with higher cost. The systematic photography is the best strategy in terms of cost-utility. However systematic examination by ophthalmologists can also be a suitable policy alternative, if the incremental cost is socially acceptable. PMID:26713046

  8. Angiopoietin 2 induces pericyte apoptosis via α3β1 integrin signaling in diabetic retinopathy.

    PubMed

    Park, Sung Wook; Yun, Jang-Hyuk; Kim, Jin Hyoung; Kim, Kyu-Won; Cho, Chung-Hyun; Kim, Jeong Hun

    2014-09-01

    Pericyte loss is an early characteristic change in diabetic retinopathy (DR). Despite accumulating evidence that hyperglycemia-induced angiopoietin 2 (Ang2) has a central role in pericyte loss, the precise molecular mechanism has not been elucidated. This study investigated the role of Ang2 in pericyte loss in DR. We demonstrated that pericyte loss occurred with Ang2 increase in the diabetic mouse retina and that the source of Ang2 could be the endothelial cell. Ang2 induced pericyte apoptosis via the p53 pathway under high glucose, whereas Ang2 alone did not induce apoptosis. Integrin, not Tie-2 receptor, was involved for Ang2-induced pericyte apoptosis under high glucose as an Ang2 receptor. High glucose changed the integrin expression pattern, which increased integrin α3 and β1 in the pericyte. Furthermore, Ang2-induced pericyte apoptosis in vitro was effectively attenuated via p53 suppression by blocking integrin α3 and β1. Although intravitreal injection of Ang2 induced pericyte loss in C57BL/6J mice retina in vivo, intravitreal injection of anti-integrin α3 and β1 antibodies attenuated Ang2-induced pericyte loss. Taken together, Ang2 induced pericyte apoptosis under high glucose via α3β1 integrin. Glycemic control or blocking Ang2/integrin signaling could be a potential therapeutic target to prevent pericyte loss in early DR. PMID:24722242

  9. Current nanotechnology approaches for the treatment and management of diabetic retinopathy.

    PubMed

    Fangueiro, Joana F; Silva, Amélia M; Garcia, Maria L; Souto, Eliana B

    2015-09-01

    Diabetic retinopathy (DR) is a consequence of diabetes mellitus at the ocular level, leading to vision loss, and contributing to the decrease of patient's life quality. The biochemical and anatomic abnormalities that occur in DR are discussed in this review to better understand and manage the development of new therapeutic strategies. The use of new drug delivery systems based on nanoparticles (e.g. liposomes, dendrimers, cationic nanoemulsions, lipid and polymeric nanoparticles) is discussed along with the current traditional treatments, pointing out the advantages of the proposed nanomedicines to target this ocular disease. Despite the multifactorial nature of DR, which is not entirely understood, some strategies based on nanoparticles are being exploited for a more efficient drug delivery to the posterior segment of the eye. On the other hand, the use of some nanoparticles also seems to contribute to the development of DR symptoms (e.g. retinal neovascularization), which are also discussed in light of an efficient management of this ocular chronic disease. PMID:25536109

  10. Cost-Utility Analysis of Screening Strategies for Diabetic Retinopathy in Korea.

    PubMed

    Kim, Sang-Won; Kang, Gil-Won

    2015-12-01

    This study involved a cost-utility analysis of early diagnosis and treatment of diabetic retinopathy depending on the screening strategy used. The four screening strategies evaluated were no screening, opportunistic examination, systematic fundus photography, and systematic examination by an ophthalmologists. Each strategy was evaluated in 10,000 adults aged 40 yr with newly diagnosed diabetes mellitus (hypothetical cohort). The cost of each strategy was estimated in the perspective of both payer and health care system. The utility was estimated using quality-adjusted life years (QALY). Incremental Cost Effectiveness Ratio (ICER) for the different screening strategies was analyzed. After exclusion of the weakly dominating opportunistic strategy, the ICER of systematic photography was 57,716,867 and that of systematic examination by ophthalmologists was 419,989,046 from the perspective of the healthcare system. According to the results, the systematic strategy is preferable to the opportunistic strategy from the perspective of both a payer and a healthcare system. Although systematic examination by ophthalmologists may have higher utility than systematic photography, it is associated with higher cost. The systematic photography is the best strategy in terms of cost-utility. However systematic examination by ophthalmologists can also be a suitable policy alternative, if the incremental cost is socially acceptable. PMID:26713046

  11. Novel approaches for treating diabetic retinopathy based on recent pathogenic evidence.

    PubMed

    Simó, Rafael; Hernández, Cristina

    2015-09-01

    Diabetic retinopathy remains as a leading cause of blindness in developed countries. Current treatments target late stages of DR when vision has already been significantly affected. A better understanding of the pathogenesis of DR would permit the development of more efficient preventional/interventional strategies against early stages of DR. In this article a critical review of the state of the art of this issue is provided along with a discussion of problems which have yet to be overcome. Neuroprotection as a new approach for the treatment of the early stages of DR has been particularly emphasized. The development and progression of DR is not homogeneous and, apart from blood glucose levels and blood pressure, it depends on genetic factors which remain to be elucidated. In addition, the role of the pathogenic pathways is not the same in all patients. All these factors should be taken into account in the near future when an individualized oriented treatment for DR could become feasible. The new techniques in retinal imaging acquisition, the identification of useful circulating biomarkers and the individualized analysis of biological samples could facilitate the development of early and personalized therapy in the setting of DR. Finally, it should be noted that only a coordinated action among ophthalmologists, diabetologists, basic researchers, experts in pharmaco-economics and health care providers addressed to the design of rational strategies targeting prevention and the early stages of DR will be effective in reducing the burden and improving the clinical outcome of this devastating complication of diabetes. PMID:25936649

  12. Choosing preclinical study models of diabetic retinopathy: key problems for consideration

    PubMed Central

    Mi, Xue-Song; Yuan, Ti-Fei; Ding, Yong; Zhong, Jing-Xiang; So, Kwok-Fai

    2014-01-01

    Diabetic retinopathy (DR) is the most common complication of diabetes mellitus in the eye. Although the clinical treatment for DR has already developed to a relative high level, there are still many urgent problems that need to be investigated in clinical and basic science. Currently, many in vivo animal models and in vitro culture systems have been applied to solve these problems. Many approaches have also been used to establish different DR models. However, till now, there has not been a single study model that can clearly and exactly mimic the developmental process of the human DR. Choosing the suitable model is important, not only for achieving our research goals smoothly, but also, to better match with different experimental proposals in the study. In this review, key problems for consideration in choosing study models of DR are discussed. These problems relate to clinical relevance, different approaches for establishing models, and choice of different species of animals as well as of the specific in vitro culture systems. Attending to these considerations will deepen the understanding on current study models and optimize the experimental design for the final goal of preventing DR. PMID:25429204

  13. Vitrectomy for Proliferative Diabetic Retinopathy in a Patient with Heparin-Induced Thrombocytopenia

    PubMed Central

    Fujii, Tomoko; Akashi, Mari; Morishita, Seita; Fukumoto, Masanori; Suzuki, Hiroyuki; Kobayashi, Takatoshi; Kida, Teruyo; Kagitani, Maki; Morino, Ichiro; Ikeda, Tsunehiko

    2016-01-01

    Introduction In this study, we report a case of proliferative diabetic retinopathy in a patient with heparin-induced thrombocytopenia (HIT) in whom vitrectomy was performed with good results. Case A 57-year-old man presented with a chief complaint of decreased visual acuity (VA) in the left eye. Corrected VA of the left eye was 0.03, and ophthalmic examination showed fibrovascular membranes along the vascular arcade and a combined rhegmatogenous-traction retinal detachment with a macular hole. The patient began hemodialysis for diabetic nephropathy in March 2014; thrombocytopenia developed after dialysis was started, and HIT was diagnosed after further evaluation. Argatroban hydrate was being used during dialysis. Treatment was switched from warfarin to argatroban hydrate 6 days prior to vitrectomy being performed on the patient's left eye. Although there was bleeding with somewhat difficult hemostasis during the intraoperative treatment of the fibrovascular membranes, surgery was completed without complications and the postoperative course was good. Discussion Vitrectomy was performed with good results in this patient with HIT. Treatment with argatroban hydrate during surgery enabled surgery without the danger of intraoperative clotting. PMID:26933432

  14. Detection and classification of retinal lesions for grading of diabetic retinopathy.

    PubMed

    Usman Akram, M; Khalid, Shehzad; Tariq, Anam; Khan, Shoab A; Azam, Farooque

    2014-02-01

    Diabetic Retinopathy (DR) is an eye abnormality in which the human retina is affected due to an increasing amount of insulin in blood. The early detection and diagnosis of DR is vital to save the vision of diabetes patients. The early signs of DR which appear on the surface of the retina are microaneurysms, haemorrhages, and exudates. In this paper, we propose a system consisting of a novel hybrid classifier for the detection of retinal lesions. The proposed system consists of preprocessing, extraction of candidate lesions, feature set formulation, and classification. In preprocessing, the system eliminates background pixels and extracts the blood vessels and optic disc from the digital retinal image. The candidate lesion detection phase extracts, using filter banks, all regions which may possibly have any type of lesion. A feature set based on different descriptors, such as shape, intensity, and statistics, is formulated for each possible candidate region: this further helps in classifying that region. This paper presents an extension of the m-Mediods based modeling approach, and combines it with a Gaussian Mixture Model in an ensemble to form a hybrid classifier to improve the accuracy of the classification. The proposed system is assessed using standard fundus image databases with the help of performance parameters, such as, sensitivity, specificity, accuracy, and the Receiver Operating Characteristics curves for statistical analysis. PMID:24480176

  15. New Therapeutic Window of Regenerative Opportunity in Diabetic Retinopathy by VESGEN Analysis

    NASA Technical Reports Server (NTRS)

    Parsons-Wingert, Patricia A.

    2012-01-01

    Vascular pattern may serve as a useful new biomarker principle of complex, multi-scale signaling in pathological, physiological angiogenesis and microvascular remodeling. Each angiogenesis stimulator or inhibitor we have analyzed, including VEGF, bFGF, TGF-beta1, angiostatin and triamcinolone acetonide, has induced a novel "fingerprint" or "signature" biomarker vascular pattern that is spatio-temporally unique. Remodeling vasculature thereby provides an informative read-out of dominant molecular signaling, when analyzed by innovative, fractal-based VESsel GENeration (VESGEN) Analysis software. Using VESGEN to analyze ophthalmic clinical vascular images, we recently introduced a potential paradigm shift to the understanding of early-stage progression that suggests new regenerative opportunities for human diabetic retinopathy (DR), the major blinding disease for working-aged adults. In a pilot study, we discovered that angiogenesis oscillates as a surprising, homeostatic-like regeneration of retinal vessels during early progression of DR (IOVS 51(1):498). Results suggest that the term non-proliferative DR may be a misnomer. In new studies, normalization of the vasculature will be determined from the response of vascular pattern to therapeutic monitoring and treatment. We have mapped and quantified in vivo experimental models of angiogenesis, lymphangiogenesis and intravital blood flow from cellular/molecular to higher systems levels that include a murine model of infant retinopathy of prematurity (ROP); developing and pathological coronary and placental-like vessel models; progressive intestinal inflammation, growing murine tumors, and other pathological, physiological and therapeutically treated tissues of transgenic mice and avian embryos. Vascular Alterations, Visual Impairments (VIIP) & Increased Intracranial Pressure (ICP), Immunosuppression & Bone Loss: NASA-defined risk categories for human space exploration and ISS Utilization

  16. Regular Chinese Green Tea Consumption Is Protective for Diabetic Retinopathy: A Clinic-Based Case-Control Study

    PubMed Central

    Ma, Qinghua; Chen, Dandan; Sun, Hong-Peng; Yan, Ning; Xu, Yong; Pan, Chen-Wei

    2015-01-01

    Objective. To determine the association between regular Chinese green tea consumption and the risk of diabetic retinopathy (DR) in diabetic patients in China. Methods. 100 DR patients and 100 age-sex-matched diabetic controls without retinopathy were recruited in a clinic-based, case-control study. DR was defined from retinal photographs and detailed information on Chinese green tea consumption of the participants was collected through a face-to-face interview. Results. The crude odds ratio [OR] of Chinese green tea consumption for DR was 0.49 (95% confidence interval: 0.26–0.90). When stratified by sex, the protective effect of Chinese green tea consumption on DR was statistically significant in women (P = 0.01) but not in men (P = 0.63). After adjusting for age, sex, and other confounders, DR was significantly associated with Chinese green tea consumption (OR = 0.48; P = 0.04), higher systolic blood pressure (OR = 1.02; P = 0.05), longer duration of diabetes (OR = 1.07; P = 0.02), and the presence of family history of diabetes (OR = 2.35; P = 0.04). Conclusions. Diabetic patients who had regularly drunk Chinese green tea every week for at least one year in their lives had a DR risk reduction of about 50% compared with those who had not. Regular Chinese green tea consumption may be a novel approach for the prevention of DR. PMID:26539551

  17. Automatic Analysis of Retinal Vascular Parameters for Detection of Diabetes in Indian Patients with No Retinopathy Sign.

    PubMed

    Aliahmad, Behzad; Kumar, Dinesh Kant; Jain, Rajeev

    2016-01-01

    This study has investigated the association between retinal vascular parameters with type II diabetes in Indian population with no observable diabetic retinopathy. It has introduced two new retinal vascular parameters: total number of branching angles (TBA) and average acute branching angles (ABA) as potential biomarkers of diabetes in an explanatory model. A total number of 180 retinal images (two (left and right) × two (ODC and MC) × 45 subjects (13 diabetics and 32 nondiabetics)) were analysed. Stepwise linear regression analysis was performed to model the association between type II diabetes with the best subset of explanatory variables (predictors), consisting of retinal vascular parameters and patients' demographic information. P value of the estimated coefficients (P < 0.001) indicated that, at α level of 0.05, the newly introduced retinal vascular parameters, that is, TBA and ABA together with CRAE, mean tortuosity, SD of branching angle, and VB, are related to type II diabetes when there is no observable sign of retinopathy. PMID:27579347

  18. Automatic Analysis of Retinal Vascular Parameters for Detection of Diabetes in Indian Patients with No Retinopathy Sign

    PubMed Central

    Jain, Rajeev

    2016-01-01

    This study has investigated the association between retinal vascular parameters with type II diabetes in Indian population with no observable diabetic retinopathy. It has introduced two new retinal vascular parameters: total number of branching angles (TBA) and average acute branching angles (ABA) as potential biomarkers of diabetes in an explanatory model. A total number of 180 retinal images (two (left and right) × two (ODC and MC) × 45 subjects (13 diabetics and 32 nondiabetics)) were analysed. Stepwise linear regression analysis was performed to model the association between type II diabetes with the best subset of explanatory variables (predictors), consisting of retinal vascular parameters and patients' demographic information. P value of the estimated coefficients (P < 0.001) indicated that, at α level of 0.05, the newly introduced retinal vascular parameters, that is, TBA and ABA together with CRAE, mean tortuosity, SD of branching angle, and VB, are related to type II diabetes when there is no observable sign of retinopathy. PMID:27579347

  19. The Potential Association between Obstructive Sleep Apnea and Diabetic Retinopathy in Severe Obesity—The Role of Hypoxemia

    PubMed Central

    Banerjee, Dev; Leong, Wen Bun; Arora, Teresa; Nolen, Melissa; Punamiya, Vikas; Grunstein, Ron; Taheri, Shahrad

    2013-01-01

    Background Obstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications. Methods To investigate the association between OSA, hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m2) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA−). Results Forty-six patients were OSA+: median (95% CI) AHI = 37(23–74)/hour and 47 were OSA–ve (AHI = 7(4–11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA− groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65–0.95; p<0.05), after adjustment. Conclusions The presence of OSA, as determined by AHI, was not associated with diabetic retinal complications. In contrast, severity of hypoxemia during sleep (minimum oxygen saturations) may be an important factor. The importance of hypoxia in the development of retinal complications in patients with OSA remains unclear and further studies assessing the pathogenesis of hypoxemia in patients with OSA and diabetic retinal disease are warranted. PMID:24260240

  20. Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes

    PubMed Central

    Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

    2016-01-01

    Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = −0.52, P value = 0.003] and retinal ischemia [beta-coefficient = −0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = −0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR. PMID:27200379

  1. Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes.

    PubMed

    Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

    2016-01-01

    Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = -0.52, P value = 0.003] and retinal ischemia [beta-coefficient = -0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = -0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR. PMID:27200379

  2. Oxidants, antioxidants and mitochondrial function in non-proliferative diabetic retinopathy

    PubMed Central

    Rodríguez-Carrizalez, Adolfo Daniel; Castellanos-González, José Alberto; Martínez-Romero, Esaú César; Miller-Arrevillaga, Guillermo; Villa-Hernández, David; Hernández-Godínez, Pedro Pablo; Ortiz, Genaro Gabriel; Pacheco-Moisés, Fermín Paul; Cardona-Muñoz, Ernesto Germán; Miranda-Díaz, Alejandra Guillermina

    2014-01-01

    Background Diabetic retinopathy (DR) is a preventable cause of visual disability. The aims of the present study were to investigate levels and behavior oxidative stress markers and mitochondrial function in non-proliferative DR (NPDR) and to establish the correlation between the severity of NPDR and markers of oxidative stress and mitochondrial function. Methods In a transverse analysis, type 2 diabetes mellitus (T2DM) patients with mild, moderate and severe non-proliferative DR (NPDR) were evaluated for markers of oxidative stress (i.e. products of lipid peroxidation (LPO) and nitric oxide (NO) catabolites) and antioxidant activity (i.e. total antioxidant capacity (TAC), catalase, and glutathione peroxidase (GPx) activity of erythrocytes). Mitochondrial function was also determined as the fluidity of the submitochondrial particles of platelets and the hydrolytic activity of F0/F1-ATPase. Results Levels of LPO and NO were significantly increased in T2DM patients with severe NPDR (3.19 ± 0.05 μmol/mL and 45.62 ± 1.27 pmol/mL, respectively; P < 0.007 and P < 0.0001 vs levels in health volunteers, respectively), suggesting the presence of oxidative stress. TAC had significant decrease levels with minimum peak in severe retinopathy with 7.98 ± 0.48 mEq/mL (P < 0.0001). In contrast with TAC, erythrocyte catalase and GPx activity was increased in patients with severe NPDR (139.4 ± 4.4 and 117.13 ± 14.84 U/mg, respectively; P < 0.0001 vs healthy volunteers for both), suggesting an imbalance between oxidants and antioxidants. The fluidity of membrane submitochondrial particles decreased significantly in T2DM patients with mild, moderate, or severe NPDR compared with that in healthy volunteers (P < 0.0001 for all). Furthermore, there was a significant increase in the hydrolytic activity of the F0/F1-ATPase in T2DM patients with mild NPDR (265.07 ± 29.55 nmol/PO4; P < 0.0001 vs healthy volunteers), suggesting

  3. Vascular Endothelial Growth Factor Gene Polymorphism is not Associated with Diabetic Retinopathy in Egyptian Patients

    PubMed Central

    Abdel Fattah, Rana Ahmed; Eltanamly, Rasha Mounir; Nabih, Mostafa Hamed; Kamal, Manal Mohammed

    2016-01-01

    Purpose: Vascular endothelial growth factor (VEGF) was implicated as a major contributor to the development of diabetic retinopathy (DR). This study investigated whether single nucleotide polymorphisms of A allele of rs699947 or G allele of rs10434 in the VEGF gene were associated with DR in Egyptian patients with type 2 diabetes mellitus (DM). Methods: This is a case–controlled study which was performed at Cairo University Hospital in 2012 on Egyptian patients with type 2 DM with and without DR. Healthy adults without diabetes comprised the comparison group. Patients underwent an ophthalmological examination and fundus photography. Genotyping was performed for the A allele of rs699947 and the G allele of rs10434 polymorphisms using real-time polymerase chain reaction. Results: A total of 128 patients were enrolled in this study and divided into three groups: Group A included 46 patients with type 2 DM and DR; Group B included 41 patients with type 2 DM without DR; and Group C included 41 healthy controls. There was no significant association between rs699947 or rs10434 and any of the three groups (P = 0.5, P = 0.7, respectively). Allelic frequency in the three groups was not statistically significant for rs699947 or rs10434 (P = 0.6, P = 0.6, respectively). Conclusion: Rs699947 or rs10434 polymorphism was not associated with the presence of DR in Egyptian patients. Further studies are required before genetic testing for polymorphism can be used clinically to correlate with DR. PMID:26957843

  4. Sensitivity and specificity of nonmydriatic digital imaging in screening diabetic retinopathy in Indian eyes

    PubMed Central

    Gupta, Vishali; Bansal, Reema; Gupta, Amod; Bhansali, Anil

    2014-01-01

    Background: Nonmydriatic digital imaging (NMDI) is ideal for screening diabetic retinopathy (DR), but its use in Indian eyes has not been evaluated. Aim: The aim was to evaluate the sensitivity and specificity of NMDI as a screening tool in detecting DR in Indian eyes. Design: A prospective, nonrandomized, noncomparative, noninterventional study. Materials and Methods: A total of 500 diabetic patients visiting the endocrinology clinic (September 2008-June 2010) underwent NMDI (Zeiss Procam), followed by routine dilated fundus photography (FP; Zeiss Visupac 450+) of 345° retinal fields (1) optic disc and macula, (2) superotemporal, and (3) nasal to optic disc. Two-masked retina specialists graded the images for quality and severity of DR, and compared between NMDI and dilated FP. Statistical Analysis: SPSS Windows 17 for version. Results: Mean age was 52.97 ± 13.46 years (306 males: 194 females). The rate of ungradable images was 30.6% and 31% by the two observers. By observer 1, the sensitivity and specificity of detecting any DR was 58.8% and 69.1%, respectively, (κ = 0.608) and sight-threatening DR (STDR) was 63.1% and 68.9%, respectively, (κ = 0.641). By observer 2, the sensitivity and specificity was 57.3% and 68.3%, respectively, for any DR (κ = 0.593) and 62.8% and 68.3%, respectively, for STDR (κ = 0.637). The level of agreement between two observers was high (κ = 0.96). Conclusion: A high rate of poor quality photographs and low sensitivity limited the use of NMDI as a perfect screening system, particularly in dark iris population with diabetes as seen in Indian eyes. PMID:25230960

  5. Protective Effects of Astragaloside IV on db/db Mice with Diabetic Retinopathy

    PubMed Central

    Mao, Pingan; Zhao, Chen; Huang, Qiong; Zhang, Rihua; Fang, Yuan; Song, Qinglu; Yuan, Dongqing; Xie, Ping; Liu, Yun; Liu, Qinghuai

    2014-01-01

    Objectives Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the potential biological functions of astragaloside IV (AS IV) have long been described in traditional system of medicine, its protective effect on DR remains unclear. This study aims to investigate the function and mechanism of AS IV on type 2 diabetic db/db mice. Methods Db/db mice were treated with AS IV (4.5 mg/kg or 9 mg/kg) or physiological saline by oral gavage for 20 weeks along with db/m mice. In each group, retinal ganglion cell (RGC) function was measured by pattern electroretinogram (ERG) and apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Blood and retina aldose reductase (AR) activity were quantified by chemiluminescence analysis. The expressions of phosporylated-ERK1/2, NF-κB were determined by Western blot analysis. Furthermore, the expression of related downstream proteins were quantified by Label-based Mouse Antibody Array. Results Administration of AS IV significantly improved the amplitude in pattern ERG and reduced the apoptosis of RGCs.in db/db mice. Furthermore, downregulation of AR activity, ERK1/2 phosphorylation, NF-κB and related cytokine were observed in AS IV treatment group. Conclusions Our study indicated that AS IV, as an inhibitor of AR, could prevent the activation of ERK1/2 phosporylation and NF-kB and further relieve the RGCs disfunction in db/db mice with DR. It has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing DR. PMID:25411784

  6. Oscillation of Angiogenesis with Vascular Dropout in Diabetic Retinopathy by VESsel GENeration Analysis (VESGEN)

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; Radbakrishnan, Krisbnan; Vickerman, Mary B.; Kaiser, Peter K.

    2010-01-01

    PURPOSE. Vascular dropout and angiogenesis are hallmarks of the progression of diabetic retinopathy (DR). However, current evaluation of DR relies on grading of secondary vascular effects, such as microaneurysms and hemorrhages, by clinical examination instead of by evaluation of actual vascular changes. The purpose of this study was to map and quantify vascular changes during progression of DR by VESsel GENeration Analysis (VESGEN). METHODS. In this prospective cross-sectional study, 15 eyes with DR were evaluated with fluorescein angiography (FA) and color fundus photography, and were graded using modified Early Treatment Diabetic Retinopathy Study criteria. FA images were separated by semiautomatic image processing into arterial and venous trees. Vessel length density (L(sub v)), number density (N(sub v)), and diameter (D(sub v)) were analyzed in a masked fashion with VESGEN software. Each vascular tree was automatically segmented into branching generations (G(sub 1)...G(sub 8) or G(sub 9)) by vessel diameter and branching. Vascular remodeling status (VRS) for N(sub v) and L(sub v) was graded 1 to 4 for increasing severity of vascular change. RESULTS. By N(sub v) and L(sub v), VRS correlated significantly with the independent clinical diagnosis of mild to proliferative DR (13/15 eyes). N(sub v) and L(sub v) of smaller vessels (G(sub >=6) increased from VRS1 to VRS2 by 2.4 X and 1.6 X, decreased from VRS2 to VRS3 by 0.4 X and 0.6X, and increased from VRS3 to VRS4 by 1.7 X and 1.5 X (P < 0.01). Throughout DR progression, the density of larger vessels (G(sub 1-5)) remained essentially unchanged, and D(sub v1-5) increased slightly. CONCLUSIONS. Vessel density oscillated with the progression of DR. Alternating phases of angiogenesis/neovascularization and vascular dropout were dominated first by remodeling of arteries and subsequently by veins.

  7. Biomarkers for Diabetic Retinopathy – Could Endothelin 2 Be Part of the Answer?

    PubMed Central

    Ali Rahman, Ireni S.; Vagaja, Nermina N.; Lai, Chooi-May

    2016-01-01

    Purpose The endothelins are a family of three highly conserved and homologous vasoactive peptides that are expressed across all organ systems. Endothelin (Edn) dysregulation has been implicated in a number of pathophysiologies, including diabetes and diabetes-related complications. Here we examined Edn2 and endothelin receptor B (Endrb) expression in retinae of diabetic mouse models and measured serum Edn2 to assess its biomarker potential. Materials and Methods Edn2 and Ednrb mRNA and Edn2 protein expression were assessed in young (8wk) and mature (24wk) C57Bl/6 (wild type; wt), Kimba (model of retinal neovascularisation, RNV), Akita (Type 1 diabetes; T1D) and Akimba mice (T1D plus RNV) by qRT-PCR and immunohistochemistry. Edn2 protein concentration in serum was measured using ELISA. Results Fold-changes in Edn2 and Ednrb mRNA were seen only in young Kimba (Edn2: 5.3; Ednrb: 6.0) and young Akimba (Edn2: 7.9, Ednrb: 8.8) and in mature Kimba (Edn2:9.2, Ednrb:11.2) and mature Akimba (Edn2:14.0, Ednrb:17.5) mice. Co-localisation of Edn2 with Müller-cell-specific glutamine synthetase demonstrated Müller cells and photoreceptors as the major cell types for Edn2 expression in all animal models. Edn2 serum concentrations in young Kimba, Akita and Akimba mice were not elevated compared to wt. However, in mature mice, Edn2 serum concentration was increased in Akimba (6.9pg/mg total serum protein) compared to wt, Kimba and Akita mice (3.9, 4.6, and 3.8pg/mg total serum protein, respectively; p<0.05). Conclusions These results demonstrated that long-term hyperglycaemia in conjunction with VEGF-driven RNV increased Edn2 serum concentration suggesting Edn2 might be a candidate biomarker for vascular changes in diabetic retinopathy. PMID:27482904

  8. Strategies to Screen for Diabetic Retinopathy in Chinese Patients with Newly Diagnosed Type 2 Diabetes: A Cost-Effectiveness Analysis.

    PubMed

    Wu, Bin; Li, Jin; Wu, Haixiang

    2015-11-01

    To investigate the cost-effectiveness of different screening intervals for diabetic retinopathy (DR) in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Chinese healthcare system.Chinese general clinical setting. A cost-effectiveness model was developed to simulate the disease course of Chinese population with newly diagnosed with diabetes. Different DR screening programs were modeled to project economic outcomes. To develop the economic model, we calibrated the progression rates of DR that fit Chinese epidemiologic data derived from the published literature. Costs were estimated from the perspective of the Chinese healthcare system, and the analysis was run over a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. Total costs, vision outcomes, costs per quality-adjusted life year (QALY), the incremental cost-effectiveness ratio (ICER) of screening strategies compared to no screening. DR screening is effective in Chinese patients with newly diagnosed T2DM, and screen strategies with ≥4-year intervals were cost-effective (ICER <$7,485 per QALY) compared to no screening. Screening every 4 years produced the greatest increase in QALYs (11.066) among the cost-effective strategies. The screening intervals could be varied dramatically by age at T2DM diagnosis. Probabilistic sensitivity analyses demonstrated the consistency and robustness of the cost-effectiveness of the 4-year interval screening strategy. The findings suggest that a 4-year interval screening strategy is likely to be more cost-effective than screening every 1 to 3 years in comparison with no screening in the Chinese setting. The screening intervals might be tailored according to the age at T2DM diagnosis. PMID:26559285

  9. Abnormally Low or High Ankle-Brachial Index Is Associated with Proliferative Diabetic Retinopathy in Type 2 Diabetic Mellitus Patients

    PubMed Central

    Chen, Szu-Chia; Hsiao, Pi-Jung; Huang, Jiun-Chi; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yu-Li; Lee, Mei-Yueh; Chang, Jer-Ming; Shin, Shyi–Jang

    2015-01-01

    Although some studies have reported that low ankle-brachial index (ABI) is associated with diabetic retinopathy (DR) in diabetic patients, it remains controversial as to which stage of DR. The aim of this study is to assess whether peripheral artery disease (PAD), indicated by abnormally low or high ABI, is associated with different stages of DR in patients with type 2 diabetes mellitus (DM), and further evaluate the risk factors. A total of 2001 (858 men and 1143 women) patients with type 2 DM who underwent ABI measurement in an outpatient clinic were enrolled. PAD was defined as ABI < 0.9 or ≧ 1.3 in either leg. DR was classified as non-DR, nonproliferative DR and proliferative DR stages. The clinical data were analyzed and the risk factors for abnormal ABI were determined by multivariate logistic regression analysis. The prevalence of ABI < 0.9 or ≧ 1.3 was 3.0%. Multivariate forward logistic regression analysis identified proliferative DR (vs. non-DR) was associated with abnormal ABI (odds ratio, 1.718; 95% confidence interval, 1.152 to 2.562; p = 0.008), but nonproliferative DR was not. Furthermore, the presence of coronary artery disease, cerebrovascular disease, declining renal function and patients without diuretics use were associated with abnormal ABI in patients with proliferative DR. Our study in patients of type 2 DM demonstrated that PAD was associated with proliferative DR. We emphasize the recommendation of performing the ABI test in this population at risk. PMID:26230390

  10. HbA1c Variability as an Independent Risk Factor for Diabetic Retinopathy in Type 1 Diabetes: A German/Austrian Multicenter Analysis on 35,891 Patients

    PubMed Central

    Hermann, Julia M.; Hammes, Hans-Peter; Rami-Merhar, Birgit; Rosenbauer, Joachim; Schütt, Morten; Siegel, Erhard; Holl, Reinhard W.

    2014-01-01

    Objective This study aimed to analyze the effect of HbA1c variability on the occurrence of diabetic retinopathy in type 1 diabetes patients. Patients and Methods 35,891 patients with childhood, adolescent or adult onset of type 1 diabetes from a large multicentre survey, the German/Austrian prospective documentation system (DPV), were analysed. Cox proportional hazard models were used to examine whether intra-individual HbA1c variability expressed as variation coefficient is an independent risk factor for the occurrence of diabetic retinopathy. Results Kaplan-Meier curves stratified by median HbA1c and variation coefficient revealed that retinopathy-free survival probability is lower when both median HbA1c and HbA1c variability are above the 50th percentile. Cox regression models confirmed this finding: After adjustment for age at diabetes onset, gender and median HbA1c, HbA1c variability was independently associated with the occurrence of diabetic retinopathy. Time-covariate interactions used to model non-proportionality indicated an effect decreasing with duration of diabetes for both median HbA1c and HbA1c variability. Predictive accuracy increased significantly when adding HbA1c variability to the Cox regression model. Conclusions In patients with type 1 diabetes, HbA1c variability adds to the risk of diabetic retinopathy independently of average metabolic control. PMID:24609115

  11. Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements

    PubMed Central

    Roig-Revert, María J.; Lleó-Pérez, Antonio; Zanón-Moreno, Vicente; Vivar-Llopis, Bárbara; Marín-Montiel, Juan; Dolz-Marco, Rosa; Alonso-Muñoz, Luis; Albert-Fort, Mara; López-Gálvez, María I.; Galarreta-Mira, David; García-Esparza, María F.; Galbis-Estrada, Carmen; Marco-Ramirez, Carla; Shoaie-Nia, Kian; Sanz-González, Silvia M.; Vila-Bou, Vicente; Bendala-Tufanisco, Elena; García-Medina, José J.; Nucci, Carlo; Gallego-Pinazo, Roberto; Arévalo, J. Fernando; Pinazo-Durán, Maria D.; Valencia Study on Diabetic Retinopathy (VSDR)

    2015-01-01

    We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (−DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (−A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 −DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG−DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation. PMID:26618168

  12. Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements.

    PubMed

    Roig-Revert, María J; Lleó-Pérez, Antonio; Zanón-Moreno, Vicente; Vivar-Llopis, Bárbara; Marín-Montiel, Juan; Dolz-Marco, Rosa; Alonso-Muñoz, Luis; Albert-Fort, Mara; López-Gálvez, María I; Galarreta-Mira, David; García-Esparza, María F; Galbis-Estrada, Carmen; Marco-Ramirez, Carla; Shoaie-Nia, Kian; Sanz-González, Silvia M; Vila-Bou, Vicente; Bendala-Tufanisco, Elena; García-Medina, José J; Nucci, Carlo; Gallego-Pinazo, Roberto; Arévalo, J Fernando; Pinazo-Durán, Maria D; Valencia Study On Diabetic Retinopathy Vsdr

    2015-01-01

    We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation. PMID:26618168

  13. Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy

    PubMed Central

    Dong, Yoko; Dong, Zhenyu; Kase, Satoru; Ando, Ryo; Fukuhara, Junichi; Kinoshita, Satoshi; Inafuku, Saori; Tagawa, Yoshiaki; Ishizuka, Erdal Tan; Saito, Wataru; Murata, Miyuki; Kanda, Atsuhiro; Noda, Kousuke; Ishida, Susumu

    2016-01-01

    AIM To examine phosphorylation of alphaB-crystallin (p-αBC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-αBC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR). METHODS Eleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-αBC, VEGF, CD31, and p-p38 MAPK antibodies. RESULTS Immunoreactivity for p-αBC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-αBC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-αBC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes. CONCLUSION Phosphorylation of αBC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR. PMID:27588262

  14. Ahmed valve implantation for neovascular glaucoma after 23-gauge vitrectomy in eyes with proliferative diabetic retinopathy

    PubMed Central

    Cheng, Yu; Liu, Xiao-Hong; Shen, Xi; Zhong, Yi-Sheng

    2013-01-01

    AIM To report on the outcome of Ahmed glaucoma valve (AGV) implantation for the management of neovascular glaucoma (NVG) after 23-gauge vitrectomy for proliferative diabetic retinopathy (PDR). METHODS Twelve medically uncontrolled NVG with earlier 23-gauge vitrectomy for PDR underwent AGV implantation. The control of intraocular pressure (IOP), preoperative and postoperative best-corrected visual acuity, the development of intraoperative and postoperative complications were evaluated during the follow-up. RESULTS The mean follow-up was 15.4±4.3 months (9-23 months). Mean preoperative IOP was 49.4±5.1mmHg and mean postoperative IOP at the last visit was 17.5±1.6mmHg. The control of IOP was achieved at the final follow-up visits in all patients, however, 8 of 12 patients still needed anti-glaucoma medication (mean number of medications, 0.8±0.7). The visual acuity improved in nine eyes, and the visual acuity unchanged in three eyes at the final follow-up visits. The complications that occurred were minor hyphema in three eyes, choroid detachment in two eyes, and the minor hyphema and choroid detachments were reabsorbed without any surgical intervention. CONCLUSION AGV implantation is a safe and effective procedure that enables successful IOP control and vision preservation in the NVG patients with the history of earlier 23-gauge vitrectomy for PDR. PMID:23826525

  15. Effects of image compression and degradation on an automatic diabetic retinopathy screening algorithm

    NASA Astrophysics Data System (ADS)

    Agurto, C.; Barriga, S.; Murray, V.; Pattichis, M.; Soliz, P.

    2010-03-01

    Diabetic retinopathy (DR) is one of the leading causes of blindness among adult Americans. Automatic methods for detection of the disease have been developed in recent years, most of them addressing the segmentation of bright and red lesions. In this paper we present an automatic DR screening system that does approach the problem through the segmentation of features. The algorithm determines non-diseased retinal images from those with pathology based on textural features obtained using multiscale Amplitude Modulation-Frequency Modulation (AM-FM) decompositions. The decomposition is represented as features that are the inputs to a classifier. The algorithm achieves 0.88 area under the ROC curve (AROC) for a set of 280 images from the MESSIDOR database. The algorithm is then used to analyze the effects of image compression and degradation, which will be present in most actual clinical or screening environments. Results show that the algorithm is insensitive to illumination variations, but high rates of compression and large blurring effects degrade its performance.

  16. A Case of Uveal Colobomas Showing Marked Left-Right Difference in Diabetic Retinopathy

    PubMed Central

    Moriya, Takeshi; Ochi, Ryosuke; Imagawa, Yukihiro; Sato, Bumpei; Morishita, Seita; Tonari, Masahiro; Fukumoto, Masanori; Suzuki, Hiroyuki; Kobayashi, Takatoshi; Kida, Teruyo; Ikeda, Tsunehiko

    2016-01-01

    Purpose Congenital uveal colobomas, including inferior iris and choroidal colobomas, are associated with microcornea and microphthalmia and often show left-right differences (laterality). The purpose of this study was to report a case of choroidal coloboma associated with left-right differences in diabetic retinopathy (DR). Case This study reports a 59-year-old male with bilateral iris and choroidal colobomas. The colobomatous area in the patient's right eye extended to the macula, and his right eye had been amblyopic since birth. The colobomatous area in his left eye was less extensive and did not involve the macula. Examination of the patient's left eye revealed multiple hemorrhages and hard exudates in the macula due to DR, but examination of his right eye showed almost no changes in DR, thus revealing a marked left-right difference. Optical coherence tomography showed more extensive retinal thinning in the patient's right eye than in his left eye. Fluorescein fundus angiography revealed a retinal nonperfusion area only in the left eye, and panretinal photocoagulation was subsequently performed. Conclusion Our findings show that the reason for the left-right difference in DR was attributed to the more severe choroidal coloboma and retinal thinning in the patient's right eye compared to his left eye, thus reducing oxygen demand, as is also seen in eyes with severe myopia. PMID:27099608

  17. Presence of retinal pericyte-reactive autoantibodies in diabetic retinopathy patients

    PubMed Central

    Zhang, Lingjun; Li, Yan; Payne, John; Srivastava, Sunil; Fan, Xingjun; Fung, John; Li, Xiaorong; Kern, Timothy S.; Lin, Feng

    2016-01-01

    The loss of retinal pericytes (RPCs) is a hallmark of early stage diabetic retinopathy (DR), but the mechanism underlying RPC death is unclear. Although it was postulated in previous studies using bovine RPCs that autoantibodies against RPCs might develop and induce RPC death, it is unknown whether autoantibodies against cell-surface antigens on human RPCs exist in DR patients, whether such autoantibodies contribute to RPC damage/loss, and if they do, through which mechanism. We screened serum samples from DR patients and controls using primary human RPCs and found that that levels of IgGs reactive to RPCs were significantly higher in the DR group than the control group. Serum samples with higher RPC-reactive IgG levels induced more severe complement-mediated RPC damage than those with lower RPC-reactive IgG levels. We also assessed levels of the complement-activation products C3a, C4a and C5a in these serum samples, and found that serum levels of C3a and C5a, but not C4a, were higher in the DR group than control group. These data provide evidence the first time showing that autoantibodies against RPCs can develop in DR patients, and that these autoantibodies could contribute to pericyte damage through complement activation. PMID:26839120

  18. A Randomized Controlled Trial of Conbercept Pretreatment before Vitrectomy in Proliferative Diabetic Retinopathy

    PubMed Central

    Yang, Xiaochun; Wang, Ruili; Mei, Yan; Liu, Jun; Zhang, Ting; Zhao, Haiyan

    2016-01-01

    Purpose. To determine the efficacy and safety of preoperative intravitreal conbercept (IVC) injection before vitrectomy for proliferative diabetic retinopathy (PDR). Methods. 107 eyes of 88 patients that underwent pars plana vitrectomy (PPV) for active PDR were enrolled. All patients were assigned randomly to either preoperative IVC group or control group. Follow-up examinations were performed for three months after surgery. The primary bioactivity measures were severity of intraoperative bleeding, incidence of early and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity (BCVA) levels. The secondary safety measures included intraocular pressure, endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse events. Results. The incidence and severity of intraoperative bleeding were significantly lower in IVC group than in the control group. The average vitreous clear-up time of early recurrent VH was significantly shorter in IVC group compared with that in control group. There was no significant difference in vitreous clear-up time of late recurrent VH between the two groups. Patients that received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1 month after surgery than control group. Moreover, both patients with improved BCVA were greater in IVC group than in control group at each follow-up. Conclusions. Conbercept pretreatment could be an effective adjunct to vitrectomy in accelerating postoperative vitreous clear-up and acquiring stable visual acuity restoration for PDR. PMID:27034822

  19. Formalize clinical processes into electronic health information systems: Modelling a screening service for diabetic retinopathy.

    PubMed

    Eguzkiza, Aitor; Trigo, Jesús Daniel; Martínez-Espronceda, Miguel; Serrano, Luis; Andonegui, José

    2015-08-01

    Most healthcare services use information and communication technologies to reduce and redistribute the workload associated with follow-up of chronic conditions. However, the lack of normalization of the information handled in and exchanged between such services hinders the scalability and extendibility. The use of medical standards for modelling and exchanging information, especially dual-model based approaches, can enhance the features of screening services. Hence, the approach of this paper is twofold. First, this article presents a generic methodology to model patient-centered clinical processes. Second, a proof of concept of the proposed methodology was conducted within the diabetic retinopathy (DR) screening service of the Health Service of Navarre (Spain) in compliance with a specific dual-model norm (openEHR). As a result, a set of elements required for deploying a model-driven DR screening service has been established, namely: clinical concepts, archetypes, termsets, templates, guideline definition rules, and user interface definitions. This model fosters reusability, because those elements are available to be downloaded and integrated in any healthcare service, and interoperability, since from then on such services can share information seamlessly. PMID:26049092

  20. Training set optimization and classifier performance in a top-down diabetic retinopathy screening system

    NASA Astrophysics Data System (ADS)

    Wigdahl, J.; Agurto, C.; Murray, V.; Barriga, S.; Soliz, P.

    2013-03-01

    Diabetic retinopathy (DR) affects more than 4.4 million Americans age 40 and over. Automatic screening for DR has shown to be an efficient and cost-effective way to lower the burden on the healthcare system, by triaging diabetic patients and ensuring timely care for those presenting with DR. Several supervised algorithms have been developed to detect pathologies related to DR, but little work has been done in determining the size of the training set that optimizes an algorithm's performance. In this paper we analyze the effect of the training sample size on the performance of a top-down DR screening algorithm for different types of statistical classifiers. Results are based on partial least squares (PLS), support vector machines (SVM), k-nearest neighbor (kNN), and Naïve Bayes classifiers. Our dataset consisted of digital retinal images collected from a total of 745 cases (595 controls, 150 with DR). We varied the number of normal controls in the training set, while keeping the number of DR samples constant, and repeated the procedure 10 times using randomized training sets to avoid bias. Results show increasing performance in terms of area under the ROC curve (AUC) when the number of DR subjects in the training set increased, with similar trends for each of the classifiers. Of these, PLS and k-NN had the highest average AUC. Lower standard deviation and a flattening of the AUC curve gives evidence that there is a limit to the learning ability of the classifiers and an optimal number of cases to train on.

  1. Planning and developing services for diabetic retinopathy in Sub-Saharan Africa

    PubMed Central

    Poore, Sophie; Foster, Allen; Zondervan, Marcia; Blanchet, Karl

    2015-01-01

    Background: Over the past few decades diabetes has emerged as an important non-communicable disease in Sub-Saharan Africa (SSA). Sight loss from Diabetic Retinopathy (DR) can be prevented with screening and early treatment. The objective of this paper is to outline the required actions and considerations in the planning and development of DR screening services. Methods: A multiple-case study approach was used to analyse five DR screening services in Botswana, Ghana, Tanzania and Zambia. Cases included: two regional screening programmes, two hospital-based screening services and one nationwide screening service. Data was collected using qualitative methodologies including: document analysis, in-depth interviews and observation. The World Health Organization (WHO) Health Systems Framework was adopted as the conceptual framework for analysis. Results: Planning for a sustainable and integrated DR screening programme demanded a health systems approach. Collaboration with representatives from a variety of ministerial departments and professional bodies was required. Evolution of DR screening services may occur in a variety of ways including: increasing geographical coverage, integration into the general healthcare system, and stepwise progression from a passive, opportunistic service to one that systematically and proactively seeks to prevent DR. Lessons learned from the implementation of cervical cancer prevention programmes in resource-poor settings may assist the development of DR programmes in similar settings. Conclusion: To promote good planning of DR screening services and ensure limited resources are used effectively, there is a need to learn from screening programmes in other medical specialities and a need to share experiences between newly-developing DR programmes in resource-poor countries. The WHO Health Systems Framework presents an invaluable tool to ensure a systematic approach to planning DR screening services. PMID:25584349

  2. Diabetes

    MedlinePlus

    ... Diabetic retinopathy Islets of Langerhans Pancreas Insulin pump Type I diabetes Diabetic blood circulation in foot Food and insulin release ... Saunders; 2015:chap 39. Dungan KM. Management of type 2 diabetes mellitus. In: Jameson JL, De Groot LJ, de ... hyperglycemic hyperosmolar syndrome Gestational diabetes Hardening of the ...

  3. HMGB-1 as a Potential Target for the Treatment of Diabetic Retinopathy

    PubMed Central

    Zhao, Hailan; Zhang, Jingzhuang; Yu, Jie

    2015-01-01

    Background Diabetic retinopathy (DR) is one of the most important complications of diabetes mellitus (DM) and is the leading cause of blindness in diabetic patients. Recent studies showed that as important inflammatory mediators, high mobility group box 1 (HMGB-1) is associated with diabetic peripheral neuropathy and can participate in the occurrence and development of DR. This study explored HMGB-1 as a therapeutic target for DR treatment through observing its role in retinal ganglion cells (GRCs) in a high glucose environment. Material/Methods RGCs were randomly divided into 3 groups: the normal control group, the high glucose group, and the siRNA HMGB-1 group. Real-time PCR was used to detect HMGB-1 mRNA expression. ELISA was used to test HMGB-1 protein expression in the supernatant. MTT assay was performed to determine cell proliferation. Real-time PCR and Western blotting were used to analyze TLR4 and NF-κB expression. Results HMGB-1 mRNA was up-regulated (P=0.015) and protein secretion increased (P=0.022) in the high glucose environment. RGCs survival decreased (P=0.026), while TLR4 and NF-κB mRNA (P=0.009 and P=0.017, respectively) and protein expression increased significantly (P=0.041 and P=0.024, respectively). SiRNA HMGB-1 transfection obviously inhibited HMGB-1 mRNA expression (P=0.032), reduced HMGB-1 secretion (P=0.012), and decreased TLR4 and NF-κB mRNA (P=0.033 and P=0.024, respectively) and protein expression (P=0.032; P=0.027, respectively). Compared with the high glucose group, the RGCs survival rate increased significantly (P=0.037). Conclusions As a therapeutic target, HMGB-1 can inhibit inflammation and promote RGCs survival to delay DR progress through the HMGB-1-TLR4-NF-κB signaling pathway. PMID:26454330

  4. Automatic detection of microaneurysms in diabetic retinopathy fundus images using the L*a*b color space.

    PubMed

    Navarro, Pedro J; Alonso, Diego; Stathis, Kostas

    2016-01-01

    We develop an automated image processing system for detecting microaneurysm (MA) in diabetic patients. Diabetic retinopathy is one of the main causes of preventable blindness in working age diabetic people with the presence of an MA being one of the first signs. We transform the eye fundus images to the L*a*b* color space in order to separately process the L* and a* channels, looking for MAs in each of them. We then fuse the results, and last send the MA candidates to a k-nearest neighbors classifier for final assessment. The performance of the method, measured against 50 images with an ophthalmologist's hand-drawn ground-truth, shows high sensitivity (100%) and accuracy (84%), and running times around 10 s. This kind of automatic image processing application is important in order to reduce the burden on the public health system associated with the diagnosis of diabetic retinopathy given the high number of potential patients that need periodic screening. PMID:26831588

  5. An Aqueous Extract of Radix Astragali, Angelica sinensis, and Panax notoginseng Is Effective in Preventing Diabetic Retinopathy

    PubMed Central

    Gao, Dehong; Guo, Yijuan; Li, Xuejun; Li, Xiumin; Li, Zhipeng; Xue, Mei; Ou, Zhimin; Liu, Ming; Yang, Mingxing; Liu, Suhuan; Yang, Shuyu

    2013-01-01

    Diabetic retinopathy (DR), in which inflammation has been implicated playing important roles, is one of the most common diabetes complications. Dang Gui Bu Xue Tang (DBT), an aqueous extract of Radix Astragali and Radix Angelica sinensis, is a classical prescription in Traditional Chinese Medicine for treating inflammation and ischemic diseases. Here, we investigated the effects of a modified recipe of DBT, with addition of Panax notoginseng, in treating diabetic retinopathy. An aqueous extract of Radix Astragali, Radix Angelica sinensis, and Panax notoginseng (RRP) was given to Goto-Kakizaki (GK) rats and streptozotocin-induced Sprague-Dawley (SD) rats. Leukostasis, vascular leakage, and acellular capillaries in retinal vasculature of animals were determined. Expression of retinal inflammatory biomarkers was assessed. We found that RRP reduced leukostasis, acellular capillaries, and vascular leakage compared to diabetic control rats. We also found that RRP decreased the expression of inflammatory factors including IL-1β, IL-6, TNF-α, NF-κB, MCP-1, ICAM-1, or VCAM-1 in the retinas of GK rats and reversed high glucose-induced inhibition of endothelial cell migration and proliferation in vitro. We conclude that RRP has a potent effect in preventing the pathogenesis and/or progression of DR and thus may serve as a promising nontoxic therapeutic approach of DR. PMID:23662142

  6. Serum Oxidized LDL Levels in Type 2 Diabetic Patients with Retinopathy in Mthatha Region of the Eastern Cape Province of South Africa

    PubMed Central

    2016-01-01

    Oxidized low-density lipoprotein (ox-LDL) is a powerful natural prooxidant derived from native LDL by cell-mediated oxidation. Such oxidation occurs more easily in glycated LDL as observed in diabetes mellitus. We evaluated and compared selected biomarkers of oxidative stress and total antioxidant (TAO) levels in type 2 diabetes mellitus (T2DM) patients with and without retinopathy in the Mthatha region of the Eastern Cape Province, South Africa. The participants totaled to 140 and this number comprised 98 diabetic patients on treatment, stratified by diabetes (54) and diabetes with retinopathy (44). Forty-two nondiabetic healthy controls made up the 140. Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), lipid profile, serum ox-LDL, thiobarbituric acid reactive substances (TBARS), and TAO levels were measured. A statistically significant increase in FPG, HbA1c, TBARS, and ox-LDL and a significant decrease in TAO levels were seen in T2DM patients with retinopathy as compared to controls. A significant negative correlation was observed between TAO and ox-LDL levels in the diabetic group. In multiple linear regression analyses, duration of diabetes, triglyceride, TAO, and LDL cholesterol were found to be significantly associated with ox-LDL. In multiple logistic regression analyses, ox-LDL [OR 1.02 (1.01–1.03), P = 0.005] was the only risk factor and was significantly associated with the presence of retinopathy. PMID:27433285

  7. Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice

    PubMed Central

    Liu, Haitao; Patel, Shyam; Roberts, Robin; Berkowitz, Bruce A.; Kern, Timothy S.

    2015-01-01

    early changes of diabetic retinopathy. PMID:26426815

  8. FACTORS ASSOCIATED WITH DIABETIC RETINOPATHY AMONG TYPE 2 DIABETIC PATIENTS: A HOSPITAL BASED CASE-CONTROL STUDY.

    PubMed

    Chaveepojnkamjorn, Wisit; Somjit, Pornpana; Rattanamongkolgul, Suthee; Siri, Sukhontha; Pichainarong, Natchaporn

    2015-03-01

    The objective of this study was to determine factors associated with diabetic retinopathy (DR) among type 2 diabetics in Thailand. We conducted a hospital based case-control study in Nakhon Nayok Province, between August 2008 and July 2010. The subjects were comprised of 230 cases (with DR) and 230 controls (without DR) who were gender and age matched. All subjects were interviewed and their medical records were reviewed. Seventy-five percent of subjects were married and 42% were aged 60-69 years. Fifty-five percent had a primary school education, 27% had no occupation and 67% had family income > 10,000 Baht per month. On multiple logistic regression analysis, factors associated with DR were: having a fasting plasma glucose (FPG) of 141-160 mg/dl, 161-180 mg/dl and > 180 mg/dl [OR = 7.23; 95% confidence interval CI: 2.80-18.72; OR = 4.33; 95% CI: 1.66-11.33, and OR = 3.76; 95% CI: 1.39-10.18], having a HbA1c > 9% (OR = 2.26; 95% CI: 1.15-4.43), having a BMI ≥ 30 kg/m2 (OR = 2.09; 95% CI: 1.04-4.19), and having hypertension (OR = 1.80; 95% CI: 1.19-2.71). Elevated blood sugar, blood pressure and body weight are all associated with DR. Further study is needed to determine if controlling these factors could reduce the prevalence of DR. PMID:26513935

  9. Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique

    PubMed Central

    Agrawal, Rupesh; Smart, Thomas; Nobre-Cardoso, João; Richards, Christopher; Bhatnagar, Rhythm; Tufail, Adnan; Shima, David; H. Jones, Phil; Pavesio, Carlos

    2016-01-01

    A pilot cross sectional study was conducted to investigate the role of red blood cells (RBC) deformability in type 2 diabetes mellitus (T2DM) without and with diabetic retinopathy (DR) using a dual optical tweezers stretching technique. A dual optical tweezers was made by splitting and recombining a single Nd:YAG laser beam. RBCs were trapped directly (i.e., without microbead handles) in the dual optical tweezers where they were observed to adopt a “side-on” orientation. RBC initial and final lengths after stretching were measured by digital video microscopy, and a Deformability index (DI) calculated. Blood from 8 healthy controls, 5 T2DM and 7 DR patients with respective mean age of 52.4yrs, 51.6 yrs and 52 yrs was analysed. Initial average length of RBCs for control group was 8.45 ± 0.25 μm, 8.68 ± 0.49 μm for DM RBCs and 8.82 ± 0.32 μm for DR RBCs (p < 0.001). The DI for control group was 0.0698 ± 0.0224, and that for DM RBCs was 0.0645 ± 0.03 and 0.0635 ± 0.028 (p < 0.001) for DR group. DI was inversely related to basal length of RBCs (p = 0.02). DI of RBC from DM and DR patients was significantly lower in comparison with normal healthy controls. A dual optical tweezers method can hence be reliably used to assess RBC deformability. PMID:26976672

  10. Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique.

    PubMed

    Agrawal, Rupesh; Smart, Thomas; Nobre-Cardoso, João; Richards, Christopher; Bhatnagar, Rhythm; Tufail, Adnan; Shima, David; H Jones, Phil; Pavesio, Carlos

    2016-01-01

    A pilot cross sectional study was conducted to investigate the role of red blood cells (RBC) deformability in type 2 diabetes mellitus (T2DM) without and with diabetic retinopathy (DR) using a dual optical tweezers stretching technique. A dual optical tweezers was made by splitting and recombining a single Nd:YAG laser beam. RBCs were trapped directly (i.e., without microbead handles) in the dual optical tweezers where they were observed to adopt a "side-on" orientation. RBC initial and final lengths after stretching were measured by digital video microscopy, and a Deformability index (DI) calculated. Blood from 8 healthy controls, 5 T2DM and 7 DR patients with respective mean age of 52.4yrs, 51.6 yrs and 52 yrs was analysed. Initial average length of RBCs for control group was 8.45 ± 0.25 μm, 8.68 ± 0.49 μm for DM RBCs and 8.82 ± 0.32 μm for DR RBCs (p < 0.001). The DI for control group was 0.0698 ± 0.0224, and that for DM RBCs was 0.0645 ± 0.03 and 0.0635 ± 0.028 (p < 0.001) for DR group. DI was inversely related to basal length of RBCs (p = 0.02). DI of RBC from DM and DR patients was significantly lower in comparison with normal healthy controls. A dual optical tweezers method can hence be reliably used to assess RBC deformability. PMID:26976672

  11. Does delay in referral of proliferative diabetic retinopathy from the diabetic eye screening programme lead to visual loss?

    PubMed

    Negretti, G S; Amin, R; Webster, L; Egan, C A

    2016-06-01

    AimsTo ascertain the effect on visual acuity (VA) of a delay in Hospital Eye Service (HES) consultation for patients referred with proliferative diabetic retinopathy (PDR; R3) from the Diabetic Eye Screening Programme (DESP).MethodsAll patients referred to Moorfields Eye Hospital from DESP between April and December 2013 with a referral diagnosis of PDR in at least one eye were eligible. Screening programme VA was compared with VA at first HES appointment and final follow-up appointment. Reasons for any VA loss were noted.ResultsA total of 86 patients were included. Of these, 28 (33%) were seen in more than 4 weeks after their DESP referral. At first HES appointment, 39 (45%) patients were graded as having active PDR in at least one eye. Delay in referral did not significantly predict the likelihood of vision loss in all patients referred (χ(2), P=0.49) or in just those patients with a definitive HES diagnosis of active PDR (χ(2), P=1.00). In only 3 patients with active PDR was a delay in presentation thought to have led directly to VA loss.ConclusionsThere may be minimal short-term visual consequence in several weeks of delayed referral for many patients with a diagnosis of R3. However, the national guidance remains important. This is due to the occasional patient at very high risk of vision loss and the many gains for the patients in terms of time to properly assess medical and ocular conditions and counsel and consent them for treatment where necessary. PMID:27055673

  12. Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: effects of laser photocoagulation and angiotensin receptor blockade

    PubMed Central

    Lip, P L; Chatterjee, S; Caine, G J; Hope-Ross, M; Gibson, J; Blann, A D; Lip, G Y H

    2004-01-01

    Background: Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors. Methods: Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA. Results: VEGF (p<0.001) and Ang-2 levels (p<0.001) were significantly higher in 93 diabetic patients compared to 20 healthy controls, with the highest levels in grade 2 and grade 3 diabetic retinopathy (p<0.05). Tie-2 was lower in diabetics compared to controls (p = 0.008), with no significant differences between the diabetic subgroups. Overall, VEGF significantly correlated with Ang-2 (p<0.001) and tie-2 (p = 0.004) but the correlation between Ang-2 and tie-2 levels was not significant (p = 0.065). Among diabetic patients only, VEGF levels were significantly correlated with Ang-2 (p<0.001) and tie-2 (p<0.001); the correlation between Ang-2 and tie-2 levels was also significant (p<0.001). There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy. Conclusion: Increased plasma levels of VEGF and Ang-2, as well as lower soluble tie-2, were found in diabetic patients. The highest VEGF and Ang-2 levels were seen among patients with pre-proliferative and proliferative retinopathy, but there was no relation of tie-2 to the

  13. Association of Urinary Phthalates with Self-Reported Eye Affliction/Retinopathy in Individuals with Diabetes: National Health and Nutrition Examination Survey, 2001–2010

    PubMed Central

    Mamtani, Manju; Curran, Joanne E.; Blangero, John; Kulkarni, Hemant

    2016-01-01

    Background. An epidemiological association between exposure to phthalates and type 2 diabetes (T2D) is known. However, the potential role of environmental phthalates in the complications of T2D is unknown. Methods. Using data from the National Health and Nutrition Examination Survey (NHANES) 2001–2010, we studied the association of 12 urinary phthalate metabolites with self-reported eye affliction/retinopathy in 1,004 participants with diabetes. Data from retinal imaging was used to validate this outcome. Independence of the phthalates→T2D association was studied by adjusting for age, sex, race, marital status, educational attainment, poverty income ratio, physical activity, glycated hemoglobin levels, total serum cholesterol, serum high-density lipoprotein cholesterol, serum triglycerides, blood pressure, duration of diabetes, total calorie intake, and obesity. Results. Self-reported eye affliction/retinopathy had 82% accuracy with Cohen's kappa of 0.31 (p < 0.001). Urinary mono-n-octyl phthalate (MOP) was independently associated with the likelihood of self-reported eye affliction/retinopathy in subjects with T2D after accounting for all the confounders. This significance of this association was robust to the potential misclassification in cases and controls of retinopathy. Further, a significant dose-response relationship between MOP and self-reported eye affliction/retinopathy was demonstrable. Conclusions. We show a novel epidemiological link between the environment and diabetic complications in NHANES 2001–2010 participants. PMID:26798652

  14. Association of Urinary Phthalates with Self-Reported Eye Affliction/Retinopathy in Individuals with Diabetes: National Health and Nutrition Examination Survey, 2001-2010.

    PubMed

    Mamtani, Manju; Curran, Joanne E; Blangero, John; Kulkarni, Hemant

    2016-01-01

    Background. An epidemiological association between exposure to phthalates and type 2 diabetes (T2D) is known. However, the potential role of environmental phthalates in the complications of T2D is unknown. Methods. Using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2010, we studied the association of 12 urinary phthalate metabolites with self-reported eye affliction/retinopathy in 1,004 participants with diabetes. Data from retinal imaging was used to validate this outcome. Independence of the phthalates→T2D association was studied by adjusting for age, sex, race, marital status, educational attainment, poverty income ratio, physical activity, glycated hemoglobin levels, total serum cholesterol, serum high-density lipoprotein cholesterol, serum triglycerides, blood pressure, duration of diabetes, total calorie intake, and obesity. Results. Self-reported eye affliction/retinopathy had 82% accuracy with Cohen's kappa of 0.31 (p < 0.001). Urinary mono-n-octyl phthalate (MOP) was independently associated with the likelihood of self-reported eye affliction/retinopathy in subjects with T2D after accounting for all the confounders. This significance of this association was robust to the potential misclassification in cases and controls of retinopathy. Further, a significant dose-response relationship between MOP and self-reported eye affliction/retinopathy was demonstrable. Conclusions. We show a novel epidemiological link between the environment and diabetic complications in NHANES 2001-2010 participants. PMID:26798652

  15. Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII).

    PubMed

    Hyer, S L; Sharp, P S; Sleightholm, M; Burrin, J M; Kohner, E M

    1989-01-01

    The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2925151

  16. Compound Danshen Dripping Pill for Treating Early Diabetic Retinopathy: A Randomized, Double-Dummy, Double-Blind Study

    PubMed Central

    Luo, Dan; Qin, Yali; Yuan, Wei; Deng, Hui; Zhang, Youhua; Jin, Ming

    2015-01-01

    This randomized, double-dummy, double-blind study was to observe the therapeutic effects of compound Danshen dripping pill (CDDP) in treating early diabetic retinopathy (DR). All the 57 type 2 diabetes cases in nonproliferative diabetic retinopathy (NPDR) stage were divided into two groups randomly: 28 cases treated with CDDP as the treated group and 29 cases treated with calcium dobesilate as the control group. The best corrected visual acuity (BCVA) in the treated group was significantly improved after treatment when compared to that before treatment (P < 0.05). Mean defect (MD) of visual field, hemorrhage area of the fundus, microaneurysm number, fluorescent leakage area, and capillary nonperfusion area evaluated by visual field, fundus photography, and fundus fluorescein angiography in the treated group had the same results as BCVA. However, there was no statistical difference in each index between the two groups. No obvious adverse events with clinical significance occurred. Our present study showed that CDDP has a similar improvement and safety to calcium dobesilate for NPDR. In future DR treatments, CDDP may function as the auxiliary drug. PMID:26457110

  17. The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy

    PubMed Central

    Moran, C.; Tapp, R. J.; Hughes, A. D.; Magnussen, C. G.; Blizzard, L.; Phan, T. G.; Beare, R.; Witt, N.; Venn, A.; Münch, G.; Amaratunge, B. C.; Srikanth, V.

    2016-01-01

    It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy. PMID:27314049

  18. The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy.

    PubMed

    Moran, C; Tapp, R J; Hughes, A D; Magnussen, C G; Blizzard, L; Phan, T G; Beare, R; Witt, N; Venn, A; Münch, G; Amaratunge, B C; Srikanth, V

    2016-01-01

    It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy. PMID:27314049

  19. [Combination of measurement of retinal vascular caliber, adaptive optics and fluorescent angiography in early diagnosis and monitoring of diabetic and hypertensive retinopathy].

    PubMed

    Stepushina, O A; Bol'shunov, A V

    2011-01-01

    15 patients with diabetic and hypertensive retinopathy are examined. Retinal vascular caliber was measured using adaptive multifocal fundus camera (AMFC), fundus camera "Topcon" TRS-NW200 and FAG. Combination of retinal vascular caliber measurement and fundus foto using AMFC in patients with ametropia and astigmatismus showed apparently lower arteriolovenular coefficient (A VC) compared with that estimated using FAG imaging. Retinal vascular caliber measurement using adaptive optics is a highly sensitive method of visualization and monitoring of early signs of diabetic and hypertensive retinopathy. PMID:21721269

  20. Health Insurance Portability and Accountability Act-Compliant Ocular Telehealth Network for the Remote Diagnosis and Management of Diabetic Retinopathy

    SciTech Connect

    Li, Yaquin; Karnowski, Thomas Paul; Tobin Jr, Kenneth William; Giancardo, Luca; Garg, Seema; Fox, Karen; Chaum, Edward

    2011-01-01

    In this article, we present the design and implementation of a regional ocular telehealth network for remote assessment and management of diabetic retinopathy (DR), including the design requirements, network topology, protocol design, system work flow, graphics user interfaces, and performance evaluation. The Telemedical Retinal Image Analysis and Diagnosis Network is a computer-aided, image analysis telehealth paradigm for the diagnosis of DR and other retinal diseases using fundus images acquired from primary care end users delivering care to underserved patient populations in the mid-South and southeastern United States.

  1. Suitability of a Low-Cost, Handheld, Nonmydriatic Retinograph for Diabetic Retinopathy Diagnosis

    PubMed Central

    Quellec, Gwenolé; Bazin, Loïc; Cazuguel, Guy; Delafoy, Ivan; Cochener, Béatrice; Lamard, Mathieu

    2016-01-01

    Purpose We assessed the suitability of a low-cost, handheld, nonmydriatic retinograph, namely the Horus DEC 200, for diabetic retinopathy (DR) diagnosis. Two factors were considered: ease of image acquisition and image quality. Methods One operator acquired fundus photographs from 54 patients using the Horus and AFC-330, a more expensive, nonportable retinograph. Satisfaction surveys were filled out by patients. Then, two retinologists subjectively assessed image quality and graded DR severity in one eye of each patient. Objective image quality indices also were computed. Results During image acquisitions, patients had difficulty locating the fixation target inside the Horus: by default, 53.7% of them had to fixate external points with the contralateral eye, as opposed to none of them using the AFC-330 (P < 0.0001). This issue impacted the duration of image acquisitions. Images obtained by the Horus were of significantly lower quality according to the experts (P = 0.0002 and P = 0.0004) and to the objective criterion (P < 0.0001). As a result, up to 20.4% of eyes were inadequate for interpretation, as opposed to 9.3% using the AFC-330. However, no significant difference was found in terms of DR severity according to both experts (P = 0.557 and P = 0.156). Conclusions The Horus can be used to screen DR, but at the cost of longer examination times and higher proportions of patients referred to an ophthalmologist due to inadequate image quality. Translational Relevance The Horus is adequate to screen DR, for instance in primary care centers or in mobile imaging units. PMID:27134775

  2. Comparison of Snellen and Early Treatment Diabetic Retinopathy Study charts using a computer simulation

    PubMed Central

    Shamir, Reuben R.; Friedman, Yael; Joskowicz, Leo; Mimouni, Michael; Blumenthal, Eytan Z.

    2016-01-01

    AIM To compare accuracy, reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study (ETDRS) charts, two main tools used to measure visual acuity (VA). METHODS A computer simulation was programmed to run multiple virtual patients, each with a unique set of assigned parameters, including VA, false-positive and false-negative error values. For each virtual patient, assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 logMAR units (equivalent to 20/200 to 20/20). Each of 30 000 virtual patients were run ten times on each of the two VA charts. RESULTS Average test duration (expressed as the total number of characters presented during the test ±SD) was 12.6±11.1 and 31.2±14.7 characters, for the Snellen and ETDRS, respectively. Accuracy, defined as the absolute difference (± SD) between the assigned VA and the measured VA, expressed in logMAR units, was superior in the ETDRS charts: 0.12±0.14 and 0.08±0.08, for the Snellen and ETDRS charts, respectively. Reproducibility, expressed as test-retest variability, was superior in the ETDRS charts: 0.23±0.17 and 0.11±0.09 logMAR units, for the Snellen and ETDRS charts, respectively. CONCLUSION A comparison of true (assigned) VA to measured VA, demonstrated, on average, better accuracy and reproducibility of the ETDRS chart, but at the penalty of significantly longer test duration. These differences were most pronounced in the low VA range. The reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies. PMID:26949621

  3. Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy

    PubMed Central

    Kobayashi, Yoshiyuki; Zhou, Yedi; Nakama, Takahito; Ishikawa, Keijiro; Arima, Mitsuru; Nakao, Shintaro; Sassa, Yukio; Takeda, Atsunobu; Hisatomi, Toshio; Ikeda, Yasuhiro; Matsuda, Akira; Sonoda, Koh-hei; Ishibashi, Tatsuro

    2016-01-01

    Purpose We previously demonstrated that tenascin-C was highly expressed in the fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR). However, its role in the pathogenesis of FVMs has not been determined. The purpose of this study was to investigate what role tenascin-C plays in the formation and angiogenesis of FVMs. Methods The level of tenascin-C was determined by sandwich enzyme-linked immunosorbent assay in the vitreous samples collected from patients with PDR and with a macular hole as control. The locations of tenascin-C, α- smooth muscle actin (SMA), CD34, glial fibrillary acidic protein (GFAP), and integrin αV in the FVMs from PDR patients were determined by immunohistochemistry. We also measured the in vitro expression of the mRNA and protein of tenascin-C in vascular smooth muscle cells (VSMCs) stimulated by interleukin (IL)-13. The effects of tenascin-C on cell proliferation, migration, and tube formation were determined in human retinal endothelial cells (HRECs) in culture. Results The mean vitreous levels of tenascin-C were significantly higher in patients with PDR than in patients with a macular hole (p<0.001). Double immunofluorescence analyses of FVMs from PDR patients showed that tenascin-C co-stained FVMs with α-SMA, CD34, and integrin αV but not with GFAP. In addition, IL-13 treatment increased both the expression and secretion of tenascin-C by VSMCs in a dose-dependent manner. Tenascin-C exposure promoted proliferation, migration, and tube formation in HRECs. Tenascin-C neutralizing antibody significantly blocked the tube formation by HRECs exposed to VSMC-IL-13-conditioned medium. Conclusions Our findings suggest that tenascin-C is secreted from VSMCs and promotes angiogenesis in the FVMs associated with PDR. PMID:27186070

  4. Randomized Clinical Trial Evaluating Intravitreal Ranibizumab or Saline for Vitreous Hemorrhage from Proliferative Diabetic Retinopathy

    PubMed Central

    Bhavsar, Abdhish R.; Torres, Karisse; Beck, Roy W.; Bressler, Neil M.; Ferris, Frederick L.; Friedman, Scott M.; Glassman, Adam R.; Maturi, Raj K.; Melia, Michele; Singer, Michael A.; Stockdale, Cynthia R.

    2014-01-01

    Objective To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage (VH) from proliferative diabetic retinopathy (PDR). Main Outcome Cumulative probability of vitrectomy within 16 weeks. Methods Study eyes had VH from PDR precluding panretinal photocoagulation (PRP) completion. Eyes were randomly assigned to 0.5-mg ranibizumab (N = 125) or saline (N = 136) at baseline, 4, and 8 weeks. Results Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab versus 17% with saline (difference 4%, 95% confidence interval −4%–13%) and of complete PRP without vitrectomy by 16-weeks was 44% and 31% respectively (P = 0.05). The mean (±SD) visual acuity improvement from baseline to 12 weeks was 22±23 letters and 16±31 letters respectively (P = 0.04). Recurrent VH occurred within 16 weeks in 6% and 17% respectively (P = 0.01). One eye developed endophthalmitis after saline. Conclusions Overall the 16 week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with VH from PDR. Short term secondary outcomes including visual acuity improvement, increased PRP completion rates, and reduced recurrent VH rates suggest biologic activity of ranibizumab. Long term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab are different than observation alone cannot be determined from this study. Application to Clinical Practice Intravitreal ranibizumab does not appear to reduce vitrectomy rates compared with saline for VH from PDR. PMID:23370902

  5. Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy.

    PubMed

    Mitra, Rajendra Narayan; Nichols, Chance A; Guo, Junjing; Makkia, Rasha; Cooper, Mark J; Naash, Muna I; Han, Zongchao

    2016-08-28

    We recently reported that the Ins2(Akita) mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2(Akita) mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP). The plasmid was compacted by CK30PEG10K into DNA nanoparticles (NPs) for in vivo delivery. Murine endothelial cell line, SVEC4-10, was first transfected with the plasmid. The mRNA levels of VEGF and VEGFR-2 were quantified by qRT-PCR and showed significant reduction in message expression compared with lipofectamine-transfected cells. Transfection of miR200-b suppressed the migration of SVEC4-10 cells. There was a significant inverse correlation between the level of expression of miR200-b and VEGFR-2. Intravitreal injection of miR200-b DNA NPs significantly reduced protein levels of VEGFR-2 as revealed by western blot and markedly suppressed angiogenesis as evaluated by fundus imaging in aged Ins2(Akita) mice even after 3months of post-injection. These findings suggest that NP-mediated miR200-b delivery has negatively regulated VEGFR-2 expression in vivo. PMID:27297781

  6. Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy conditions

    PubMed Central

    Shao, Jun; Yao, Yong

    2016-01-01

    AIM To investigate biological effects of transthyretin (TTR) on the development of neovascularization under simulated diabetic retinopathy (DR) condition associated with high glucose and hypoxia. METHODS Human retinal microvascular endothelial cells (hRECs) were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L; thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 µmol/L CoCl2. The influence of TTR on hRECs and human retinal pigment epithelial cells (hRPECs) was determined by incubating the cells with 4 µmol/L TTR in normal and abnormal media. A co-culture system was then employed to evaluate the effects of hRPECs on hRECs. RESULTS Decreased hRECs and hRPECs were observed under abnormal conditions, including high-glucose and hypoxic media. In addition, hRECs were significantly inhibited by 4 µmol/L exogenous TTR during hyperglycemic culture. During co-culture, hRPECs inhibited hRECs in both the normal and abnormal environments. CONCLUSION hREC growth is inhibited by exogenous TTR under simulated DR environments with high-glucose and hypoxic, particularly in the medium containing 25 mmol/L glucose. hRPECs, which manufacture TTR in the eye, also represses hRECs in the same environment. TTR is predicted to inhibit the proliferation of hRECs and neovascularization. PMID:27366679

  7. Yang Deficiency Body Constitution Acts as a Predictor of Diabetic Retinopathy in Patients with Type 2 Diabetes: Taichung Diabetic Body Constitution Study

    PubMed Central

    Lee, Cheng-Hung; Li, Tsai-Chung; Tsai, Chia-I; Lin, Shih-Yi; Lee, I-Te; Lee, Hsin-Jung; Wu, Ya-Chi; Su, Yi-Chang

    2015-01-01

    Objective. Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus (DM), can cause severe visual impairment and blindness. To prevent the development of DR, identifying the associated risk factors for patient classification is critical. We conducted a cross-sectional study to determine whether body constitution (BC) is an independent predictor of DR. Method. 673 type 2 DM (T2DM) patients were recruited from a medical center, all received DR examination and body constitution questionnaire to assess BC. Other risk factors for DR were also recorded, including life style, history of diabetes, and blood pressure, etc. Multiple logistic regression analysis was conducted to calculate the odds ratios (ORs) for DR. Results. The prevalence of DR was significantly lower in Yang deficiency patients compared with non-Yang deficiency patients (24.69% versus 38.18% P = 0.02). After adjusting for other risk factors, we observed that patients exhibiting Yang deficiency BC were less likely to present with DR (OR = 0.531; 95% confidence interval = 0.312–0.903, P = 0.018). Conclusion. In addition to traditional risk factors, Yang deficiency BC might be an independent predictor of DR among T2DM patients and the results can be used as evidence for traditional Chinese medicine patient classification. PMID:26167195

  8. Factors associated with diabetic retinopathy and nephropathy screening in Korea: the Third and Fourth Korea National Health and Nutrition Examination Survey (KNHANES III and IV).

    PubMed

    Rim, Tyler Hyung Taek; Byun, Il Hwan; Kim, Han Sang; Lee, Sang Yeul; Yoon, Jin Sook

    2013-06-01

    This cross-sectional study was done to identify and determine the socio-demographic and health-related factors associated with diabetic retinopathy and nephropathy screening in Korea. Participants included 2,660 adults, aged 40 or older, with diabetes. Of the 2,660 adults, 998 (37%) and 1,226 (46.1%) had received a diabetic retinopathy and a nephropathy screening within one year, respectively. Regarding retinopathy, subjects older than 65, living in urban areas, with high educational levels, and with self-reported "unhealthy" status were likely to receive annual screening. Subjects living in urban areas, with higher educational levels, with self-reported "fair" or "unhealthy" status, and with 1 to 2 co-morbidities were likely to receive annual nephropathy screening. The Korea Composite Stock Price Index (KOSPI) continued to rise until 2007 when it started to decline over the subsequent years, following the same curve as the diabetic retinopathy and nephropathy screening rates during that time. Together with the financial matter, lack of patient education proved to be a hindrance to diabetes-related screening. The relatively low screening rates in Korea compared to the Western countries are likely to be due to the difference in the health system, economic situations and national demographics. PMID:23772143

  9. Assessment of oxygen saturation in retinal vessels of normal subjects and diabetic patients with and without retinopathy using Flow Oximetry System

    PubMed Central

    Ibrahim, Mohamed A.; Annam, Rachel E.; Sepah, Yasir J.; Luu, Long; Bittencourt, Millena G.; Jang, Hyun S.; Lemaillet, Paul; Munoz, Beatriz; Duncan, Donald D.; West, Sheila; Nguyen, Quan Dong

    2015-01-01

    Purpose To assess oxygen saturation (StO2) in retinal vessels of normal subjects and diabetic patients with and without retinopathy using the modified version of the Flow Oximetry System (FOS) and a novel assessment software. Methods The FOS and novel assessment software were used to determine StO2 levels in arteries and veins located between 1 and 2 mm from the margin of the optic disc and in the macular area. Results Eighteen normal subjects, 15 diabetics without diabetic retinopathy (DM no DR), and 11 with non-proliferative diabetic retinopathy (NPDR) were included in final analysis. The mean [± standard deviation (SD)] StO2 in retinal arteries was 96.9%±3.8% in normal subjects; 97.4%±3.7% in DM no DR; and 98.4%±2.0% in NPDR. The mean venous StO2 was 57.5%±6.8% in normal subjects; 57.4%±7.5% in DM no DR; and 51.8%±6.8% in NPDR. The mean arterial and venous StO2 across the three groups were not statistically different (P=0.498 and P=0.071, respectively). The arterio-venous differences between the three study groups, however, were found to be statistically significant (P=0.015). Pairwise comparisons have demonstrated significant differences when comparing the A-V difference in the NPDR group to either normal subjects (P=0.02) or diabetic patients without DR (P=0.04). Conclusions The arterio-venous difference was greater, and statistically significant, in patients with NPDR when compared to normal subjects and to patients with diabetes and no retinopathy. The mean venous StO2 was lower, but not statistically significant, in NPDR compared with diabetics without retinopathy and with normal subjects. PMID:25694958

  10. Failure to initiate early insulin therapy – A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35)

    PubMed Central

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-01-01

    Context: Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). Aim: The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Materials and Methods: Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Results: Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02–1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). Conclusions: The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control. PMID:27488152

  11. Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

    NASA Technical Reports Server (NTRS)

    Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi; Parsons-Wingerter, Patricia; Oudit, Gavin Y.; Grant, Maria B.

    2016-01-01

    Purpose: In diabetes, the impaired vasoreparative function of Circulating Angiogenic Cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) ACE2 Angiotensin-(1-7) Mas plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy. Methods: Study subjects (n43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5M 96-well chemotaxis cell migration assay. Results: ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls. Conclusions: These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential

  12. Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy

    PubMed Central

    Virgili, Gianni; Menchini, Francesca; Casazza, Giovanni; Hogg, Ruth; Das, Radha R; Wang, Xue; Michelessi, Manuele

    2015-01-01

    Background Diabetic macular oedema (DMO) is a thickening of the central retina, or the macula, and is associated with long-term visual loss in people with diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic fundus photography, leads to moderate visual loss in one of four people within three years. It also showed that grid or focal laser photocoagulation to the macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs has also been used to try to improve vision in people with macular oedema due to DR. Optical coherence tomography (OCT) is based on optical reflectivity and is able to image retinal thickness and structure producing cross-sectional and three-dimensional images of the central retina. It is widely used because it provides objective and quantitative assessment of macular oedema, unlike the subjectivity of fundus biomicroscopic assessment which is routinely used by ophthalmologists instead of photography. Optical coherence tomography is also used for quantitative follow-up of the effects of treatment of CSMO. Objectives To determine the diagnostic accuracy of OCT for detecting DMO and CSMO, defined according to ETDRS in 1985, in patients referred to ophthalmologists after DR is detected. In the update of this review we also aimed to assess whether OCT might be considered the new reference standard for detecting DMO. Search methods We searched the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA) and the NHS Economic Evaluation Database (NHSEED) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1950 to June 2013), Web

  13. Changes in Peripapillary Retinal Nerve Fiber Layer Thickness after Pattern Scanning Laser Photocoagulation in Patients with Diabetic Retinopathy

    PubMed Central

    Park, Yi-Ryeung

    2014-01-01

    Purpose To examine the effects of panretinal photocoagulation (PRP) using a pattern scanning laser (PASCAL) system on the retinal nerve fiber layer (RNFL) thickness in patients with diabetic retinopathy. Methods This retrospective study included 105 eyes with diabetic retinopathy, which consisted of three groups: the PASCAL group that underwent PRP with the PASCAL method (33 eyes), the conventional group that underwent conventional PRP treatment (34 eyes), and the control group that did not receive PRP (38 eyes). The peripapillary RNFL thickness was measured by optical coherence tomography before, six months, and one year after PRP to evaluate the changes in peripapillary RNFL. Results The RNFL thickness in the PASCAL group did not show a significant difference after six months (average 3.7 times, p = 0.15) or one year after the PRP (average 3.7 times, p = 0.086), whereas that in the conventional group decreased significantly after six months (average 3.4 times, p < 0.001) and one year after PRP (average 3.4 times, p < 0.001). Conclusions The results of this study suggest that the PASCAL system may protect against RNFL loss by using less energy than conventional PRP. PMID:24882955

  14. Correlation of Endothelial Nitric Oxide Synthase Gene Polymorphism (GG, TT and GT Genotype) with Proteinuria and Retinopathy in Type 2 Diabetic Patients

    PubMed Central

    Momeni, Ali; Saadatmand, Saeed; Kheiri, Soleiman

    2016-01-01

    Background Nephropathy is the most important leading cause of end stage renal failure in type 2 diabetic patients, so numerous studies were done to diagnose and evaluate risk factors of diabetic nephropathy (DN). Some gene polymorphisms may be associated with progression or regression of DN, so the aim of this study was to compare prevalence of eNOS gene polymorphism in diabetic patients with controls and its association with diabetic nephropathy. Materials and Methods In a cross-sectional study, 94 type 2 diabetic patients and 94 normal participants were enrolled. Patients without retinopathy were excluded from this study. For all of the patients, fasting blood sugar (FBS), 2 hours post-prandial (BS), Blood Urea Nitrogen (BUN), Creatinine (Cr), 24 hours urine protein were measured in the case group. Endothelial nitric oxide synthetase gene polymorphism was evaluated in the case and control groups. Results There was no significant difference based on age and sex between patients in case and control groups. GG genotype of eNOS was less common in the patient group compared to control group. There was no difference between prevalence of TT, GT or GG genotype based on age and sex. There was no correlation between diabetic retinopathy or proteinuria and genotypes of eNOs. Conclusion The study showed that in type 2 diabetic patients, NOS gene polymorphism was more common compared to normal population; however, there is no correlation between this gene polymorphism and proteinuria or retinopathy in these patients. PMID:27042499

  15. C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy

    PubMed Central

    Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pešić, Milica; Babić, Gordana Stanković; Milenković, Svetislav; Risimić, Dijana

    2014-01-01

    The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy. PMID:25172979

  16. Perception of care and barriers to treatment in individuals with diabetic retinopathy in India: 11-city 9-state study

    PubMed Central

    Shukla, Rajan; Gudlavalleti, Murthy V. S.; Bandyopadhyay, Souvik; Anchala, Raghupathy; Gudlavalleti, Aashrai Sai Venkat; Jotheeswaran, A. T.; Ramachandra, Srikrishna S.; Singh, Vivek; Vashist, Praveen; Allagh, Komal; Ballabh, Hira Pant; Gilbert, Clare E.

    2016-01-01

    Background: Diabetic retinopathy is a leading cause of visual impairment. Low awareness about the disease and inequitable distribution of care are major challenges in India. Objectives: Assess perception of care and challenges faced in availing care among diabetics. Materials and Methods: The cross-sectional, hospital based survey was conducted in eleven cities. In each city, public and private providers of eye-care were identified. Both multispecialty and standalone facilities were included. Specially designed semi-open ended questionnaires were administered to the clients. Results: 376 diabetics were interviewed in the eye clinics, of whom 62.8% (236) were selected from facilities in cities with a population of 7 million or more. The mean duration of known diabetes was 11.1 (±7.7) years. Half the respondents understood the meaning of adequate glycemic control and 45% reported that they had visual loss when they first presented to an eye facility. Facilities in smaller cities and those with higher educational status were found to be statistically significant predictors of self-reported good/adequate control of diabetes. The correct awareness of glycemic control was significantly high among attending privately-funded facilities and higher educational status. Self-monitoring of glycemic status at home was significantly associated with respondents from larger cities, privately-funded facilities, those who were better educated and reported longer duration of diabetes. Duration of diabetes (41%), poor glycemic control (39.4%) and age (20.7%) were identified as the leading causes of DR. The commonest challenges faced were lifestyle/behavior related. Conclusions: The findings have significant implications for the organization of diabetes services in India. PMID:27144135

  17. Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab

    PubMed Central

    Li, Jiu-Ke; Wei, Fang; Jin, Xiao-Hong; Dai, Yuan-Min; Cui, Hu-Shan; Li, Yu-Min

    2015-01-01

    AIM To evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR). METHODS This study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively. RESULTS In PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis. CONCLUSION We found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB

  18. Evaluation of diabetic retinopathy screening using a non-mydriatic retinal digital camera in primary care settings in south Israel.

    PubMed

    Mizrachi, Yossi; Knyazer, Boris; Guigui, Sara; Rosen, Shirley; Lifshitz, Tova; Belfair, Nadav; Klemperer, Itamar; Schneck, Marina; Levy, Jaime

    2014-08-01

    To evaluate the effectiveness of the non-mydriatic digital camera for diabetic retinopathy (DR) screening. Secondary purposes of the study were to characterize diabetic patients being screened for the presence of DR and to calculate the sensitivity, specificity, and positive predictive value of the test. All 6,962 consecutive patients with type 2 diabetes undergoing non-mydriatic digital retinal photography between January 1, 2009 and June 30, 2010 in eight community health clinics in the south of the country were included. Comparison of a random sample of patients who underwent non-mydriatic retinal photography, and who were also examined by an ophthalmologist with pupil dilation was also performed. The average age of all patients was 64.2 years. A total of 5,960 cases (85.6 % of all photographs) were of adequate quality for the diagnosis. DR of any degree was found in 1,092 (18.3 %) patients. Normal fundus pictures were found in 49.4 % of patients. In 32.2 % of cases, non-DR pathologies were found. Among cases in which DR was found, 73.3 % (801 cases) had mild non-proliferative retinopathy (NPDR), 7.1 % (77 cases) had moderate NPDR, 6.8 % (74 cases) had proliferative retinopathy, and 12.8 % (140 cases) had diabetic macular edema. Older patients had more chance of having poor quality pictures (p < 0.001 between patients older and younger than 70 years). When non-mydriatic fundus photography was compared with dilated fundus examination by an ophthalmologist, sensitivity of 99.3 %, specificity of 88.3 %, and positive predictive value of 85.3 % were found. Non-mydriatic digital retinal photography is an efficient method for DR screening. The test has high sensitivity and specificity. The test, as performed in community health centers in the south of the country, contributed to the early diagnosis of >1,000 cases of DR. Many patients can be followed up in a fast and efficient way, although the test cannot replace a complete eye examination after pupil dilation mainly

  19. Programmed Death 1 (PD-1) is involved in the development of proliferative diabetic retinopathy by mediating activation-induced apoptosis

    PubMed Central

    Fang, Mengyuan; Meng, Qianli; Wang, Liya; Zhao, Zhaoxia; Zhang, Liang; Kuang, Jian; Cui, Ying; Mai, Liping; Zhu, Jiening

    2015-01-01

    Purpose Recent studies revealed that immunological mechanisms play a prominent role in the pathogenesis of proliferative diabetic retinopathy (PDR). Given the importance of the immune response in PDR and the significance of the programmed death 1 (PD-1) pathway as an immune regulatory pathway, the aim of this study is to determine the expression and functional characteristics of the PD-1 pathway in peripheral blood lymphocytes from patients with PDR. Methods Peripheral blood lymphocytes were obtained from patients with PDR, age-matched patients with diabetes mellitus and no diabetic retinopathy (DM-NDR), and controls. The mRNA expression of PD-1 and its ligands were determined using real-time PCR. The frequencies of PD-1 and its ligands, activation-induced apoptosis, IFN-γ, and IL-4 were determined by flow cytometry. Results The PD-1 mRNA expression markedly decreased, while the frequency of PD-1+ cells increased in the PDR group compared with the DM-NDR and control groups. The expression of PD-ligand 1 (PD-L1) mRNA and PD-L1+ cells in the PDR group was lower than that in the other two groups. In the PDR group, the frequency of Annexin V+PI- and Annexin V+PI-PD-1+ cells increased, while the frequency of Annexin V+PI-PD-L1+ cells decreased. Although their expression was upregulated, the ratio of PD-1+ IFN-γ+ to PD-1+IL-4+ cells in the PDR group was not significantly different to that in the DM-NDR and control groups. Conclusions These results suggest that PD-1 is involved in the development of PDR by mediating activation-induced apoptosis. PMID:26321864

  20. Neuron-derived semaphorin 3A is an early inducer of vascular permeability in diabetic retinopathy via neuropilin-1.

    PubMed

    Cerani, Agustin; Tetreault, Nicolas; Menard, Catherine; Lapalme, Eric; Patel, Chintan; Sitaras, Nicholas; Beaudoin, Felix; Leboeuf, Dominique; De Guire, Vincent; Binet, François; Dejda, Agnieszka; Rezende, Flavio A; Miloudi, Khalil; Sapieha, Przemyslaw

    2013-10-01

    The deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in Tg(Cre-Esr1)/Nrp1(flox/flox) conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR. PMID:24093675

  1. Toll-like receptor 4 in bone marrow-derived cells contributes to the progression of diabetic retinopathy.

    PubMed

    Wang, Hui; Shi, Haojun; Zhang, Jing; Wang, Guoliang; Zhang, Jinxiang; Jiang, Fagang; Xiao, Qing

    2014-01-01

    Diabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM) induction by streptozotocin (STZ) treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α). Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR. PMID:25214718

  2. The Role of Plasma Kallikrein-Kinin Pathway in the Development of Diabetic Retinopathy: Pathophysiology and Therapeutic Approaches.

    PubMed

    Abdulaal, Marwan; Haddad, Nour Maya N; Sun, Jennifer K; Silva, Paolo S

    2016-01-01

    Diabetic retinal disease is characterized by a series of retinal microvascular changes and increases in retinal vascular permeability that lead to development of diabetic retinopathy (DR) and diabetic macular edema (DME), respectively. Current treatment strategies for DR and DME are mostly limited to vascular endothelial growth factor (VEGF) inhibitors and laser photocoagulation. These treatment modalities are not universally effective in all patients, and potential side effects persist in a significant portion of patients. The plasma kallikrein-kinin system (KKS) is one of the pathways that has been identified in the vitreous in proliferative DR and DME. Preclinical studies have shown that the activation of intraocular KKS induces retinal vascular permeability, vasodilation, and retinal thickening. Proteomic analysis from vitreous of eyes with DME has shown that KKS and VEGF pathways are potentially independent biologic pathways. Furthermore, proteins associated with DME in the vitreous were significantly more correlated with the KKS pathway compared to VEGF pathway. Preclinical experiments on diabetic animals showed that inhibition of KKS components was found to be an effective approach to decrease retinal vascular permeability. An initial phase I human trial of a novel plasma kallikrein inhibitor for the treatment of DME is currently ongoing to test the safety of this approach and serves as an initial step in the translation of basic science discovery into an innovative clinical intervention. PMID:26959125

  3. Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications.

    PubMed

    Monnier, Vincent M; Sun, Wanjie; Sell, David R; Fan, Xingjun; Nemet, Ina; Genuth, Saul

    2014-01-01

    Advanced glycation end products (AGEs) represent a family of protein, peptide, amino acid, nucleic acid and lipid adducts formed by the reaction of carbonyl compounds derived directly or indirectly from glucose, ascorbic acid and other metabolites such as methylglyoxal. AGE formation in diabetes is of growing importance for their role as markers and potential culprits of diabetic complications, in particular retinopathy, nephropathy and neuropathy. Development of sensitive and specific assays utilizing liquid chromatography mass spectrometry with isotope dilution method has made it possible to detect and quantitate non-UV active AGEs such as carboxymethyl-lysine and glucosepane, the most prevalent AGE and protein crosslink of the extracellular matrix. Below we review studies on AGE formation in two skin biopsies obtained near the closeout of the Diabetes Control and Complications Trial (DCCT), one of which was processed in 2011 for assay of novel AGEs. The results of these analyses show that while several AGEs are associated and predict complication progression, the glucose/fructose-lysine/glucosepane AGE axis is one of the most robust markers for microvascular disease, especially retinopathy, in spite of adjustment for past or future average