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Sample records for advanced diabetic retinopathy

  1. Microvascular complications and diabetic retinopathy: recent advances and future implications.

    PubMed

    Barot, Megha; Gokulgandhi, Mitan R; Patel, Sulabh; Mitra, Ashim K

    2013-03-01

    Retinal microvascular alterations have been observed during diabetic retinopathy (DR) due to the retinal susceptibility towards subtle pathological alterations. Therefore, retinal microvascular pathology is essential to understand the nature of retinal degenerations during DR. In this review, the role of retinal microvasculature complications during progression of DR, along with recent efforts to normalize such alterations for better therapeutic outcome, will be underlined. In addition, current therapeutics and future directions for advancement of standard treatment for DR patients will be discussed. PMID:23464520

  2. 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

  3. 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.

  4. 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

  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. Diabetic retinopathy.

    PubMed

    Moreno, A; Lozano, M; Salinas, P

    2013-03-01

    This paper describes the importance of diabetic retinopathy in the loss of visual function. We exposed the most important risk factors, such as diabetes duration, poor metabolic control, pregnancy, puberty, hypertension, poor control of blood lipids, renal disease, and sleep apnea syndrome. We describe the pathogenesis of the disease, small retinal vessel microangiopathies which produce extravasation, edema and ischemia phenomena. We put special emphasis on the vascular endothelial growth factor (VEGF) and its pathogenic importance. They are also described the main clinical symptoms as microaneurysms, intraretinal hemorrhages, hard and soft exudates, intraretinal microvascular abnormalities (IRMA), venous disorders, formation of new vessels and diabetic macular edema (the latter being the most common cause of vision loss). Finally we describe the latest diagnostic techniques and eye treatment, with special emphasis on obesity surgery importance as more important preventive factor to eliminate the predisposing and precipitating disease symptoms.

  7. Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss.

    PubMed

    Barber, Alistair J

    2015-06-01

    Diabetic retinopathy (DR) is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of cells in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

  8. Genetics of Diabetic Retinopathy

    PubMed Central

    Cho, Heeyoon

    2014-01-01

    Diabetic retinopathy (DR) is a polygenic disorder. Twin studies and familial aggregation studies have documented clear familial clustering. Heritability has been estimated to be as high as 27% for any DR and 52% for proliferative diabetic retinopathy (PDR), an advanced form of the disease. Linkage analyses, candidate gene association studies and genome-wide association studies (GWAS) performed to date have not identified any widely reproducible risk loci for DR. Combined analysis of the data from multiple GWAS is emerging as an important next step to explain the unaccounted heritability. Key factors to future discovery of the genetic underpinnings of DR are precise DR ascertainment, a focus on the more heritable disease forms such as PDR, stringent selection of control participants with regards to duration of diabetes, and methods that allow combination of existing datasets from different ethnicities to achieve sufficient sample sizes to detect variants with modest effect sizes. PMID:24952107

  9. 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.

  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. Pathophysiology of Diabetic Retinopathy

    PubMed Central

    Tarr, Joanna M.; Kaul, Kirti; Chopra, Mohit; Kohner, Eva M.; Chibber, Rakesh

    2013-01-01

    Diabetes is now regarded as an epidemic, with the population of patients expected to rise to 380 million by 2025. Tragically, this will lead to approximately 4 million people around the world losing their sight from diabetic retinopathy, the leading cause of blindness in patients aged 20 to 74 years. The risk of development and progression of diabetic retinopathy is closely associated with the type and duration of diabetes, blood glucose, blood pressure, and possibly lipids. Although landmark cross-sectional studies have confirmed the strong relationship between chronic hyperglycaemia and the development and progression of diabetic retinopathy, the underlying mechanism of how hyperglycaemia causes retinal microvascular damage remains unclear. Continued research worldwide has focussed on understanding the pathogenic mechanisms with the ultimate goal to prevent DR. The aim of this paper is to introduce the multiple interconnecting biochemical pathways that have been proposed and tested as key contributors in the development of DR, namely, increased polyol pathway, activation of protein kinase C (PKC), increased expression of growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), haemodynamic changes, accelerated formation of advanced glycation endproducts (AGEs), oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and subclinical inflammation and capillary occlusion. New pharmacological therapies based on some of these underlying pathogenic mechanisms are also discussed. PMID:24563789

  13. 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)

  14. 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, ...

  15. 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

  16. Advanced glycation end products (AGEs) and their receptor (RAGE) system in diabetic retinopathy.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Matsui, Takanori

    2006-03-01

    Vascular complications are a leading cause of blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. There is a growing body of evidence that formation and accumulation of advanced glycation end products (AGEs) progress during normal aging, and at an extremely accelerated rate in diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Furthermore, the interaction by AGEs of their receptor, RAGE, activates down-stream signaling and evokes inflammatory responses in vascular wall cells. Therefore, inhibition of AGE formation or blockade of the RAGE signaling may be a promising target for therapeutic intervention to prevent diabetic vascular complications. This review discusses the molecular mechanisms of diabetic retinopathy, especially focusing on the AGE-RAGE system. Several types of inhibitors of the AGE-RAGE system and their therapeutic implications are also reviewed here. PMID:16712466

  17. Zinc and Diabetic Retinopathy

    PubMed Central

    Miao, Xiao; Sun, Weixia; Miao, Lining; Fu, Yaowen; Wang, Yonggang; Su, Guanfang; Liu, Quan

    2013-01-01

    Zinc (Zn) is an important nutrient that is involved in various physiological metabolisms. Zn dyshomeostasis is often associated with various pathogeneses of chronic diseases, such as metabolic syndrome, diabetes, and related complications. Zn is present in ocular tissue in high concentrations, particularly in the retina and choroid. Zn deficiencies have been shown to affect ocular development, cataracts, age-related macular degeneration, and even diabetic retinopathy. However, the mechanism by which Zn deficiency increases the prevalence of diabetic retinopathy remains unclear. In addition, due to the negative effect of Zn deficiency on the eye, Zn supplementation should prevent diabetic retinopathy; however, limited available data do not always support this notion. Therefore, the goal of this paper was to summarize these pieces of available information regarding Zn prevention of diabetic retinopathy. Current theories and possible mechanisms underlying the role of Zn in the eye-related diseases are discussed. The possible factors that affect the preventive effect of Zn supplementation on diabetic retinopathy were also discussed. PMID:23671870

  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. 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.

  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. 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

  2. Diabetic Retinopathy in Native and Nonnative Canadians

    PubMed Central

    Ross, Stuart A.; McKenna, Anne; Mozejko, Sheila; Fick, Gordon H.

    2007-01-01

    High prevalence rates of type 2 diabetes are being observed in native Canadian communities. It is believed that native populations have a higher prevalence rate of vascular complications than nonnatives. The Southern Alberta Study of Diabetic Retinopathy (DR) examined the prevalence and incidence of DR and associated metabolic abnormalities in native and nonnative subjects. Prevalence rates of DR in type 2 diabetic native and nonnative subjects were identical, with a prevalence rate of 40%. Native subjects with retinopathy, however, tended to have more advanced changes of retinopathy compared to the nonnative subjects. Key factors such as A1c, blood pressure, duration of diabetes, and lipid values were not significantly different between the two cohorts. These data indicate that ethnicity does play a role in the development and severity of DR but potential risk factors that may affect the development of retinopathy are not significantly different between native and nonnative groups. PMID:18317512

  3. 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

  4. Prevalence of undiagnosed diabetic retinopathy among inpatients with diabetes: the diabetic retinopathy inpatient study (DRIPS)

    PubMed Central

    Kovarik, Jessica J; Eller, Andrew W; Willard, Lauren A; Ding, Jiaxi; Johnston, Jann M; Waxman, Evan L

    2016-01-01

    Objective To determine the prevalence and risk factors of diabetic retinopathy in the inpatient diabetic population in the USA and to determine the barriers to ophthalmic examinations and treatment among this population. Research design and methods A cross-sectional analysis of 113 inpatients with diabetes mellitus admitted to an inner city community teaching hospital in Pittsburgh. Digital fundus photographs of the posterior pole were taken of each eye after pharmacological dilation. Presence, absence and severity of diabetic retinopathy and macular edema were graded on the basis of internationally accepted criteria. An investigator-administered questionnaire and review of the medical record were used to obtain data about patient demographics, clinical characteristics and barriers to ophthalmic care. The association between these data and the presence of diabetic retinopathy was tested. Results The estimated prevalence of diabetic retinopathy in the inpatient population was 44% (95% CI 34% to 53%). The prevalence of previously undiagnosed diabetic retinopathy and sight-threatening retinopathy was 25% (95% CI 17% to 33%) and 19% (95% CI 11% to 26%), respectively. Renal disease was independently associated with the presence of diabetic retinopathy (OR, 3.86; 95% CI 1.22 to 12.27), as well as a longer duration of diabetes (OR, 1.08 per year; 95% CI 1.014 to 1.147). Diabetic retinopathy was seen in 15 of 17 patients admitted with diabetic foot ulcers or osteomyelitis. Frequently reported barriers to ophthalmic examinations included lack of transportation and physical disability. Conclusions The prevalence of diabetic retinopathy and sight-threatening diabetic retinopathy in the inpatient population is likely significantly higher than in the general diabetic population in the USA. These patients have barriers to care that need to be addressed to make standard of care ophthalmic examinations and treatment possible in this population. PMID:26925238

  5. 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.

  6. The role of CTGF in diabetic retinopathy.

    PubMed

    Klaassen, Ingeborg; van Geest, Rob J; Kuiper, Esther J; van Noorden, Cornelis J F; Schlingemann, Reinier O

    2015-04-01

    Connective tissue growth factor (CTGF, CCN2) contributes to fibrotic responses in diabetic retinopathy, both before clinical manifestations occur in the pre-clinical stage of diabetic retinopathy (PCDR) and in proliferative diabetic retinopathy (PDR), the late clinical stage of the disease. CTGF is a secreted protein that modulates the actions of many growth factors and extracellular matrix (ECM) proteins, leading to tissue reorganization, such as ECM formation and remodeling, basal lamina (BL) thickening, pericyte apoptosis, angiogenesis, wound healing and fibrosis. In PCDR, CTGF contributes to thickening of the retinal capillary BL and is involved in loss of pericytes. In this stage, CTGF expression is induced by advanced glycation end products, and by growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β. In PDR, the switch from neovascularization to a fibrotic phase - the angio-fibrotic switch - in PDR is driven by CTGF, in a critical balance with vascular endothelial growth factor (VEGF). We discuss here the roles of CTGF in the pathogenesis of DR in relation to ECM remodeling and wound healing mechanisms, and explore whether CTGF may be a potential novel therapeutic target in the clinical management of early as well as late stages of DR.

  7. [Growth factors in proliferative diabetic retinopathy].

    PubMed

    Ioniţă, M

    1997-01-01

    This work presents the possible implications of the angiogenic growth factors and some cell mediators in the initiation and development of the neovascular proliferation in diabetic retinopathy. According to the physiopathologic theories stated above, that are implied in the generation of proliferative diabetic retinopathy, here are some therapeutic experiments based on the action of the angiogenic growth factors. PMID:9409959

  8. Electrophysiological changes in juvenile diabetics without retinopathy.

    PubMed

    Juen, S; Kieselbach, G F

    1990-03-01

    Several components of the electroretinogram were studied in 31 juvenile diabetics and 15 age-matched normal controls. The diabetic group consisted of 18 patients without retinopathy and 13 with mild background retinopathy. Oscillatory potentials were measured at low-stimulation energies. Significantly reduced amplitudes and component-specific delayed peak implicit times were found in both diabetic groups compared with the data from the controls. Similar results were obtained in the photopic and scotopic electroretinogram. From these findings, we suggest that retinal dysfunction is already present in juvenile diabetics without photographic evidence of retinopathy after a mean duration of diabetes of 7 years. PMID:2310337

  9. [Proliferative diabetic retinopathy -- therapeutic approach (clinical case)].

    PubMed

    Burcea, M; Muşat, Ovidiu; Mahdi, Labib; Gheorghe, Andreea; Spulbar, F; Gobej, I

    2014-01-01

    We present the case of a 54 year old pacient diagnosed with neglected insulin dependent diabetes and proliferative diabetic retinopathy. Surgery was recommended and we practiced posterior vitrectomy, endolaser and heavy silicone oil endotamponade. Post-operative evolution was favorable.

  10. 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

  11. The National Diabetic Retinopathy Laser Treatment Audit. II. Proliferative retinopathy.

    PubMed

    Bailey, C C; Sparrow, J M; Grey, R H; Cheng, H

    1998-01-01

    The National Diabetic Retinopathy Laser Treatment Audit is a prospective survey of laser treatment for diabetic retinopathy throughout the United Kingdom. This paper presents data on 284 patients who were undergoing their first panretinal photocoagulation for proliferative retinopathy during a 2 month period in 1995, describing the demographic features, the level of systematic screening, the sources of referral, and the waiting times. For those cases where proliferative retinopathy was present at the first ophthalmology outpatient visit, the retinopathy was detected as a result of systematic screening in 46.8%, whilst 28.7% presented symptomatically. Of these patients 28.4% waited for more than 12 weeks from referral to the time of laser treatment, but once the patient had been listed for laser treatment this was performed within 8 weeks in 95.3%. The retinopathy features and the type of treatment given are also described. Compared with the DRS and ETDRS recommendations, at least 32.5-40.2% of eyes may be undertreated initially, and for those with high-risk characteristics these figures were at least 30.8-38.5%.

  12. Telehealth practice recommendations for diabetic retinopathy.

    PubMed

    Cavallerano, Jerry; Lawrence, Mary G; Zimmer-Galler, Ingrid; Bauman, Wendell; Bursell, Sven; Gardner, W Kelley; Horton, Mark; Hildebrand, Lloyd; Federman, Jay; Carnahan, Lisa; Kuzmak, Peter; Peters, John M; Darkins, Adam; Ahmed, Jehanara; Aiello, Lloyd M; Aiello, Lloyd P; Buck, Gary; Cheng, Ying Ling; Cunningham, Denise; Goodall, Eric; Hope, Ned; Huang, Eugene; Hubbard, Larry; Janczewski, Mark; Lewis, J W L; Matsuzaki, Hiro; McVeigh, Francis L; Motzno, Jordana; Parker-Taillon, Diane; Read, Robert; Soliz, Peter; Szirth, Bernard; Vigersky, Robert A; Ward, Thomas

    2004-01-01

    Telehealth holds the promise of increased adherence to evidenced-based medicine and improved consistency of care. Goals for an ocular telehealth program include preserving vision, reducing vision loss, and providing better access to medicine. Establishing recommendations for an ocular telehealth program may improve clinical outcomes and promote informed and reasonable patient expectations. This document addresses current diabetic retinopathy telehealth clinical and administrative issues and provides recommendations for designing and implementing a diabetic retinopathy ocular telehealth care program. The recommendations also form the basis for evaluating diabetic retinopathy telehealth techniques and technologies. Recommendations in this document are based on careful reviews of current evidence, medical literature and clinical practice. They do not, however, replace sound medical judgment or traditional clinical decision-making. "Telehealth Practice Recommendations for Diabetic Retinopathy" will be annually reviewed and updated to reflect evolving technologies and clinical guidelines. PMID:15689653

  13. Retinal fibrosis in diabetic retinopathy.

    PubMed

    Roy, Sayon; Amin, Shruti; Roy, Sumon

    2016-01-01

    In response to injury, reparative processes are triggered to restore the damaged tissue; however, such processes are not always successful in rebuilding the original state. The formation of fibrous connective tissue is known as fibrosis, a hallmark of the reparative process. For fibrosis to be successful, delicately balanced cellular events involving cell proliferation, cell migration, and extracellular matrix (ECM) remodeling must occur in a highly orchestrated manner. While successful repair may result in a fibrous scar, this often restores structural stability and functionality to the injured tissue. However, depending on the functionality of the injured tissue, a fibrotic scar can have a devastating effect. For example, in the retina, fibrotic scarring may compromise vision and ultimately lead to blindness. In this review, we discuss some of the retinal fibrotic complications and highlight mechanisms underlying the development of retinal fibrosis in diabetic retinopathy.

  14. ERK5 Mediated Signalling in Diabetic Retinopathy

    PubMed Central

    Wu, Yuexiu; Chakrabarti, Subrata

    2015-01-01

    Diabetic retinopathy is the lead among causes of blindness in North America. Glucose-induced endothelial injury is the most important cause of diabetic retinopathy and other vascular complications. Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (BMK1), is a member of mitogen-activated protein kinases (MAPK) family. Physiologically, it is critical for cardiovascular development and maintenance of the endothelial cell integrity. Extracellular signal-regulated kinase 5 is protective for endothelial cells under stimulation and stress. Decreased activation of ERK5 results in increased endothelial cell death. Extracellular signal-regulated kinase 5 signaling may be subject to alteration by hyperglycemia, while signaling pathway including ERK5 may be subject to alteration during pathogenesis of diabetic complications. In this review, the role of ERK5 in diabetic macro- and microvascular complications with a focus on diabetic retinopathy are summarized and discussed. PMID:25861671

  15. Proliferative diabetic retinopathy in typical retinitis pigmentosa.

    PubMed

    Preethi, Srinivasaraghavan; Rajalakshmi, Adithyapuram Ramachandran

    2015-01-01

    A 39-year-old woman with typical retinitis pigmentosa (RP) for 9 years and a positive family history of night blindness was diagnosed with diabetes mellitus (DM). She developed proliferative diabetic retinopathy (PDR) during the course of disease. She was promptly managed with pan retinal photocoagulation (PRP). PDR developing in a case of typical RP is extremely rare and has not been reported in the literature to date. Recognition of this rare, vision threatening complication, points out a definite need to further look deep into the pathogenesis of diabetic retinopathy. PMID:26021380

  16. Replication Analysis for Severe Diabetic Retinopathy

    PubMed Central

    Grassi, Michael A.; Tikhomirov, Anna; Ramalingam, Sudha; Lee, Kristine E.; Hosseini, S. M.; Klein, Barbara E. K.; Klein, Ronald; Lussier, Yves A.; Cox, Nancy J.; Nicolae, Dan L.

    2012-01-01

    Purpose. The purpose of this study is to attempt to replicate the top single nucleotide polymorphism (SNP) associations from a previous genome-wide association study (GWAS) for the sight-threatening complications of diabetic retinopathy in an independent cohort of diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Methods. This study included 469 type 1 diabetic, Caucasian subjects from WESDR. Cases (n = 208) were defined by prior laser treatment for either proliferative diabetic retinopathy or diabetic macular edema. Controls (n = 261) were all other subjects in the cohort. Three hundred eighty-nine SNPs were tested for association using the Illumina GoldenGate custom array. A retinopathy-only subanalysis was conducted in 437 subjects by removing those with end-stage renal disease. Evaluation for association between cases and controls was conducted by using chi-square tests. A combined analysis incorporated the results from WESDR with the prior GWAS. Results. No associations were significant at a genome-wide level. The analysis did identify SNPs that can be pursued in future replication studies. The top association was at rs4865047, an intronic SNP, in the gene CEP135 (P value 2.06 × 10−5). The top association from the subanalysis was at rs1902491 (P value 2.81 × 10−5), a SNP that sits upstream of the gene NPY2R. Conclusions. This study nominates several novel genetic loci that may be associated with severe diabetic retinopathy. In order to confirm these findings, replication and extension in additional cohorts will be necessary as susceptibility alleles for diabetic retinopathy appear to be of modest effect. PMID:22427569

  17. 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

  18. Toxic action of advanced glycation end products on cultured retinal capillary pericytes and endothelial cells: relevance to diabetic retinopathy.

    PubMed

    Chibber, R; Molinatti, P A; Rosatto, N; Lambourne, B; Kohner, E M

    1997-02-01

    The toxic effects of advanced glycation end products (AGEs) on bovine retinal capillary pericytes (BRP) and endothelial cells (BREC) were studied. AGE-modified bovine serum albumin (AGE-BSA) was toxic to BRP. At a concentration of 500 micrograms/ml it reduced the BRP number to 48 +/- 3% (p < 0.05) of untreated controls, as determined by cell counting with haemocytometer. AGE-BSA was also toxic to bovine aortic endothelial cells (BAEC) reducing cell number to 84 +/- 3.1% of untreated controls. Under similar conditions, low concentrations (62.5 micrograms/ml) of AGE-BSA were mitogenic to BREC increasing the cell proliferation to 156 +/- 11% (p < 0.05) above that of untreated controls. At a higher dose of 500 micrograms/ml AGE-BSA decreased the proliferation of BREC to 85 +/- 6% of untreated controls. Immunoblot analysis demonstrated that BRP and BREC express the p60 AGE-receptor. Retinal capillary bed from the human also stained positively for the p60 AGE-receptor. Addition of 0.25 micrograms/ml of p60 AGE-receptor antibody was able to block the effects of AGE-BSA on BRP and BREC. The level of binding of [125I]-labelled AGE-BSA to the cell surface was small but significant among the three cell types. There was also an increase in the internalized pool of radioligand in BRP and BREC but this was very much lower than in BAEC. In all the cell types the internalized pool of [125I]-labelled AGE-BSA was much larger than the amount associated with the cell surface. Degradation products were not detected in the media over the 24-h incubation of the cells with [125I]AGE-BSA. The binding of [125I]-labelled AGE-BSA to the cell surface was prevented by the addition of p60 AGE-receptor. These results suggest that the interaction of AGE-modified proteins with the membrane-bound AGE-receptor may play an important role in the pathogenesis of diabetic retinopathy.

  19. 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

  20. An effective programme to systematic diabetic retinopathy screening in order to reduce diabetic retinopathy blindness.

    PubMed

    Papavasileiou, Evangelia; Dereklis, Dimitrios; Oikonomidis, Panayiotis; Grixti, Andre; Vineeth Kumar, Balakrishna; Prasad, Som

    2014-01-01

    The number of people identified with diabetes in England increased by nearly 5% during 2011-2012 to well over 2.5 million. During 2011-2012 the NHS Diabetic Eye Screening Programme screened more than 1.9 million people. In general, the UK is doing very well with its DR screening targets. It is a world leader in diabetic retinopathy screening, having offered 85.7% of eligible diabetic patients the screening programme. However, the target is 100% and efforts are still being made to improve screening locally. Our aim is to evaluate the prevalence of sight-threatening diabetic retinopathy (STDR) (proliferative retinopathy or maculopathy), the number of patients needing laser treatment or vitrectomy and registered blind in the last 12 months in a defined population. We did a twelve-month retrospective database review at the Systematic Diabetic Retinopathy Screening Service at Wirral University Hospital Trust, United Kingdom. The effectiveness of different screening modalities has been widely investigated. UK studies show sensitivity levels for the detection of sight-threatening diabetic retinopathy of 41%-67% for general practitioners, 48%-82% for optometrists, 65% for ophthalmologists, and 27%-67% for diabetologists and hospital physicians using direct ophthalmoscopy. Sensitivity for the detection of referable retinopathy by optometrists have been found to be 77%-100%, with specificity of 94%-100%. Photographic methods currently use digital images with subsequent grading by trained individuals. Sensitivity for the detection of sight-threatening diabetic retinopathy have been found 87%-100% for a variety of trained personnel reading mydriatic 45° retinal photographs, with specificities of 83%-96%. The British Diabetic Association (Diabetes UK) has established standard values for any diabetic retinopathy screening programme of at least 80% sensitivity and 95% specificity. We used descriptive analyses to characterise the study population and patterns of diabetic

  1. Neurodegeneration and Neuroprotection in Diabetic Retinopathy

    PubMed Central

    Ola, Mohammad Shamsul; Nawaz, Mohd Imtiaz; Khan, Haseeb A.; Alhomida, Abdullah S.

    2013-01-01

    Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide. PMID:23358247

  2. 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

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

    PubMed

    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

  4. Growth Factors in Proliferative Diabetic Retinopathy

    PubMed Central

    Khan, Zia Ali

    2003-01-01

    Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients. PMID:14668050

  5. Role of FAM18B in diabetic retinopathy

    PubMed Central

    Rao, Vidhya R.; Chen, Judy J.; Lussier, Yves A.; Rehman, Jalees; Huang, Yong; Jager, Rama D.; Grassi, Michael A.

    2014-01-01

    Purpose Genome-wide association studies have suggested an association between a previously uncharacterized gene, FAM18B, and diabetic retinopathy. This study explores the role of FAM18B in diabetic retinopathy. An improved understanding of FAM18B could yield important insights into the pathogenesis of this sight-threatening complication of diabetes mellitus. Methods Postmortem human eyes were examined with immunohistochemistry and immunofluorescence for the presence of FAM18B. Expression of FAM18B in primary human retinal microvascular endothelial cells (HRMECs) exposed to hyperglycemia, vascular endothelial growth factor (VEGF), or advanced glycation end products (AGEs) was determined with quantitative reverse-transcription PCR (qRT-PCR) and/or western blot. The role of FAM18B in regulating human retinal microvascular endothelial cell viability, migration, and endothelial tube formation was determined following RNAi-mediated knockdown of FAM18B. The presence of FAM18B was determined with qRT-PCR in CD34+/VEGFR2+ mononuclear cells isolated from a cohort of 17 diabetic subjects with and without diabetic retinopathy. Results Immunohistochemistry and immunofluorescence demonstrated the presence of FAM18B in the human retina with prominent vascular staining. Hyperglycemia, VEGF, and AGEs downregulated the expression of FAM18B in HRMECs. RNAi-mediated knockdown of FAM18B in HRMECs contributed to enhanced migration and tube formation as well as exacerbating the hyperglycemia-induced decrease in HRMEC viability. The enhanced migration, tube formation, and decrease in the viability of HRMECs as a result of FAM18B downregulation was reversed with pyrrolidine dithiocarbamate (PDTC), a specific nuclear factor-kappa B (NF-κB) inhibitor. CD34+/VEGFR2+ mononuclear cells from subjects with proliferative diabetic retinopathy demonstrated significantly reduced mRNA expression of FAM18B compared to diabetic subjects without retinopathy. Conclusions FAM18B is expressed in the retina

  6. Macular edema. A complication of diabetic retinopathy.

    PubMed

    Ferris, F L; Patz, A

    1984-05-01

    Diabetic macular edema is the leading cause of decreased vision from diabetic retinopathy. This decreased vision is caused by an increase in extracellular fluid within the retina distorting the retinal architecture and frequently taking on a pattern of cystoid macular edema. This fluid accumulates within the retina because of the breakdown of the barriers within the retinal blood vessels and possibly the pigment epithelium. Diabetic macular edema tends to be a chronic disorder. Although spontaneous recovery is not an uncommon occurrence, over one-half of diabetics with macular edema will lose two or more lines of visual acuity within two years. The most promising treatment for diabetic macular edema has been photocoagulation. It is recommended that in all patients with diabetic macular edema attempts be made to normalize elevated blood glucose, decrease elevated blood pressure, and improve cardiac or renal status. Reduction of serum lipids by diet or pharmacologic means is an unproven treatment at this time. The Early Treatment Diabetic Retinopathy Study hopefully will provide more definitive information as to whether photocoagulation is effective in various subgroups of patients with diabetic macular edema.

  7. 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

  8. Insulin, insulin analogues and diabetic retinopathy.

    PubMed

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  9. Diabetic Retinopathy and Inflammation: Novel Therapeutic Targets

    PubMed Central

    Rangasamy, Sampathkumar; McGuire, Paul G.; Das, Arup

    2012-01-01

    Most anti-vascular endothelial growth factor (VEGF) therapies in diabetic macular edema are not as robust as in proliferative diabetic retinopathy. Although the VEGF appears to be a good target in diabetic macular edema, the anti-VEGF therapies appear to be of transient benefit as the edema recurs within a few weeks, and repeated injections are necessary. There is new evidence that indicates ‘retinal inflammation’ as an important player in the pathogenesis of diabetic retinopathy. There are common sets of inflammatory cytokines that are upregulated in both the serum and vitreous and aqueous samples, in subjects with diabetic retinopathy, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. The key inflammatory events involved in the blood retinal barrier (BRB) alteration appear to be: (1) Increased expression of endothelial adhesion molecules such as ICAM1, VCAM1, PECAM-1, and P-selectin, (2) adhesion of leukocytes to the endothelium, (3) release of inflammatory chemokines, cytokines, and vascular permeability factors, (4) alteration of adherens and tight junctional proteins between the endothelial cells, and (5) infiltration of leukocytes into the neuro-retina, resulting in the alteration of the blood retinal barrier (diapedesis). VEGF inhibition itself may not achieve neutralization of other inflammatory molecules involved in the inflammatory cascade of the breakdown of the BRB. It is possible that the novel selective inhibitors of the inflammatory cascade (like angiopoietin-2, TNFα, and chemokines) may be useful therapeutic agents in the treatment of diabetic macular edema (DME), either alone or in combination with the anti-VEGF drugs. PMID:22346115

  10. Predictive factors of diabetic complications: a possible link between family history of diabetes and diabetic retinopathy

    PubMed Central

    2014-01-01

    Background The aim of this study was assessment of predictive factors of diabetic retinopathy. Methods A cross-sectional study was designed by recruiting 1228 type 2 diabetic patients from a diabetes referral clinic over a six-month period (from July to December, 2012). Diabetes risk factors, complications, laboratory results have been recorded. Results Of the 1228 diabetic patients (54% women, mean age 58.48 ± 9.94 years), prevalence of diabetes retinopathy was 26.6%. There were significant associations between retinopathy and family history of diabetes (p = 0.04), hypertension (p = 0.0001), diabetic duration (p = 0.0001), poor glycemic control (p = 0.0001) and age of onset of diabetes (p = 0.0001). However, no significant associations were found between retinopathy with dyslipidemia and obesity. In logistic regression model, poor glycemic control (p = 0.014), hypertension (p = 0.0001), duration of diabetes (p = 0.0001) and family history of diabetes (p = 0.012) independently predicted retinopathy after adjustment for age and sex. Conclusions Diabetic complications are resulting from an interaction from genes and environmental factors. A family history of diabetes is pointing toward a possible genetic and epigenetic basis for diabetic retinopathy. Our findings suggest the role of epigenetic modifications and metabolic memory in diabetic retinopathy in subjects with family history of diabetes. PMID:24860795

  11. Ultra widefield fundus imaging for diabetic retinopathy.

    PubMed

    Kiss, Szilárd; Berenberg, Thomas L

    2014-08-01

    For decades, the standard method for screening and grading severity of diabetic retinal disease has relied upon a montage of photographs using normal angle fundus cameras. With the development of ultrawide field (UWF) fundus imaging, more of the retina can be imaged with fewer pictures, less dependence on photographer skill, and, often, greater ease on the patient. Recent studies have shown comparability between traditional and UWF imaging for standard grading of diabetic retinopathy. Moreover, UWF images can detect peripheral pathology not typically seen in standard photographs, which may enlighten our understanding of disease severity and suggest new indications for treatment. PMID:24935049

  12. A Review on Recent Developments for Detection of Diabetic Retinopathy

    PubMed Central

    2016-01-01

    Diabetic retinopathy is caused by the retinal micro vasculature which may be formed as a result of diabetes mellitus. Blindness may appear as a result of unchecked and severe cases of diabetic retinopathy. Manual inspection of fundus images to check morphological changes in microaneurysms, exudates, blood vessels, hemorrhages, and macula is a very time-consuming and tedious work. It can be made easily with the help of computer-aided system and intervariability for the observer. In this paper, several techniques for detecting microaneurysms, hemorrhages, and exudates are discussed for ultimate detection of nonproliferative diabetic retinopathy. Blood vessels detection techniques are also discussed for the diagnosis of proliferative diabetic retinopathy. Furthermore, the paper elaborates a discussion on the experiments accessed by authors for the detection of diabetic retinopathy. This work will be helpful for the researchers and technical persons who want to utilize the ongoing research in this area. PMID:27777811

  13. 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.

  14. 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)

  15. 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

  16. Does the severity of diabetic retinopathy predict pregnancy outcome?

    PubMed

    Klein, B E; Klein, R; Meuer, S M; Moss, S E; Dalton, D D

    1988-01-01

    The authors sought to determine whether the severity of diabetic retinopathy is a predictor of subsequent pregnancy outcome. One hundred and seventy-nine pregnant diabetic women were evaluated in their first trimester of pregnancy. Stereoscopic color photographs of the ocular fundus were taken and graded by the Fundus Photography Reading Center. Thirty-nine women had no retinopathy, while 28 had proliferative retinopathy in the worse eye. The women's history and hospital delivery room charts were reviewed with regard to pregnancy outcome. Thirty-three pregnancies terminated with an adverse outcome. A logistic regression analysis was used to evaluate significant predictors of pregnancy outcome. Of maternal age, duration of diabetes, glycosylated hemoglobin, proteinuria, cigarette smoking status, and severity of diabetic retinopathy, only the last variable significantly predicted an adverse outcome. These data suggest that the severity of retinopathy should be considered when counseling a pregnant diabetic woman.

  17. 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.

  18. Retinopathy and microalbuminuria in type II diabetic patients

    PubMed Central

    Manaviat, Masoud R; Afkhami, Mohammad; Shoja, Mohammad R

    2004-01-01

    Background The aim of this study was to identify risk factors for the development of retinopathy and microalbuminuria and their correlation in type II diabetic patients. Methods In this cross-sectional study 590 patients suffering from diabetis type II were examined. Fundoscopy was performed by practising ophthalmologist. The ratio of urinary albumin to creatinine was assessed by clinitek 100 (Bayer corporation–USA). HbA1C, height and weight also were measured. Results The overall prevalence of retinopathy was 39.3% (232 patients), 5.4% of which showed to be prolifrative diabetic retinopathy (PDR). The diabetic retinopathy had significant inverse correlation with body mass index (BMI) (P = 0.02). HbA1C was higher in patients with PDR (mean = 10.5%) than in patients with no signs of retinopathy (mean = 9.5%) and this difference was statistically significant (P = 0.001). The prevalence of microalbuminuria was 25.9% while 14.5% of the patients revealed to have macroalbuminuria. As expected, diabetic retinopathy and renal involvement were highly positively correlated. (P = 0.001). Conclusion Microalbuminuria is associated with diabetic retinopathy in type II diabetic patients and is a reliable marker of retinopathy. PMID:15228626

  19. Retinylamine Benefits Early Diabetic Retinopathy in Mice*

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Lee, Chieh Allen; Golczak, Marcin; Muthusamy, Arivalagan; Antonetti, David A.; Veenstra, Alexander A.; Amengual, Jaume; von Lintig, Johannes; Palczewski, Krzysztof; Kern, Timothy S.

    2015-01-01

    Recent evidence suggests an important role for outer retinal cells in the pathogenesis of diabetic retinopathy (DR). Here we investigated the effect of the visual cycle inhibitor retinylamine (Ret-NH2) on the development of early DR lesions. Wild-type (WT) C57BL/6J mice (male, 2 months old when diabetes was induced) were made diabetic with streptozotocin, and some were given Ret-NH2 once per week. Lecithin-retinol acyltransferase (LRAT)-deficient mice and P23H mutant mice were similarly studied. Mice were euthanized after 2 (WT and Lrat−/−) and 8 months (WT) of study to assess vascular histopathology, accumulation of albumin, visual function, and biochemical and physiological abnormalities in the retina. Non-retinal effects of Ret-NH2 were examined in leukocytes treated in vivo. Superoxide generation and expression of inflammatory proteins were significantly increased in retinas of mice diabetic for 2 or 8 months, and the number of degenerate retinal capillaries and accumulation of albumin in neural retina were significantly increased in mice diabetic for 8 months compared with nondiabetic controls. Administration of Ret-NH2 once per week inhibited capillary degeneration and accumulation of albumin in the neural retina, significantly reducing diabetes-induced retinal superoxide and expression of inflammatory proteins. Superoxide generation also was suppressed in Lrat−/− diabetic mice. Leukocytes isolated from diabetic mice treated with Ret-NH2 caused significantly less cytotoxicity to retinal endothelial cells ex vivo than did leukocytes from control diabetics. Administration of Ret-NH2 once per week significantly inhibited the pathogenesis of lesions characteristic of early DR in diabetic mice. The visual cycle constitutes a novel target for inhibition of DR. PMID:26139608

  20. Inflammation and Pharmacological Treatment in Diabetic Retinopathy

    PubMed Central

    Kaštelan, Snježana; Tomić, Martina; Gverović Antunica, Antonela; Salopek Rabatić, Jasminka; Ljubić, Spomenka

    2013-01-01

    Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer. PMID:24288441

  1. Early diagnosis of diabetic retinopathy in primary care

    PubMed Central

    Jimenez-Baez, Maria Valeria; Barcenas-Contreras, Rodolfo; Morales Montoya, Carlos; Espinosa-Garcia, Laura Fatima

    2015-01-01

    Objective: To evaluate the impact of a strategy for early detection of diabetic retinopathy in patients with type 2 diabetes mellitus (DMT2) in Quintana Roo, México. Methods: Study transversal, observational, prospective, analytical, eight primary care units from Mexican Social Security Institute in the northern delegation of the State of Quintana Roo, Mexico were included. A program for early detection of diabetic retinopathy (DR) in adult 376,169 was designed. Were diagnosed 683 cases of type 2 diabetes, in 105 patients randomized was conducted to direct ophthalmoscopy were subjected to a secondary hospital were assigned. Will determine the degree of diabetic retinopathy and macular edema was performed. Results: In population were 55.2% female, mean age 48+11.1 years, 23.8 % had some degree of DR, 28.0% with mild non- proliferative diabetic retinopathy 48.0 % moderate 16.0% and severe and 8.0% showed proliferative diabetic retinopathy. Those over age 30 are 2.8 times more risk of developing DR, OR= 2.8; 95%CI: 0.42-18.0, and OR= 1.7; 95%CI: 1.02-2.95 women. Conclusions: The implementation of programs aimed at the early detection of debilitating conditions such as diabetic retinopathy health impact beneficiaries, effective links between primary care systems and provide second level positive health outcomes for patient diseases. PMID:26019380

  2. Plasma kallikrein-kinin system and diabetic retinopathy.

    PubMed

    Liu, Jia; Feener, Edward P

    2013-03-01

    Diabetic retinopathy (DR) occurs, to some extent, in most people with at least 20 years' duration of diabetes mellitus. The progression of DR to its sight-threatening stages is usually associated with the worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein-kinin system (KKS) is activated during vascular injury, where it mediates important functions in innate inflammation, blood flow, and coagulation. Recent findings from human vitreous proteomics and experimental studies on diabetic animal models have implicated the KKS in contributing to DR. Vitreous fluid from people with advanced stages of DR contains increased levels of plasma KKS components, including plasma kallikrein (PK), coagulation factor XII, and high-molecular-weight kininogen. Both bradykinin B1 and B2 receptor isoforms (B1R and B2R, respectively) are expressed in human retina, and retinal B1R levels are increased in diabetic rodents. The activation of the intraocular KKS induces retinal vascular permeability, vasodilation, and retinal thickening, and these responses are exacerbated in diabetic rats. Preclinical studies have shown that the administration of PK inhibitors and B1R antagonists to diabetic rats ameliorates retinal vascular hyperpermeability and inflammation. These findings suggest that components of plasma KKS are potential therapeutic targets for diabetic macular edema. PMID:23362193

  3. 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

  4. 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

  5. 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

  6. Diabetic retinopathy in Victoria, Australia: the Visual Impairment Project

    PubMed Central

    McKay, R.; McCarty, C.; Taylor, H.

    2000-01-01

    AIM—To establish the prevalence, severity, and risk factors for diabetic retinopathy in a representative sample of Victorian residents aged 40 years and older.
METHODS—A population based, cluster sampling method was used to recruit 4744 participants (86% participation rate). Nine randomly selected, suburban Melbourne clusters and four randomly selected, rural Victorian clusters were used. Participants provided a detailed medical and personal history and underwent an ocular examination including funduscopy and fundus photography. Rural participants provided a blood sample, from which the glycosylated haemoglobin percentage was measured. The diagnosis of diabetic retinopathy was based on fundus photographs from participants with self reported diabetes.
RESULTS—The prevalence of diabetic retinopathy among people with self reported diabetes was 29.1%. The prevalence of untreated, vision threatening retinopathy was 2.8%. Retinopathy was positively associated with a longer reported duration of diabetes diagnosis (p<0.01) and with higher fractions of glycosylated haemoglobin (p<0.01). Retinopathy was not significantly associated with age, ethnicity, body mass index, glaucoma, myopia or intake of alcohol, tobacco, or aspirin (all p > 0.05).
CONCLUSIONS—Most people in Victoria with proliferative diabetic retinopathy or clinically significant macular oedema have received laser treatment. There remains however, a small but important group who have not received treatment and whose vision is threatened. People with diabetes should be encouraged to maintain strict glycaemic control and to undergo regular screening to delay or prevent the development of retinopathy.

 PMID:10906093

  7. 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

  8. Diabetic retinopathy in Mexican Americans and non-Hispanic whites.

    PubMed

    Haffner, S M; Fong, D; Stern, M P; Pugh, J A; Hazuda, H P; Patterson, J K; van Heuven, W A; Klein, R

    1988-07-01

    Mexican Americans (MAs) have a threefold greater prevalence of non-insulin-dependent diabetes mellitus (NIDDM) than non-Hispanic Whites (NHWs). Because MA diabetic subjects have greater hyperglycemia and an earlier age of onset than NHW diabetic subjects, we postulated that diabetic MAs might also have more severe diabetic retinopathy. Stereoscopic retinal photographs of the seven standard fields of each eye were taken in 257 MAs and 56 NHWs with NIDDM. The photographs were read by the University of Wisconsin Fundus Photographic Reading Center and graded with standardized criteria. The MAs had a nonsignificantly increased risk of retinopathy relative to the NHWs [odds ratio (OR) = 1.71; 95% confidence interval (Cl) = (0.93, 3.17)]. The risk of severe retinopathy (proliferative or preproliferative) relative to background or no retinopathy was significantly greater in MAs than in NHWs [OR = 2.37; 95% Cl = (1.04, 5.39)]. After control by logistic regression for duration of disease, severity of hyperglycemia, age, and systolic blood pressure, MAs still had an increased risk of severe retinopathy relative to NHWs [OR = 3.18; 95% Cl = (1.32, 7.66)]. Severe retinopathy was related to duration of disease, hyperglycemia, and insulin therapy in both ethnic groups. Previously diagnosed MA diabetic subjects also had an increased prevalence of any retinopathy [OR = 2.39; 95% Cl = (1.63, 3.50)] and severe retinopathy [OR = 3.21; 95% Cl = (2.24, 4.59)] relative to previously diagnosed White diabetic subjects (n = 896) from Wisconsin.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Prolactin and vasoinhibins: Endogenous players in diabetic retinopathy.

    PubMed

    Triebel, Jakob; Macotela, Yazmín; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2011-10-01

    Diabetic retinopathy is a disease of the retinal microvasculature that develops as a complication of diabetes mellitus and constitutes a major cause of blindness in adults of all ages. Diabetic retinopathy is characterized by the loss of capillary cells leading to increased vasopermeability, ischemia, and hypoxia that trigger the excessive formation of new blood vessels in the retina. The influence of the pituitary gland in the pathophysiology of diabetic retinopathy was recognized nearly six decades ago, but the contribution of pituitary hormones to this disease remains unclear. Recent studies have shown that the pituitary hormone prolactin is proteolytically cleaved to vasoinhibins, a family of peptides with potent antivasopermeability, vasoconstrictive, and antiangiogenic actions that can protect the eye against the deleterious effects of the diabetic state. In this review, we summarize what is known about the changes in the circulating levels of prolactin and vasoinhibins during diabetes and diabetic retinopathy as well as the implications of these changes for the development and progression of the disease with particular attention to hyperprolactinemia in pregnancy and postpartum. We discuss the effects of prolactin and vasoinhibins that may impact diabetic retinopathy and suggest these hormones as important targets for therapeutic interventions. PMID:21913303

  10. 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

  11. Homocysteine serum levels in diabetic patients with non proliferative, proliferative and without retinopathy.

    PubMed

    Malaguarnera, Giulia; Gagliano, Caterina; Giordano, Maria; Salomone, Salvatore; Vacante, Marco; Bucolo, Claudio; Caraci, Filippo; Reibaldi, Michele; 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

  12. 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

  13. 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

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

    PubMed

    Pauk-Domańska, Magdalena; Walasik-Szemplińska, Dorota

    2014-03-01

    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

  15. 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

  16. 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

  17. The Vitreomacular Interface in Diabetic Retinopathy

    PubMed Central

    Agarwal, Daniel; Gelman, Rachel; Prospero Ponce, Claudia; Stevenson, William; Christoforidis, John B.

    2015-01-01

    Diabetic retinopathy (DR) is a leading health concern and a major cause of blindness. DR can be complicated by scar tissue formation, macular edema, and tractional retinal detachment. Optical coherence tomography has found that patients with DR often have diffuse retinal thickening, cystoid macular edema, posterior hyaloid traction, and tractional retinal detachment. Newer imaging techniques can even detect fine tangential folds and serous macular detachment. The interplay of the vitreous and the retina in the progression of DR involves multiple chemokine and other regulatory factors including VEGF. Understanding the cells infiltrating pathologic membranes at the vitreomacular interface has opened up the possibility of new targets for pharmacotherapy. Vitrectomies for DR remain a vital tool to help relieve tension on the macula by removing membranes, improving edema absorption, and eliminating the scaffold for new membrane formation. Newer treatments such as triamcinolone acetonide and VEGF inhibitors have become essential as a rapid way to control DR at the vitreomacular interface, improve macular edema, and reduce retinal neovascularization. These treatments alone, and in conjunction with PRP, help to prevent worsening of the VMI in patients with DR. PMID:26425349

  18. The Vitreomacular Interface in Diabetic Retinopathy.

    PubMed

    Agarwal, Daniel; Gelman, Rachel; Prospero Ponce, Claudia; Stevenson, William; Christoforidis, John B

    2015-01-01

    Diabetic retinopathy (DR) is a leading health concern and a major cause of blindness. DR can be complicated by scar tissue formation, macular edema, and tractional retinal detachment. Optical coherence tomography has found that patients with DR often have diffuse retinal thickening, cystoid macular edema, posterior hyaloid traction, and tractional retinal detachment. Newer imaging techniques can even detect fine tangential folds and serous macular detachment. The interplay of the vitreous and the retina in the progression of DR involves multiple chemokine and other regulatory factors including VEGF. Understanding the cells infiltrating pathologic membranes at the vitreomacular interface has opened up the possibility of new targets for pharmacotherapy. Vitrectomies for DR remain a vital tool to help relieve tension on the macula by removing membranes, improving edema absorption, and eliminating the scaffold for new membrane formation. Newer treatments such as triamcinolone acetonide and VEGF inhibitors have become essential as a rapid way to control DR at the vitreomacular interface, improve macular edema, and reduce retinal neovascularization. These treatments alone, and in conjunction with PRP, help to prevent worsening of the VMI in patients with DR. PMID:26425349

  19. 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

  20. Metabolic memory: mechanisms and implications for diabetic retinopathy.

    PubMed

    Zhang, Liwei; Chen, Baihua; Tang, Luosheng

    2012-06-01

    Chronic hyperglycemia of diabetes leads to microvascular complications that severely impact quality of life. Diabetic retinopathy (DR) may be the most common of these and is a leading cause of visual impairment and blindness among working age adults in developed nations. Many large-scale type 1 and type 2 diabetes clinical trials have demonstrated that early intensive glycemic control can reduce the incidence and progression of micro and macrovascular complications. On the other hand, epidemiological and prospective data have revealed that the stressors of diabetic vasculature persist beyond the point when glycemic control has been achieved. These kinds of persistent adverse effects of hyperglycemia on the development and progression of complications has been defined as "metabolic memory", and oxidative stress, advanced glycation end products and epigenetic changes have been implicated in the process. Recent studies have indicated that such "hyperglycemic memory" may also influence DR, suggesting that manipulation of hyperglycemic memory may prove a beneficial approach to prevention and treatment. This review summarizes the evidence from DR-related clinical trials and mechanistic studies to investigate the significance of metabolic memory in DR and understand its potential as a target of molecular therapeutics aimed at reversing hyperglycemic memory. PMID:22209677

  1. 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

  2. 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

  3. 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

  4. 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

  5. Transthyretin represses neovascularization in diabetic retinopathy

    PubMed Central

    Shao, Jun

    2016-01-01

    Purpose The apoptosis of human umbilical vein endothelial cells has been reportedly induced by the protein transthyretin (TTR). In human ocular tissue, TTR is generally considered to be secreted mainly by retinal pigment epithelial cells (hRPECs); however, whether TTR affects the development of neovascularization in diabetic retinopathy (DR) remains unclear. Methods Natural and simulated DR media were used to culture human retinal microvascular endothelial cells (hRECs). Hyperglycemia was simulated by increasing the glucose concentration from 5.5 mM up to 25 mM, while hypoxia was induced with 200 µM CoCl2. To understand the effects of TTR on hRECs, cell proliferation was investigated under natural and DR conditions. Overexpression of TTR, an in vitro wound-healing assay, and a tube formation assay were employed to study the repression of TTR on hRECs. Real-time fluorescence quantitative PCR (qRT-PCR) was used to study the mRNA levels of DR-related genes, such as Tie2, VEGFR1, VEGFR2, Angpt1, and Angpt2. Results The proliferation of hRECs was significantly decreased in the simulated hyperglycemic and hypoxic DR environments. The cells were further repressed by added exogenous or endogenous TTR only under hyperglycemic conditions. The in vitro migration and tube formation processes of the hRECs were inhibited with TTR; furthermore, in the hyperglycemia and hyperglycemia/hypoxia environments, the levels of Tie2 and Angpt1 mRNA were enhanced with exogenous TTR, while those of VEGFR1, VEGFR2, and Angpt1 were repressed. Conclusions In hyperglycemia, the proliferation, migration, and neovascularization of hRECs were significantly inhibited by TTR. The key genes for DR neovascularization, including Tie2, VEGFR1, VEGFR2, Angpt1, and Angpt2, were regulated by TTR. Under DR conditions, TTR significantly represses neovascularization by inhibiting the proliferation, migration and tube formation of hRECs. PMID:27746673

  6. 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

  7. Emerging trends in ocular telemedicine: the diabetic retinopathy model.

    PubMed

    Cavallerano, Jerry; Aiello, Lloyd M

    2005-01-01

    Diabetes mellitus is a leading cause of vision loss in industrialized countries. Diabetic retinopathy has features which make it ideal for disease management by telemedicine. The American Telemedicine Association (ATA) has recently established consensus recommendations for ocular telemedicine for diabetic retinopathy, in cooperation with the US National Institute of Standards and Technology. The guiding principle is that it would be inappropriate to use telemedicine to provide anything less than the accepted standard of clinical care. The ATA practice recommendations delineate performance standards for the clinical, technical and administrative elements of ocular telemedicine for diabetic retinopathy. Four clinical categories of assessment were identified. Category 4 validation, for example, indicates that a system matches or exceeds the ability of current photographs to identify lesions of diabetic retinopathy. To create the practice recommendations, workshops were held to address each of the three components: (1) clinical, (2) technical, and (3) operational and business. Ocular telemedicine programmes will need to demonstrate sustainability and cost-effectiveness, and respect a patient's right to privacy. Nevertheless, ocular telemedicine seems poised to become an integral part of eye health care, as long as programmes meet or exceed present clinical standards of care, and patient and provider expectations are clearly defined.

  8. The role lipid aldehydes and ALEs in the pathogenesis of diabetic retinopathy.

    PubMed

    Curtis, Tim

    2014-10-01

    Diabetic retinopathy is one of the most common causes of blindness in people of working age in developed countries. The retinal vasculature is central to the development of diabetic retinopathy, but there is accumulating evidence that neuroretinal dysfunction and degeneration also contributes to the aetiology and progression of this disease. The precise mechanisms through which diabetes causes neuroretinal dysfunction and degeneration remain to be fully established, but recent evidence from our own group has suggested that lipid aldehyde generation and the formation of advanced lipoxidation end-products (ALEs) plays a key contributory role. In the present talk, I will outline our recent data suggesting that the progressive and selective accumulation of the acrolein-derived ALE, FDP-lysine, in retinal Müller glial cells during diabetes is involved in the pathogenesis of neuroretinal dysfunction during diabetic retinopathy. More recent unpublished data will also be presented suggesting that FDP-lysine accumulation in the diabetic retina may occur primarily through a mechanism involving the downregulation of aldehyde detoxification enzymes. Current studies examining potential therapeutic strategies for preventing ALE accumulation in the diabetic retina will also be briefly discussed.

  9. Ophthalmoscopy versus fundus photographs for detecting and grading diabetic retinopathy.

    PubMed

    Kinyoun, J L; Martin, D C; Fujimoto, W Y; Leonetti, D L

    1992-05-01

    Reported here is the agreement between three examination methods chosen to detect and grade diabetic retinopathy in 124 subjects with type II (noninsulin-dependent) diabetes mellitus. These three examination methods include ophthalmoscopy (indirect and direct) by a retina specialist, seven standard field fundus photographs read by the same retina specialist, and the same photographs read by a trained photographic grader at the Fundus Photograph Reading Center. For the 59 subjects examined with all three methods, these results indicated fair to good (kappas, 0.69-0.84) agreement between the retina specialist's and trained grader's reading of photographs, fair to good (kappas, 0.58-0.79) agreement between the retina specialist's ophthalmoscopic findings and the specialist's reading of photographs, and fair (kappas, 0.49-0.62) agreement between the retina specialist's ophthalmoscopic findings and the trained grader's reading of fundus photographs. Analysis of the disagreements confirmed earlier reports that ophthalmoscopy misses approximately 50% of eyes with microaneurysms only. Other disagreements resulted from the trained grader's overreading photographs of eyes with lesions simulating diabetic retinopathy. Of the 393 total subjects (diabetic and nondiabetic) in this study, such lesions were seen with ophthalmoscopy in six eyes of six subjects (2.4% of diabetic patients and 1.1% of nondiabetic subjects). The authors believe at least one definite retinal microaneurysm should be present in one eye before establishing the diagnosis of diabetic retinopathy in diabetic patients.

  10. GLP-1 agonist treatment: implications for diabetic retinopathy screening.

    PubMed

    Varadhan, Lakshminarayanan; Humphreys, Tracy; Hariman, Christian; Walker, Adrian B; Varughese, George I

    2011-12-01

    Rapid improvement in glycaemic control induced by GLP-1 agonist therapy could be yet another illustration of transient or permanent progression of diabetic retinopathy, similar to documented examples such as pregnancy and continuous subcutaneous insulin infusion. Specific guidelines would be needed to monitor this paradoxical phenomenon during treatment with GLP-1 agonists. PMID:21906831

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

    PubMed

    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.

  12. 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

  13. 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

  14. The Medical Check-Up for Potentially Serious Diabetic Retinopathy

    PubMed Central

    Begg, Iain S.

    1986-01-01

    In developed countries diabetic retinopathy is a major cause of visual impairment and the leading cause of blindness in the population aged 20-65 years. Serious retinopathy has a presymptomatic phase which underscores the importance of ophthalmoscopy in screening patients to detect microvascular abnormalities that are early and late predictors of increasing severity. The diagnosis of “high risk characteristics” for visual loss and “clinically significant macular edema” is essential, as photocoagulation treatment has been shown conclusively to reduce the rate of blindness and slow the rate of progression of retinopathy. The complete medical check-up and early referral for diagnostic work-up should lead to less disability. ImagesFigure 2Figure 3Figure 4Figure 5 PMID:21267098

  15. 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

  16. 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

  17. Novel Diabetic Mouse Models as Tools for Investigating Diabetic Retinopathy

    PubMed Central

    Kador, Peter F.; Zhang, Peng; Makita, Jun; Zhang, Zifeng; Guo, Changmei; Randazzo, James; Kawada, Hiroyoshi; Haider, Neena; Blessing, Karen

    2012-01-01

    Objective Mouse models possessing green fluorescent protein (GFP) and/or human aldose reductase (hAR) in vascular tissues have been established and crossed with naturally diabetic Akita mice to produce new diabetic mouse models. Research Design and Methods Colonies of transgenic C57BL mice expressing GFP (SMAA-GFP), hAR (SMAA-hAR) or both (SMAA-GFP-hAR) in vascular tissues expressing smooth muscle actin were established and crossbred with C57BL/6-Ins2Akita/J (AK) mice to produce naturally diabetic offspring AK-SMAA-GFP and AK-SMAA-GFP-hAR. Aldose reductase inhibitor AL1576 (ARI) was administered in chow. Retinal and lenticular sorbitol levels were determined by HPLC. Retinal functions were evaluated by electroretinography (ERGs). Growth factor and signaling changes were determined by Western Blots using commercially available antibodies. Retinal vasculatures were isolated from the neural retina by enzymatic digestion. Flat mounts were stained with PAS-hematoxylin and analyzed. Results Akita transgenics developed DM by 8 weeks of age with blood glucose levels higher in males than females. Sorbitol levels were higher in neural retinas of AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice also had higher VEGF levels and reduced ERG scotopic b-wave function, both of which were normalized by AL1576. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors bFGF, IGF-1, and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK and P-44/42 MAPK that were also reduced by ARI treatment. Quantitative analysis of flat mounts in 18 week AK-SMAA-GFP-hAR mice revealed increased loss of nuclei/capillary length and a significant increase in the percentage of acellular capillaries present which was not seen in AK-SMAA-GFP-hAR treated with ARI. Conclusions/Significance These new mouse models of early onset diabetes may be valuable tools for assessing both the role of hyperglycemia and AR in the development of retinal lesions associated with diabetic

  18. Raman spectroscopy characterization of diabetes effects on human vitreous in diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Sebag, Jerry; Nie, Shuming; Reiser, Karen M.; Yu, Nai-Teng

    1993-06-01

    Nonenzymatic glycation alters collagen throughout the body, resulting in the histopathology that underlies diabetic disease in several organs. In the eye such changes in vitreous collagen could contribute to the progression of proliferative diabetic retinopathy by inducing vitreous degeneration. In this study, near infrared Fourier-transform Raman spectroscopy was performed on vitreous obtained at surgery from diabetic patients and from non-diabetic control subjects. The findings were compared to measurements obtained in untreated and glycated (in vitro) rat-tail tendon collagen, as well as demineralized chick bone, rich in crosslinks. The results demonstrated substantial changes in diabetic vitreous collagen not resulting from enzyme-mediated crosslinking, but most likely advanced nonenzymatic glycation. This approach appears to be useful as a means of characterizing the molecular changes induced by diabetes. Furthermore, this technique could be developed as a way of quantifying these changes in vivo in several tissues, so as to gauge the severity of disease and monitor the response to therapy.

  19. SYSTEMIC INTERLEUKIN 1β INHIBITION IN PROLIFERATIVE DIABETIC RETINOPATHY

    PubMed Central

    Stahel, Marc; Becker, Matthias; Graf, Nicole

    2016-01-01

    Purpose: To evaluate the effect of systemic interleukin 1β inhibition using canakinumab (Ilaris) on retinal neovascularizations in proliferative diabetic retinopathy. Methods: Patients with proliferative diabetic retinopathy were enrolled in a prospective uncontrolled pilot study. Canakinumab (150 mg) was given 3 times subcutaneously. The primary end point was the change in the area of neovascularization from baseline to Week 24. Secondary end points were the change in retinal edema measured and best-corrected visual acuity (BCVA), as well as systemic safety evaluation, HbA1c, and systemic inflammatory parameters. Results: Systemic canakinumab treatment was well tolerated. None of the 8 eyes showed progression of neovascularizations within 24 weeks. Their mean size remained unchanged comparing 0.60 mm2 at baseline with 0.62 mm2 at Week 24 (P = 0.944). Median BCVA remained stable with 80 ETDRS letters at baseline and 82 ETDRS letters at Week 24. A not statistically significant reduction in retinal edema was detectable for the foveal central subfield thickness (mean, 313–295 μm). Mean HbA1c improved significantly from 7.92% to 7.30% within the 24 weeks (P = 0.046). Systemic inflammatory parameters remained overall unchanged. Conclusion: Systemic canakinumab showed no change in neovascularizations in diabetic retinopathy. Promising effects were seen on diabetic macular edema. PMID:26218500

  20. Vitamin D Deficiency Is Not Associated with Diabetic Retinopathy or Maculopathy

    PubMed Central

    Alam, Uazman; Amjad, Yasar; Chan, Anges Wan Shan; Asghar, Omar; Petropoulos, Ioannis N.; Malik, Rayaz A.

    2016-01-01

    Background. Experimental and clinical studies suggest a possible association between vitamin D deficiency and both diabetic retinopathy and maculopathy. Methods. We have performed a cross-sectional study in adults with types 1 and 2 diabetes mellitus. The relationship between the presence and severity of diabetic retinopathy and maculopathy with serum 25-hydroxyvitamin D concentration was evaluated using logistic regression analyses in the presence of demographic and clinical covariates. Results. 657 adults with diabetes were stratified based on retinopathy grading: No Diabetic Retinopathy (39%), Background Diabetic Retinopathy (37%), Preproliferative Diabetic Retinopathy (21%), and Proliferative Diabetic Retinopathy (3%), respectively. There were no differences in serum 25-hydroxyvitamin D concentrations (25(OH)D) between the groups (15.3 ± 9.0 versus 16.4 ± 10.5 versus 15.9 ± 10.4 versus 15.7 ± 8.5 ng/mL, P = NS). Logistic regression analysis demonstrated no statistically significant relationship between the severity of retinopathy and serum 25(OH)D. Furthermore, there was no difference in serum 25(OH)D between those with (n = 94, 14%) and those without (n = 563, 86%) Diabetic Maculopathy (16.2 ± 10.0 versus 15.8 ± 9.8, P = NS) and no relationship was demonstrated by logistic regression analyses between the two variables. Conclusions. This study has found no association between serum 25(OH)D and the presence and severity of diabetic retinopathy or maculopathy. PMID:26885530

  1. 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

  2. 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

  3. Neurodegeneration is an early event in diabetic retinopathy: therapeutic implications.

    PubMed

    Simó, Rafael; Hernández, Cristina

    2012-10-01

    Diabetic retinopathy (DR) remains the leading cause of blindness among working-age individuals in developed countries. Current treatments for DR are indicated in advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of DR are needed. DR has been classically considered to be a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the underlying mechanisms that lead to neurodegeneration will be essential for identifying new therapeutic targets. From the clinical point of view, the identification of those patients in whom retinal neurodegeneration appears will be crucial for implementing early treatment based on neuroprotective drugs. When the early stages of DR are the therapeutic target, it would be inconceivable to recommend an aggressive treatment such as intravitreous injections. By contrast, topical administration of neuroprotective drugs by using eye drops is a possible option. However, clinical trials to determine the safety and effectiveness of this non-invasive route, as well as a standardisation of the methods for monitoring neurodegeneration, are needed. PMID:22887976

  4. Challenges in elucidating the genetics of diabetic retinopathy

    PubMed Central

    Kuo, Jane Z.; Wong, Tien Y.; Rotter, Jerome I.

    2014-01-01

    Importance In the past decade, significant progress in genomic medicine and technological advances have revolutionized our approach to common complex disorders in many areas of medicine, including ophthalmology. A major disorder that still needs major genetic progress is diabetic retinopathy (DR), one of the leading causes of blindness in adults. Objective To perform a literature review, present the current findings, and highlight some key challenges. Methods Thorough literature review of the genetic factors for DR, including heritability scores, twin studies, family studies, candidate gene studies, linkage studies, and genome-wide association studies (GWAS). Results While there is clear demonstration of a genetic contribution in the development and progression of DR, the identification of susceptibility loci through candidate gene approaches, linkage studies, and GWAS is still in its infancy. The greatest obstacles remain a lack of power due to small sample size of available studies and a lack of phenotype standardization. In this review, we also discuss novel technologies and novel approaches, such as intermediate phenotypes for biomarkers, proteomics, metabolomics, exome chips, and next-generation sequencing that may facilitate future studies of DR. Conclusions and Relevance The field of the genetics of DR is still in its infancy and is a challenge due to the complexity of the disease itself. This review outlines some strategies and lessons for future investigation to improve our understanding of this most complex of genetic disorders. PMID:24201651

  5. [Interdisciplinary interaction in vascular diseases of the eye, diabetes and diabetic retinopathy].

    PubMed

    Kleophas, W; Dellanna, F

    2014-01-01

    The incidence of diabetes mellitus type 2 is greatly increasing worldwide. An early therapy with intensified control of diabetes and blood pressure is especially important to avoid delayed complications. In addition to diabetic foot syndrome, diabetic retinopathy and diabetic nephropathy still represent commonly occurring problems. Despite improvements in the quality of care, the targets of the St. Vincent Declaration have still not yet been achieved. Diabetic retinopathy and diabetic nephropathy show parallels in the course of the disease and in the pathological anatomical alterations which have led to the inauguration of a diabetic renal-retinal syndrome. The ophthalmological assessment of the retina was previously considered to be a diagnostic aid for assessment of diabetic nephropathy; however, nowadays a simple estimation of the glomerular filtration rate using the modification of diet in renal disease (MDRD) formula and determination of microalbuminuria can in contrast give ophthalmologists an early indication of the possible presence of microangiopathic alterations.

  6. 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.

  7. 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.

  8. 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.

  9. Colour Doppler ultrasound evaluation of orbital vessels in diabetic retinopathy.

    PubMed

    Baydar, S; Adapinar, B; Kebapci, N; Bal, C; Topbas, S

    2007-06-01

    The aim of this study was to determine the role of colour Doppler imaging in the retrobulbar vascular circulation in diabetic retinopathy (DR). Maximum (V(max)), end-diastolic (V(min)) and average (V(mean)) velocities of blood flows and pulsatility index and resistivity index (RI) in central retinal artery (CRA), short branches of posterior ciliary artery (PCA) and ophthalmic artery of the 65 diabetic and 22 control eyes were measured. The CRA V(max) level in the control group was significantly higher than in DR groups. The CRA V(mean) level was also significantly higher in the control group than in the mild nonproliferative diabetic retinopathy (NPDR) and the moderate NPDR groups. The CRA RI value was significantly higher in the control group than in the nonretinopathy group. The CRA V(min) and the ophthalmic artery RI values were found significantly higher in the nonretinopathy group than in the moderate NPDR group. There were significant decreases in the some CRA and PCA values as glycated haemoglobin (HbA1c) levels increase in diabetic group. There was a positive correlation between the duration of diabetes and HbA1c levels. This study showed the presence of some dynamic circulatory alterations in the nonretinopathy group with diabetes and DR groups. It was also shown that there is a negative correlation between HbA1c and some orbital vascular velocities.

  10. 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

  11. 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.

  12. Diabetic Retinopathy in Pregnancy: A Population-Based Study of Women with Pregestational Diabetes

    PubMed Central

    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

  13. Molecular Mechanisms of Diabetic Retinopathy: Potential Therapeutic Targets

    PubMed Central

    Coucha, Maha; Elshaer, Sally L.; Eldahshan, Wael S.; Mysona, Barbara A.; El-Remessy, Azza B.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults in United States. Research indicates an association between oxidative stress and the development of diabetes complications. However, clinical trials with general antioxidants have failed to prove effective in diabetic patients. Mounting evidence from experimental studies that continue to elucidate the damaging effects of oxidative stress and inflammation in both vascular and neural retina suggest its critical role in the pathogenesis of DR. This review will outline the current management of DR as well as present potential experimental therapeutic interventions, focusing on molecules that link oxidative stress to inflammation to provide potential therapeutic targets for treatment or prevention of DR. Understanding the biochemical changes and the molecular events under diabetic conditions could provide new effective therapeutic tools to combat the disease. PMID:25949069

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

    PubMed Central

    Ljubimov, Alexander V

    2015-01-01

    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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. [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

  20. [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.

  1. Telemedicine in Diabetic Retinopathy: Current Status and Future Directions

    PubMed Central

    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

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

    PubMed

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

    2015-06-10

    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.

  3. Automatic detection of retinal anatomy to assist diabetic retinopathy screening.

    PubMed

    Fleming, Alan D; Goatman, Keith A; Philip, Sam; Olson, John A; Sharp, Peter F

    2007-01-21

    Screening programmes for diabetic retinopathy are being introduced in the United Kingdom and elsewhere. These require large numbers of retinal images to be manually graded for the presence of disease. Automation of image grading would have a number of benefits. However, an important prerequisite for automation is the accurate location of the main anatomical features in the image, notably the optic disc and the fovea. The locations of these features are necessary so that lesion significance, image field of view and image clarity can be assessed. This paper describes methods for the robust location of the optic disc and fovea. The elliptical form of the major retinal blood vessels is used to obtain approximate locations, which are refined based on the circular edge of the optic disc and the local darkening at the fovea. The methods have been tested on 1056 sequential images from a retinal screening programme. Positional accuracy was better than 0.5 of a disc diameter in 98.4% of cases for optic disc location, and in 96.5% of cases for fovea location. The methods are sufficiently accurate to form an important and effective component of an automated image grading system for diabetic retinopathy screening.

  4. [Modern trends in the treatment of diabetic retinopathy (author's transl)].

    PubMed

    Freyler, H

    1977-02-10

    Adequate control of diabetic patients may not only delay the appearance of diabetic retinopathy, but may, moreover, effect the regression of fundus changes at the pre-retinopathic stage and in cases of commencing non-proliferative retinopathy. Medical treatment is based on the achievement of a decrease in vascular permeability and a lowering of the blood lipid level; a diet enriched with phosphates may influence retinal hypoxia by increasing the 2,3 diphosphoglycerate level in the erythrocytes, thereby leading to an improved free oxygen supply to the tissue. Complete medical and dietetic compensation of hyper-permeability of the retinal capillaries, of the intraretinal exudation of lipoproteins, and of retinal hypoxia belong still today to utopia; hence, conservative treatment is only of auxiliary character. Hypophysectomy has largely been abandoned in view of the mutilation involved and the poor results of this procedure. The most effective active treatment is photocoagulation. The best results are obtained by a combination of generalized unselective coagulation of the peripheral retina by means of a xenon coagulator and the selective elimination of progressive vascular changes seen in the fluorescein angiogram with argon laser.

  5. Anterior Diabetic Retinopathy Studied by Ultra-widefield Angiography

    PubMed Central

    Bae, Kunho; Lee, Ju Yeon; Kim, Tae Hyup; Cho, Ga Eun; Ahn, Jeeyun; Kim, Sang Jin; Kim, Jae Hyun

    2016-01-01

    Purpose To evaluate the prevalence of anterior type diabetic retinopathy (DR) using ultra-widefield fluorescein angiography and to identify the factors associated with anterior type DR incidence. Methods A retrospective case review was used in this study. Patients with non-proliferative diabetic retinopathy (NPDR) underwent examination by ultra-widefield fluorescein angiography, and were classified into anterior, posterior, or diffuse DR groups. Anterior DR was defined if diabetic retinal changes were noted only at the location anterior to the imaginary circle bordered by the Early Treatment Diabetic Retinopathy Study seven-standard fields. Correlations between demographic data, as well as systemic and ocular factors, and the incidence of NPDR types were evaluated. Results Among the 234 eyes of 234 patients with NPDR, 25 eyes (10.7%) demonstrated anterior DR. Anterior DR was observed in 10 eyes (30.3%) of patients having mild NPDR, three eyes (4.8%) of moderate NPDR patients, and in 12 eyes (7.1%) of severe NPDR patients (p < 0.001). The incidence of anterior DR positively correlated with lower hemoglobin A1c levels and with greater high-density lipoprotein levels following multiple logistic regression analysis (p < 0.001). The mean hemoglobin A1c level was 7.03 ± 0.99% in anterior DR, 7.99 ± 1.74% in posterior DR, and 7.94 ± 1.39% in diffuse DR patients (p = 0.003). The mean high-density lipoprotein level was 51.2 ± 12.5 mg/dL in anterior, 49.7 ± 15.2 mg/dL in posterior, and 45.2 ± 13.1 mg/dL in diffuse DR patients (p = 0.010). Conclusions Diabetic retinal changes confined to an anterior location were more frequently noted in earlier stages of NPDR. The incidence of DR sparing posterior retinal involvement was related to favorable blood sugar and lipid profiles. PMID:27729754

  6. Glycaemic threshold for diabetes-specific retinopathy among individuals from Saudi Arabia, Algeria and Portugal.

    PubMed

    Almdal, T P; Handlos, L N; Valerius, M; Juul, E; Nielsen, K E; Vistisen, D; Nielsen, L B; Sheikh, A; Belhadj, M; Nadir, D; Zinai, S; Raposo, J; Lund-Andersen, H; Witte, D R

    2014-03-01

    We studied the glycaemic threshold and prevalence of diabetic retinopathy in screen-detected diabetes in Saudi Arabia, Algeria and Portugal. The prevalence of diabetes-specific retinopathy started to increase at an HbA1c level of 6-6.4% (42-47 mmol/mol) and in individuals with HbA(1c) >7.0% the prevalence was 6.0%.

  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. [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

  9. 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

  10. Protective Effects of Fufang Xueshuantong on Diabetic Retinopathy in Rats

    PubMed Central

    Duan, Huihui; Huang, Jianmei; Li, Wei; Tang, Minke

    2013-01-01

    The aim of this study was to evaluate the protective effects of Fufang Xueshuantong (FXT) on diabetic retinopathy in rats induced by streptozotocin (STZ). Diabetes was induced in Sprague-Dawley rats by a single injection of 60 mg/kg STZ. One week after STZ, FXT 0.525 g/kg or 1.05 g/kg was administrated to the rats by intragastric gavage (ig) once daily consecutively for 24 weeks. The control rats and untreated STZ rats received vehicle the same way. At the end of the experiment, the erythrocyte aggregation and blood viscosity were assayed. The retina vessel morphology was observed in retinal digestive preparations. Expression of occludin and intercellular adhesion molecule-1 (ICAM-1) in retina was measured by western blotting. Expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in retina was detected by immunohistochemistry. The activity of aldose reductase in retina was investigated with a NADPH oxidation method. The results showed that, in STZ rats, there were distinct lesions in retinal vessel, including decrease of pericytes and increase of acellular capillaries, together with dilatation of retinal veins. The expression of VEGF and ICAM-1 increased, while the expression of PEDF and occludin decreased. The activity of aldose reductase elevated, and the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also increased after STZ stimulation. FXT 0.525 g/kg and 1.05 g/kg demonstrated significant protective effects against STZ induced microvessel lesion in the retina with increased pericytes and reduced acellular capillaries. FXT also reduced the expression of VEGF and ICAM-1 and enhanced the expression of PEDF and occludin in STZ insulted rats. The activity of aldose reductase, the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also decreased after FXT treatment. The results demonstrated that FXT has protective effect on STZ induced diabetic retinopathy in rats. PMID

  11. 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

  12. [Retinopathy and angiopathy in diabetes of fifty to sixty years duration (author's transl)].

    PubMed

    Fischer, F

    1977-11-01

    A report is given on ten (seven female, three male) diabetis with uncommonly long duration of the disease. Diabetes had become manifest at an early age (mostly childhood) and, then, had continued for a period of fifty to sixty-one years. Eight patients suffer from retinopathy, two are free from it. Only three cases show nephropathy of moderate development and inconspicuous progression. Coronary sclerosis, peripheral sclerosis, and neuropathy recede with time. There is a surprising discrepancy of findings concerning retinopathy - on the one hand: simple retinopathy tending to spontaneous regression; on the other hand: malignant proliferating retinopathy. Uncommon also is the tarrying behaviour of nephropathy.

  13. 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

  14. Update on animal models of diabetic retinopathy: from molecular approaches to mice and higher mammals

    PubMed Central

    Robinson, Remya; Barathi, Veluchamy A.; Chaurasia, Shyam S.; Wong, Tien Y.; Kern, Timothy S.

    2012-01-01

    Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the major causes of blindness worldwide. The pathogenesis of DR has been investigated using several animal models of diabetes. These models have been generated by pharmacological induction, feeding a galactose diet, and spontaneously by selective inbreeding or genetic modification. Among the available animal models, rodents have been studied most extensively owing to their short generation time and the inherited hyperglycemia and/or obesity that affect certain strains. In particular, mice have proven useful for studying DR and evaluating novel therapies because of their amenability to genetic manipulation. Mouse models suitable for replicating the early, non-proliferative stages of the retinopathy have been characterized, but no animal model has yet been found to demonstrate all of the vascular and neural complications that are associated with the advanced, proliferative stages of DR that occur in humans. In this review, we summarize commonly used animal models of DR, and briefly outline the in vivo imaging techniques used for characterization of DR in these models. Through highlighting the ocular pathological findings, clinical implications, advantages and disadvantages of these models, we provide essential information for planning experimental studies of DR that will lead to new strategies for its prevention and treatment. PMID:22730475

  15. 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

  16. 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

  17. 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

  18. 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.

  19. [Management pattern of diabetes mellitus and prevention and control of diabetic retinopathy].

    PubMed

    Hui, Yan-nian

    2010-02-01

    The Bureau of Disease Prevention and Control, National Ministry of Health, recently released a project for the management of diabetes mellitus along with a technical operational manual. This is a landmark event in the prevention and management of ocular fundus diseases in China. This project will be carried out through collaboration of general hospitals, community health service units, and disease prevention and control organizations. It provides an excellent platform for the prevention and control of diabetic retinopathy. In order to prevent and control this disease, we should follow the patient-centered principle, which includes establishing individual health files, providing consultation for patients, performing screening of diabetic retinopathy, and providing lifelong regular examinations, follow-up and prompt treatments. We should also insist on the combination of prevention, treatment and scientific study to take advantage of a wide array of population resources for studying the pathogenesis and risk factors involved in the development of diabetic retinopathy, and making new contributions in the prevention of blindness due to diabetes.

  20. The retinal renin-angiotensin system: implications for therapy in diabetic retinopathy.

    PubMed

    Sjølie, A K; Chaturvedi, N

    2002-08-01

    Retinopathy is the most common complication of diabetes, and a leading cause of blindness in people of working age. Optimal blood pressure and metabolic control can reduce the risk of diabetic retinopathy, but are difficult to achieve in clinical practice. In the EUCLID Study, the angiotensin converting enzyme (ACE) inhibitor lisinopril reduced the risk of progression of retinopathy by approximately 50%, and also significantly reduced the risk of progression to proliferative retinopathy. These findings are consistent with extensive evidence that the renin-angiotensin system is expressed in the eye, and that adverse effects of angiotensin II on retinal angiogenesis and function can be inhibited by ACE inhibitors or angiotensin II-receptor blockers. However, in the EUCLID Study retinopathy was not a primary end-point and the study was not sufficiently powered for the eye-related outcomes. Hence, the Diabetic Retinopathy Candesartan Trials (DIRECT) programme has been established to determine whether AT(1)-receptor blockade with candesartan can prevent the incidence and progression of diabetic retinopathy. This programme comprises three studies, involving a total of 4500 patients recruited from about 300 centres worldwide. The patients are normotensive or treated hypertensive individuals, and so the DIRECT programme should assess the potential of an AT(1)-receptor blocker to protect against the pathological changes in the eye following diabetes.

  1. The retinal renin-angiotensin system: implications for therapy in diabetic retinopathy.

    PubMed

    Sjølie, A K; Chaturvedi, N

    2002-08-01

    Retinopathy is the most common complication of diabetes, and a leading cause of blindness in people of working age. Optimal blood pressure and metabolic control can reduce the risk of diabetic retinopathy, but are difficult to achieve in clinical practice. In the EUCLID Study, the angiotensin converting enzyme (ACE) inhibitor lisinopril reduced the risk of progression of retinopathy by approximately 50%, and also significantly reduced the risk of progression to proliferative retinopathy. These findings are consistent with extensive evidence that the renin-angiotensin system is expressed in the eye, and that adverse effects of angiotensin II on retinal angiogenesis and function can be inhibited by ACE inhibitors or angiotensin II-receptor blockers. However, in the EUCLID Study retinopathy was not a primary end-point and the study was not sufficiently powered for the eye-related outcomes. Hence, the Diabetic Retinopathy Candesartan Trials (DIRECT) programme has been established to determine whether AT(1)-receptor blockade with candesartan can prevent the incidence and progression of diabetic retinopathy. This programme comprises three studies, involving a total of 4500 patients recruited from about 300 centres worldwide. The patients are normotensive or treated hypertensive individuals, and so the DIRECT programme should assess the potential of an AT(1)-receptor blocker to protect against the pathological changes in the eye following diabetes. PMID:12140727

  2. Corneal Confocal Microscopy Detects Neuropathy in Patients with Type 1 Diabetes without Retinopathy or Microalbuminuria

    PubMed Central

    Chan, Agnes W. S.; Alam, Uazman; Fadavi, Hassan; Marshall, Andrew; Asghar, Omar; Efron, Nathan; Tavakoli, Mitra; Malik, Rayaz A.

    2015-01-01

    Objective Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria. Materials and Methods All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)]. Results 53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria. Conclusions IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes. PMID:25853247

  3. Neurotrophins and Neurotrophin Receptors in Proliferative Diabetic Retinopathy

    PubMed Central

    Abu El-Asrar, Ahmed M.; Mohammad, Ghulam; De Hertogh, Gert; Nawaz, Mohd Imtiaz; Van Den Eynde, Kathleen; Siddiquei, Mohammad Mairaj; Struyf, Sofie; Opdenakker, Ghislain; Geboes, Karel

    2013-01-01

    Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR. PMID:23762379

  4. Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.

    PubMed

    Abu El-Asrar, Ahmed M; Mohammad, Ghulam; De Hertogh, Gert; Nawaz, Mohd Imtiaz; Van Den Eynde, Kathleen; Siddiquei, Mohammad Mairaj; Struyf, Sofie; Opdenakker, Ghislain; Geboes, Karel

    2013-01-01

    Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR. PMID:23762379

  5. Vascular endothelial growth factor-A: a multifunctional molecular player in diabetic retinopathy.

    PubMed

    Zhang, Xinyuan; Bao, Shisan; Hambly, Brett D; Gillies, Mark C

    2009-12-01

    Vascular endothelial growth factor-A (VEGF-A), first described as "vascular permeability factor", is a critical molecule in the pathogenesis of diabetic retinopathy at several levels. Previous studies have outlined the importance of VEGF-A in mediating vascular pathology in both experimental models and clinical diabetic retinopathy, which are characterized by retinal vascular leakage, preretinal neovascularisation and neuronal degeneration. Paradoxically, recent reports have emphasized the potential neurotrophic effects of VEGF-A on the quiescent vasculature, as well as its direct and indirect protective effects on retinal neurons. VEGF-A has also been identified as an important signalling regulator in the normal central nervous system. Consequently, anti-VEGF therapy for diabetic retinopathy has become a controversal issue. This review outlines recently developed concepts relating to the role of VEGF-A in the pathogenesis of diabetic retinopathy, with particular emphasis on its implications for clinical practice. PMID:19646547

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Cannabidiol As a Putative Novel Therapy for Diabetic Retinopathy: A Postulated Mechanism of Action as an Entry Point for Biomarker-Guided Clinical Development.

    PubMed

    Liou, Gi; El-Remessy, Ab; Ibrahim, As; Caldwell, Rb; Khalifa, Ym; Gunes, A; Nussbaum, Jj

    2009-09-01

    Diabetic retinopathy is a leading cause of blindness in the Western world. However, treatment options for diabetic retinopathy are limited and display poor efficacy with marked patient-to-patient variation in therapeutic outcomes. Discovery of new molecular entities acting on mechanistically novel biological pathways remains as one of the key research priorities in diabetic retinopathy. Moreover, given the variable success of the existing treatment modalities, a targeted and personalized drug development strategy could be more fruitful for rational and successful transition of preclinical discoveries to the clinical realm. This review is focused on cannabidiol, a non-psychoactive native cannabinoid, as an emerging and novel therapeutic modality based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy - one of the retinal diseases associated with vascular neuroinflammation. We present the postulated and preclinically documented novel mechanisms that may underlie cannabidiol mode of action in diabetic retinopathy. We discuss the interindividual variation in pharmacokinetic pathways as well as in the SLC29A1 gene, a molecular target for cannabidiol. We emphasize that the novel mode of action of cannabidiol and the previous failures with nontargeted interventions in diabetic retinopathy collectively demand a more rational and personalized clinical development strategy for compounds that have shown promise at the preclinical stage. Moreover, it is noteworthy that ophthalmology, as a medical specialty, has fewer examples (e.g., compared to oncology) of personalized medicine and biomarker applications thus far. Understanding the biological action of cannabidiol in preclinical studies is therefore a rational first step to proactively map the pertinent biomarker strategies in clinical proof of concept studies in diabetic retinopathy, and to allow advances at the hitherto neglected intersection of personalized medicine and

  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. Serum Growth Hormone Levels and the Response of Diabetic Retinopathy to Pituitary Ablation*

    PubMed Central

    Wright, A. D.; Kohner, E. M.; Oakley, N. W.; Hartog, M.; Joplin, G. F.; Fraser, T. Russell

    1969-01-01

    Serum growth hormone levels were measured during insulin tolerance tests in 36 patients after yttrium-90 pituitary implantation for diabetic retinopathy. The response of the new blood vessels was more clearly related to loss of growth hormone function than was the improvement of retinal haemorrhages and microaneurysms. The overall response of the retinopathy was greatest when growth hormone function was lost. Since the loss of growth hormone function was related to the loss of other aspects of anterior pituitary function, a unique role of growth hormone in the response of diabetic retinopathy to pituitary ablation could not be established. PMID:5768460

  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

    2016-03-03

    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.

  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

    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

  15. 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

  16. 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

  17. 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

  18. Apelin in epiretinal membranes of patients with proliferative diabetic retinopathy

    PubMed Central

    Lu, Qiang; Ma, Yan; Xu, Yong-sheng

    2014-01-01

    Purpose Formation of epiretinal membranes (ERMs) in the posterior fundus results in visual impairment. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), a neovascular disease. Apelin has been identified as a novel angiogenesis contributor. The aim of this study was to investigate the correlation between apelin and ERMs after PDR. Methods ERM samples were obtained by vitrectomy from 12 subjects with PDR (aged 57±6 years; duration of diabetes 16±7 years), and 12 subjects with idiopathic ERM (aged 68±5 years). The samples were processed for immunohistochemistry and reverse transcription–PCR (RT–PCR). We also analyzed samples from patients with PDR who received an intravitreal injection of bevacizumab (IVB) before vitrectomy. Results The mRNA expression of apelin was significantly higher in the PDR ERMs than in the idiopathic ERMs. Accordingly, immunohistochemical analysis revealed strong expression of apelin in all eight PDR ERMs without IVB, and was double-labeled with glial fibrillary acidic protein antibody (GFAP), platelet endothelial cell adhesion molecule-1 (CD31), cytokeratin (CK) and vascular endothelial growth factor (VEGF) but not with fibronectin. They were mainly located in the adventitia. In contrast, the expression of apelin was lower in the PDR ERMs after IVB and the idiopathic ERMs. Conclusions The results showed that apelin was involved in the formation of ERMs and promoted the formation of adventitia, including glial, endothelial, and RPE cells. Bevacizumab blocked the expression of apelin and regressed gliosis and angiogenesis. PMID:25324682

  19. 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

  20. Screening for Diabetic Retinopathy Using Computer Vision and Physiological Markers

    PubMed Central

    Hann, Christopher E.; Revie, James A.; Hewett, Darren; Chase, J. Geoffrey; Shaw, Geoffrey M.

    2009-01-01

    Background Hyperglycemia and diabetes result in vascular complications, most notably diabetic retinopathy (DR). The prevalence of DR is growing and is a leading cause of blindness and/or visual impairment in developed countries. Current methods of detecting, screening, and monitoring DR are based on subjective human evaluation, which is also slow and time-consuming. As a result, initiation and progress monitoring of DR is clinically hard. Methods Computer vision methods are developed to isolate and detect two of the most common DR dysfunctions—dot hemorrhages (DH) and exudates. The algorithms use specific color channels and segmentation methods to separate these DR manifestations from physiological features in digital fundus images. The algorithms are tested on the first 100 images from a published database. The diagnostic outcome and the resulting positive and negative prediction values (PPV and NPV) are reported. The first 50 images are marked with specialist determined ground truth for each individual exudate and/or DH, which are also compared to algorithm identification. Results Exudate identification had 96.7% sensitivity and 94.9% specificity for diagnosis (PPV = 97%, NPV = 95%). Dot hemorrhage identification had 98.7% sensitivity and 100% specificity (PPV = 100%, NPV = 96%). Greater than 95% of ground truth identified exudates, and DHs were found by the algorithm in the marked first 50 images, with less than 0.5% false positives. Conclusions A direct computer vision approach enabled high-quality identification of exudates and DHs in an independent data set of fundus images. The methods are readily generalizable to other clinical manifestations of DR. The results justify a blinded clinical trial of the system to prove its capability to detect, diagnose, and, over the long term, monitor the state of DR in individuals with diabetes. PMID:20144333

  1. 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

  2. Matrix metalloproteinase-2 in the development of diabetic retinopathy and mitochondrial dysfunction.

    PubMed

    Mohammad, Ghulam; Kowluru, Renu A

    2010-09-01

    In the pathogenesis of diabetic retinopathy, retinal mitochondria become dysfunctional resulting in accelerated apoptosis of its capillary cells. Matrix metalloproteinase-2 (MMP2) is considered critical in cell integrity and cell survival, and diabetes activates MMP2 in the retina and its capillary cells. This study aims at elucidating the mechanism by which MMP2 contributes to the development of diabetic retinopathy. Using isolated bovine retinal endothelial cells, the effect of regulation of MMP2 (by its siRNA and pharmacological inhibitor) on superoxide accumulation and mitochondrial dysfunction was evaluated. The effect of inhibiting diabetes-induced retinal superoxide accumulation on MMP2 and its regulators was investigated in diabetic mice overexpressing mitochondrial superoxide dismutase (MnSOD). Inhibition of MMP2 ameliorated glucose-induced increase in mitochondrial superoxide and membrane permeability, prevented cytochrome c leakage from the mitochondria, and inhibited capillary cell apoptosis. Overexpression of MnSOD protected the retina from diabetes-induced increase in MMP2 and its membrane activator (MT1-MMP), and decrease in its tissue inhibitor (TIMP-2). These results implicate that, in diabetes, MMP2 activates apoptosis of retinal capillary cells by mitochondrial dysfunction increasing their membrane permeability. Understanding the role of MMP2 in the pathogenesis of diabetic retinopathy should help lay ground for MMP2-targeted therapy to retard the development of retinopathy in diabetic patients.

  3. Detecting and treating retinopathy in patients with type I diabetes mellitus. A health policy model.

    PubMed

    Javitt, J C; Canner, J K; Frank, R G; Steinwachs, D M; Sommer, A

    1990-04-01

    Diabetic retinopathy is the major cause of new cases of blindness among working-age Americans. The authors analyzed the medical and economic implications of alternative screening strategies for detecting retinopathy in a diabetic population. The approaches compared included dilated fundus examination at 6-, 12-, and 24-month intervals with and without fundus photography. Potential savings from screening and treatment are based on amounts paid by the federal government for blindness-related disability. Screening for and treating retinopathy in patients with type I diabetes mellitus was cost-effective using all screening strategies. Between 71,474 and 85,315 person years of sight and 76,886 and 94,705 person years of reading vision can be saved for each annual cohort of patients with type I diabetes mellitus when proper laser photocoagulation is administered. This results in a cost savings of $62.1 to $108.6 million. Annual examination of all diabetic patients and semi-annual examination of those with retinopathy was more effective than annual examination with fundus photography. This screening strategy is consistent with the Preferred Practice Pattern for Diabetic Retinopathy of the American Academy of Ophthalmology. PMID:2109299

  4. 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

  5. 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

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

    PubMed Central

    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. 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 ...

  8. 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

  9. 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

  10. 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

  11. 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

  12. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    PubMed Central

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD.

  13. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    PubMed Central

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

  14. 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

  15. 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

  16. Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications.

    PubMed

    Moran, Elizabeth P; Wang, Zhongxiao; Chen, Jing; Sapieha, Przemyslaw; Smith, Lois E H; Ma, Jian-Xing

    2016-09-01

    Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications. PMID:27473938

  17. Comparison of Manual Refraction Versus Autorefraction in 60 Diabetic Retinopathy Patients

    PubMed Central

    Shirzadi, Keyvan; Shahraki, Kourosh; Yahaghi, Emad; Makateb, Ali; Khosravifard, Keivan

    2016-01-01

    Aim: The purpose of the study was to evaluate the comparison of manual refraction versus autorefraction in diabetic retinopathy patients. Material and Methods: The study was conducted at the Be’sat Army Hospital from 2013-2015. In the present study differences between two common refractometry methods (manual refractometry and Auto refractometry) in diagnosis and follow up of retinopathy in patients affected with diabetes is investigated. Results: Our results showed that there is a significant difference in visual acuity score of patients between manual and auto refractometry. Despite this fact, spherical equivalent scores of two methods of refractometry did not show a significant statistical difference in the patients. Conclusion: Although use of manual refraction is comparable with autorefraction in evaluating spherical equivalent scores in diabetic patients affected with retinopathy, but in the case of visual acuity results from these two methods are not comparable. PMID:27703289

  18. Identification of Diabetic Retinopathy Genes through a Genome-Wide Association Study among Mexican-Americans from Starr County, Texas

    PubMed Central

    Fu, Yi-Ping; Hallman, D. Michael; Gonzalez, Victor H.; Klein, Barbara E. K.; Klein, Ronald; Hayes, M. Geoffrey; Cox, Nancy J.; Bell, Graeme I.; Hanis, Craig L.

    2010-01-01

    To identify genetic loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas, completed physical examinations including fundus photography for diabetic retinopathy grading. Individuals with moderate-to-severe non-proliferative and proliferative diabetic retinopathy were defined as cases. Direct genotyping was performed using the Affymetrix GeneChip Human Mapping 100 K Set, and SNPs passing quality control criteria were used to impute markers available in HapMap Phase III Mexican population (MXL) in Los Angeles, California. Two directly genotyped markers were associated with severe diabetic retinopathy at a P-value less than .0001: SNP rs2300782 (P = 6.04 × 10−5) mapped to an intron region of CAMK4 (calcium/calmodulin-dependent protein kinase IV) on chromosome 5, and SNP rs10519765 (P = 6.21 × 10−5) on chromosomal 15q13 in the FMN1 (formin 1) gene. Using well-imputed markers based on the HapMap III Mexican population, we identified an additional 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy at P-value less than .0001. None of these markers were located in traditional candidate genes for diabetic retinopathy or diabetes itself. However, these signals implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic retinopathy. PMID:20871662

  19. Identification of Diabetic Retinopathy Genes through a Genome-Wide Association Study among Mexican-Americans from Starr County, Texas.

    PubMed

    Fu, Yi-Ping; Hallman, D Michael; Gonzalez, Victor H; Klein, Barbara E K; Klein, Ronald; Hayes, M Geoffrey; Cox, Nancy J; Bell, Graeme I; Hanis, Craig L

    2010-01-01

    To identify genetic loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas, completed physical examinations including fundus photography for diabetic retinopathy grading. Individuals with moderate-to-severe non-proliferative and proliferative diabetic retinopathy were defined as cases. Direct genotyping was performed using the Affymetrix GeneChip Human Mapping 100 K Set, and SNPs passing quality control criteria were used to impute markers available in HapMap Phase III Mexican population (MXL) in Los Angeles, California. Two directly genotyped markers were associated with severe diabetic retinopathy at a P-value less than .0001: SNP rs2300782 (P = 6.04 × 10(-5)) mapped to an intron region of CAMK4 (calcium/calmodulin-dependent protein kinase IV) on chromosome 5, and SNP rs10519765 (P = 6.21 × 10(-5)) on chromosomal 15q13 in the FMN1 (formin 1) gene. Using well-imputed markers based on the HapMap III Mexican population, we identified an additional 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy at P-value less than .0001. None of these markers were located in traditional candidate genes for diabetic retinopathy or diabetes itself. However, these signals implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic retinopathy. PMID:20871662

  20. Bone marrow-CNS connections: Implications in the pathogenesis of diabetic retinopathy

    PubMed Central

    Douglas, Yellowlees; Bhatwadekar, Ashay D.; Shaw, Lynn C.; Carnegie, Debra; Caballero, Sergio; Li, Quihong; Calzi, Sergio Li; Raizada, Mohan K.; Stitt, Alan W.; Grant, Maria B.

    2013-01-01

    Diabetic retinopathy is the fourth most common cause of blindness in adults. Current therapies, including anti-VEGF therapy, have partial efficacy in arresting the progression of proliferative diabetic retinopathy and diabetic macular edema. This review provides an overview of a novel, innovative approach to viewing diabetic retinopathy as the result of an inflammatory cycle that affects the bone marrow (BM) and the central and sympathetic nervous systems. Diabetes associated inflammation may be the result of BM neuropathy which skews haematopoiesis towards generation of increased inflammatory cells but also reduced production of endothelial progenitor cells responsible for maintaining healthy endothelial function and renewal. The resulting systemic inflammation further impacts the hypothalamus, promoting insulin resistance and diabetes, and initiates an inflammatory cascade that adversely impacts both macrovascular and microvascular complications, including diabetic retinopathy (DR). This review examines the idea of using anti-inflammatory agents that cross not only the blood-retinal barrier to enter the retina but also have the capability to target the central nervous system and cross the blood-brain barrier to reduce neuroinflammation. This neuroinflammation in key sympathetic centers serves to not only perpetuate BM pathology but promote insulin resistance which is characteristic of type 2 diabetic patients (T2D) but is also seen in T1D. A case series of morbidly obese T2D patients with retinopathy and neuropathy treated with minocycline, a well-tolerated antibiotic that crosses both the blood-retina and blood-brain barrier is presented. Our results indicates that minocycine shows promise for improving visual acuity, reducing pain from peripheral neuropathy, promoting weight loss and improving blood pressure control and we postulate that these observed beneficial effects are due to a reduction of chronic inflammation. PMID:22609081

  1. Bone marrow-CNS connections: implications in the pathogenesis of diabetic retinopathy.

    PubMed

    Yellowlees Douglas, Jane; Bhatwadekar, Ashay D; Li Calzi, Sergio; Shaw, Lynn C; Carnegie, Debra; Caballero, Sergio; Li, Quihong; Stitt, Alan W; Raizada, Mohan K; Grant, Maria B

    2012-09-01

    Diabetic retinopathy is the fourth most common cause of blindness in adults. Current therapies, including anti-VEGF therapy, have partial efficacy in arresting the progression of proliferative diabetic retinopathy and diabetic macular edema. This review provides an overview of a novel, innovative approach to viewing diabetic retinopathy as the result of an inflammatory cycle that affects the bone marrow (BM) and the central and sympathetic nervous systems. Diabetes associated inflammation may be the result of BM neuropathy which skews haematopoiesis towards generation of increased inflammatory cells but also reduces production of endothelial progenitor cells responsible for maintaining healthy endothelial function and renewal. The resulting systemic inflammation further impacts the hypothalamus, promoting insulin resistance and diabetes, and initiates an inflammatory cascade that adversely impacts both macrovascular and microvascular complications, including diabetic retinopathy (DR). This review examines the idea of using anti-inflammatory agents that cross not only the blood-retinal barrier to enter the retina but also have the capability to target the central nervous system and cross the blood-brain barrier to reduce neuroinflammation. This neuroinflammation in key sympathetic centers serves to not only perpetuate BM pathology but promote insulin resistance which is characteristic of type 2 diabetic patients (T2D) but is also seen in T1D. A case series of morbidly obese T2D patients with retinopathy and neuropathy treated with minocycline, a well-tolerated antibiotic that crosses both the blood-retina and blood-brain barrier is presented. Our results indicates that minocycine shows promise for improving visual acuity, reducing pain from peripheral neuropathy, promoting weight loss and improving blood pressure control and we postulate that these observed beneficial effects are due to a reduction of chronic inflammation. PMID:22609081

  2. 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.

  3. 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.

  4. Wide-Field Megahertz OCT Imaging of Patients with Diabetic Retinopathy

    PubMed Central

    Reznicek, Lukas; Kolb, Jan P.; Klein, Thomas; Mohler, Kathrin J.; Wieser, Wolfgang; Huber, Robert; Kernt, Marcus; Märtz, Josef; Neubauer, Aljoscha S.

    2015-01-01

    Purpose. To evaluate the feasibility of wide-field Megahertz (MHz) OCT imaging in patients with diabetic retinopathy. Methods. A consecutive series of 15 eyes of 15 patients with diagnosed diabetic retinopathy were included. All patients underwent Megahertz OCT imaging, a close clinical examination, slit lamp biomicroscopy, and funduscopic evaluation. To acquire densely sampled, wide-field volumetric datasets, an ophthalmic 1050 nm OCT prototype system based on a Fourier-domain mode-locked (FDML) laser source with 1.68 MHz A-scan rate was employed. Results. We were able to obtain OCT volume scans from all included 15 patients. Acquisition time was 1.8 seconds. Obtained volume datasets consisted of 2088 × 1044 A-scans of 60° of view. Thus, reconstructed en face images had a resolution of 34.8 pixels per degree in x-axis and 17.4 pixels per degree. Due to the densely sampled OCT volume dataset, postprocessed customized cross-sectional B-frames through pathologic changes such as an individual microaneurysm or a retinal neovascularization could be imaged. Conclusions. Wide-field Megahertz OCT is feasible to successfully image patients with diabetic retinopathy at high scanning rates and a wide angle of view, providing information in all three axes. The Megahertz OCT is a useful tool to screen diabetic patients for diabetic retinopathy. PMID:26273665

  5. Diabetic retinopathy in native and non-native Sarawakians--findings from the Diabetic Eye Registry.

    PubMed

    Mallika, P S; Aziz, S; Goh, P P; Lee, P Y; Cheah, W L; Chong, M S; Tan, A K

    2012-08-01

    This study aims to determine the risk factors associated with diabetic retinopathy (DR) among natives and non-natives Sarawakians who were seen at 3 public hospitals and one health clinic in Sarawak. It is a cross sectional study where data on patients with DM were collected by staff at these healthcare facilities and entered into the web-based Diabetic Eye Registry. Univariate and multivariate analysis was used to determine the association factors for DR. DR was significantly less associated with natives (24.4%) compared to non-native Sarawakians (34.1%) (p < 0.001). The odds of getting DR was higher in patients whose duration of DM was more than 20 years (OR = 2.6), who have renal impairment (OR = 1.7) and non-natives (OR = 1.4).

  6. Diabetic retinopathy and blockade of the renin-angiotensin system: new data from the DIRECT study programme.

    PubMed

    Wright, A D; Dodson, P M

    2010-01-01

    The pathogenesis and medical management of diabetic retinopathy is reviewed. The importance of good control of blood glucose and blood pressure remain key elements in the prevention and treatment of diabetic retinopathy, and a number of specific metabolic pathways have been identified that may be useful additional targets for therapeutic intervention. Trial data, however, aimed specifically to answer the questions of optimum medical management are limited, so the DIRECT study of renin-angiotensin blockade using oral candesartan 32 mg daily is a welcome addition to our knowledge. This arose from the promising improvement of retinopathy outcomes in the EUCLID study of lisinopril in type I diabetes. In DIRECT, 5 years of candesartan treatment in type I diabetes reduced the incidence of retinopathy by two or more steps (EDTRS) in severity by 18% (P=0.0508) and, in a post hoc analysis, reduced the incidence of retinopathy by three-step progression by 35% (P=0.034). In type I diabetes patients there was no effect on progression of established retinopathy. In contrast, in type II diabetes, 5 years of candesartan treatment resulted in 34% regression of retinopathy (P=0.009). Importantly, an overall significant change towards less-severe retinopathy was noted in both type I and II diabetes (Pdiabetic retinopathy, to prevent the problem in type I diabetes and to treat the early stages in type II diabetes.

  7. 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

  8. 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.

  9. NaoXinTong Inhibits the Development of Diabetic Retinopathy in db/db Mice

    PubMed Central

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

    2015-01-01

    Buchang NaoXinTong capsule (NXT) is a Chinese Materia Medica standardized product extracted from 16 Chinese traditional medical herbs and widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. Formation of microaneurysms plays an important role in the development of diabetic retinopathy. In this study, we investigated if  NXT can protect diabetic mice against the development of diabetic retinopathy. The db/db mice (~6 weeks old), a diabetic animal model, were divided into two groups and fed normal chow or plus NXT for 14 weeks. During the treatment, fasting blood glucose levels were monthly determined. After treatment, retinas were collected to determine retinal thickness, accumulation of carbohydrate macromolecules, and caspase-3 (CAS-3) expression. Our results demonstrate that administration of NXT decreased fasting blood glucose levels. Associated with the decreased glucose levels, NXT blocked the diabetes-induced shrink of multiple layers, such as photoreceptor layer and outer nuclear/plexiform layers, in the retina. NXT also inhibited the diabetes-induced expression of CAS-3 protein and mRNA, MMP-2/9 and TNFα mRNA, accumulation of carbohydrate macromolecules, and formation of acellular capillaries in the retina. Taken together, our study shows that NXT can inhibit the development of diabetic retinopathy and suggests a new potential application of NXT in clinic. PMID:25821481

  10. Plasma malondialdehyde (MDA) and anti-oxidant status in diabetic retinopathy.

    PubMed

    Kumawat, Manjulata; Kharb, Simmi; Singh, Veena; Singh, Neelima; Singh, S K; Nada, Manisha

    2014-01-01

    Hyperglycaemia and dyslipidaemia in diabetes mellitus induce increased lipid peroxidation and peroxyl radical formation is an important mechanism in genesis of micro-angiopathy. We took up a study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde (MDA) and antioxidant enzyme status in type 2 diabetes mellitus patients with and without retinopathy and compared them with a control non-diabetic group. MDA was significantly elevated (p < 0.001) in both the diabetic groups whereas antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and reduced glutathione (GSH), etc, were significantly decreased (p < 0.001) which might be helpful in risk assessment of various complications of diabetes mellitus. The study included 100 subjects of age group 50-70 years, out of which 50 patients were non-insulin dependent diabetes mellitus (NIDDM) with retinopathy and rest 50 age and sex matched apparently healthy individuals (control group). The status of fasting blood sugar (FBS), postprandial blood sugar (PPBS), total cholesterol (TC), triglyceride (Tg), HDL-cholesterol, LDL-cholesterol, VLDL- cholesterol, GPx, GR, CAT, SOD, MDA were determined. The results showed significant increase (p < 0.001) in FBS, PPBS, TC, TG, LDL-C, VLDL-C, CAT, MDA while HDL-C, GSH, GPx, GR and SOD were found to be decreased significantly (p < 0.001). The data suggest that alteration in anti-oxidant status and MDA may help to predict the risk of diabetic retinopathy.

  11. The role of diabetic retinopathy in blindness and poor sight in Split-Dalmatia County 2000-2010.

    PubMed

    Galetović, Davor; Olujić, Ivana; Znaor, Ljubo; Bućan, Kajo; Karlica, Dobrila; Lesin, Mladen; Susac, Tihomir

    2013-12-01

    Diabetic retinopathy is the fifth leading cause of blindness in the world. The aim of this study was to determine the number of blind persons in the Split-Dalmatia County in the 2000-2010 period and how many of them are blind due to diabetic retinopathy. Records of 160 members of the Association of the Blind in the Split-Dalmatia County, enrolled from 2000 to 2010, were retrospectively analyzed. The leading causes of blindness were diabetic retinopathy (25.6%), glaucoma (13.1%), retinal dystrophy (16.2%), and age related macular degeneration (11.8%). The annual incidence of blindness was 8.4/100,000 inhabitants. The largest number of the blind were found in the 70-80 (21.2%) to > 80 (24.3%) age group. Diabetic retinopathy was the cause of blindness in 24 (15%) men and 17 (10.6%) women. The annual incidence of diabetic retinopathy was 2.16 per 100,000. No case of blindness due to diabetic retinopathy was diagnosed in patients younger than 30 years of age, while the highest prevalence was found in the 70-80 age group (34%). Proliferative diabetic retinopathy was the cause of blindness in 92.7% and nonproliferative diabetic retinopathy in 7.3% of cases. Study results show that diabetic retinopathy remains the leading cause of blindness. Early identification of high-risk patients is the key factor in prevention and timely detection of ophthalmoscopic changes, thus enabling effective and duly treatment.

  12. Investigating Factors Associated with Depression of Type 2 Diabetic Retinopathy Patients in China

    PubMed Central

    Qian, Duo; Dong, Qing; Gu, Zhifeng

    2015-01-01

    Aims and objectives To assess the depression status of type 2 diabetic retinopathy patients in Nantong China and to identify factors associated with depression. Methods Two hundred and ninety-four patients with type 2 diabetic retinopathy were recruited from the Affiliated Hospital of Nantong University. The severity of DR was measured in the worse eye. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D); the quality of life was measured with the Medical Outcomes Study Short Form 36 (SF-36). The logistic regression analyses were used to identify the independent factors of depression. Results The mean age of the study subjects was 57.77 years (SD: 9.64). Approximately 35.7% of subjects reported depressive symptoms (n = 105).Multiple logistic regression analyses showed that female gender (p = 0.014), low monthly income (p = 0.01), poor vision in the better eye (P = 0.002), laser treatment history (p = 0.01) were significant risk factors for depression. The quality of life of individuals with CES-D score<16 was significantly better compared with individuals with CES-D score≥16. Conclusion The reported depressive symptoms among type 2 diabetic retinopathy population is higher in Nantong China. Gender, salary, vision acuity and treatment history were important risk factors linked to this disorder in the Chinese type 2 diabetic retinopathy population from Nantong. More attention by medical care personnel needs to be paid to the psychological health of this population. PMID:26151365

  13. 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…

  14. 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…

  15. 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 ...

  16. 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

  17. Automated classifiers for early detection and diagnosis of retinopathy in diabetic eyes

    PubMed Central

    2014-01-01

    Background Artificial neural networks (ANNs) have been used to classify eye diseases, such as diabetic retinopathy (DR) and glaucoma. DR is the leading cause of blindness in working-age adults in the developed world. The implementation of DR diagnostic routines could be feasibly improved by the integration of structural and optical property test measurements of the retinal structure that provide important and complementary information for reaching a diagnosis. In this study, we evaluate the capability of several structural and optical features (thickness, total reflectance and fractal dimension) of various intraretinal layers extracted from optical coherence tomography images to train a Bayesian ANN to discriminate between healthy and diabetic eyes with and with no mild retinopathy. Results When exploring the probability as to whether the subject’s eye was healthy (diagnostic condition, Test 1), we found that the structural and optical property features of the outer plexiform layer (OPL) and the complex formed by the ganglion cell and inner plexiform layers (GCL + IPL) provided the highest probability (positive predictive value (PPV) of 91% and 89%, respectively) for the proportion of patients with positive test results (healthy condition) who were correctly diagnosed (Test 1). The true negative, TP and PPV values remained stable despite the different sizes of training data sets (Test 2). The sensitivity, specificity and PPV were greater or close to 0.70 for the retinal nerve fiber layer’s features, photoreceptor outer segments and retinal pigment epithelium when 23 diabetic eyes with mild retinopathy were mixed with 38 diabetic eyes with no retinopathy (Test 3). Conclusions A Bayesian ANN trained on structural and optical features from optical coherence tomography data can successfully discriminate between healthy and diabetic eyes with and with no retinopathy. The fractal dimension of the OPL and the GCL + IPL complex predicted by the Bayesian radial

  18. Necrotising herpetic retinopathy in patients with advance HIV disease.

    PubMed Central

    Miller, R F; Brink, N S; Cartledge, J; Sharvell, Y; Frith, P

    1997-01-01

    OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor. Images PMID:9582461

  19. Usefulness of the Vitreous Fluid Analysis in the Translational Research of Diabetic Retinopathy

    PubMed Central

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

    2012-01-01

    Diabetic retinopathy (DR) is the major cause of acquired blindness in working-age adults. Current treatments for DR (laser photocoagulation, intravitreal corticosteroids, intravitreal antivascular endothelial growth factor (VEGF) agents, and vitreo-retinal surgery) are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of the disease are needed. Vitreous fluid obtained from diabetic patients undergoing vitreoretinal surgery is currently used to explore the events that are taking place in the retina for clinical research. However, several confounding factors such as vitreous haemorrhage and concentration of vitreous proteins should be considered in the analysis of the results. In this paper we will focus on the vitreous fluid as a tool for exploring the mediators of DR and in particular the molecules related to inflammatory pathways. In addition, their role in the pathogenesis of DR will be discussed. The usefulness of new technologies such as flow cytometry and proteomics in identifying new candidates involved in the inflammatory process that occurs in DR will be overviewed. Finally, a more personalized treatment based on vitreous fluid analysis aiming to reduce the burden associated with DR is suggested. PMID:23028204

  20. Cellular Mechanisms of High Mobility Group 1 (HMGB-1) Protein Action in the Diabetic Retinopathy

    PubMed Central

    Santos, Andrea Rachelle C.; Dvoriantchikova, Galina; Li, Yiwen; Mohammad, Ghulam; Abu El-Asrar, Ahmed M.; Wen, Rong; Ivanov, Dmitry

    2014-01-01

    Diabetic retinopathy is one of the main microvascular complications of diabetes and remains one of the leading causes of blindness worldwide. Recent studies have revealed an important role of inflammatory and proangiogenic high mobility group 1 (HMGB-1) cytokine in diabetic retinopathy. To elucidate cellular mechanisms of HMGB-1 activity in the retina, we performed this study. The histological features of diabetic retinopathy include loss of blood-vessel pericytes and endothelial cells, as well as abnormal new blood vessel growth. To establish the role of HMGB-1 in vulnerability of endothelial cells and pericytes, cultures of these cells, or co-cultures with glial cells, were treated with HMGB-1 and assessed for survival after 24 hours. The expression levels of the cytokines, chemokines, and cell adhesion molecules in glial and endothelial cells were tested by quantitative RT-PCR to evaluate changes in these cells after HMGB-1 treatment. Animal models of neovascularization were also used to study the role of HMGB-1 in the retina. We report that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate death of endothelial cells. We also found that HMGB-1 affects endothelial cell activity. However, we did not observe a difference in the levels of neovascularization between HMGB-1-treated eyes compared to the control eyes, nor in the levels of proangiogenic cytokine VEGF-A expression between glial cells treated with HMGB-1 and control cells. Our data also indicate that HMGB-1 is not involved in retinal neovascularization in the oxygen-induced retinopathy model. Thus, our data suggest that retinal pericyte and endothelial injury and death in diabetic retinopathy may be due to HMGB-1-induced cytotoxic activity of glial cells as well as the direct effect of HMGB-1 on endothelial cells. At the same time, our findings indicate that HMGB-1 plays an insignificant role in retinal and choroidal neovascularization. PMID

  1. 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

  2. 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

  3. Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy

    PubMed Central

    Chantelau, E

    1998-01-01

    BACKGROUND—Acute reduction of chronic hyperglycaemia can accelerate early diabetic retinopathy. In adolescent patients with Mauriac's syndrome, this phenomenon is related to an upregulation of subnormal serum IGF-1 levels.
AIM—To obtain longitudinal data on serum IGF-1 and retinopathy status in poorly controlled adult insulin dependent (type 1) diabetic patients without Mauriac's syndrome, in whom hyperglycaemia is reduced by intensive insulin therapy.
METHODS—Four patients with chronic severe insulin deficiency and early microangiopathy were studied prospectively. Changes in plasma glucose, HbA1c, serum IGF-1 levels, proteinuria, retinopathy, and clinical status were followed up closely.
RESULTS—Reducing hyperglycaemia from >16 mmol/l (equivalent to HbA1c >11%) to <10 mmol/l (HbA1c <8%) within 5 months increased serum IGF-1 levels by 70-220%. While proteinuria and symptomatic neuropathy regressed, retinopathy progressed from the mild to the severe non-proliferative stage with maculopathy (n=4), and to the proliferative stage (n=1). Laser coagulation was commenced upon the appearance of sight threatening macular oedema (n=4).
CONCLUSION—Upregulation of serum IGF-1 preceding retinal deterioration in these patients suggests a cause-effect relation, consistent with earlier experimental and clinical data. 

 Keywords: diabetes mellitus; macular oedema; metabolic control; intensive therapy; glycated haemoglobin A1c; growth factors PMID:9924360

  4. 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

  5. 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

  6. Icariin Ameliorates Streptozotocin-Induced Diabetic Retinopathy in Vitro and in Vivo

    PubMed Central

    Xin, Hua; Zhou, Feng; Liu, Tao; Li, Guang-Yong; Liu, Jing; Gao, Zhe-Zhu; Bai, Guang-Yi; Lu, Hong; Xin, Zhong-Cheng

    2012-01-01

    This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two groups; one group received ICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a placebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV), vascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a expression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at various concentrations (0, 101, 102, 103 nmol/mL) on neurite growth were investigated also in retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous pathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as decreased Collagen IV and Müller cell content) were noted in the retinal vessels of diabetic rats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced neurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations are indicated. PMID:22312291

  7. 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.

  8. 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

  9. 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.

  10. Candidate gene association study for diabetic retinopathy in Chinese patients with type 2 diabetes

    PubMed Central

    Yang, Xiufen; Deng, Yu; Gu, Hong; Ren, Xuetao; Li, Na; Lim, Apiradee; Snellingen, Torkel; Liu, Xipu; Wang, Ningli

    2014-01-01

    Purpose To investigate whether variants in a set of eight candidate genes are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). Methods Case-control study. Patients with T2DM were recruited from the Desheng community in urban Beijing and assigned into a DR group or diabetic without retinopathy (DWR) group, based on the duration of diabetes and grading of fundus images. Twenty-six single-nucleotide polymorphisms (SNPs) within eight candidate genes, including PPARγ, vascular endothelial growth factor (VEGF) and its receptor kinase insert domain receptor (KDR), erythropoietin, aldose reductase, protein kinase C-β, angiotensin-converting enzyme, and intercellular adhesion molecule 1, were analyzed using the MassARRAY genotyping system. Results A total of 500 patients with T2DM (216 with DR and 284 with DWR) were enrolled in the study. Significant associations of DR were noted with genotypes of four SNPs—rs699947 (p<0.001), rs833061 (p=0.001), rs13207351 (p<0.001), and rs2146323 (p=0.006)—in the VEGF gene and one variant, rs2071559, in the KDR gene (p=0.034). After adjustment for covariates, significant association of DR remained with the homozygous genotype of the minor allele for the SNPs rs699947 (odds ratio [OR] = 3.54, 95% confidence interval [CI]: 1.12–11.19), rs833061 (OR = 3.72, 95% CI: 1.17–11.85), rs13207351 (OR = 3.76, 95% CI: 1.21–11.71), and rs2146323 (OR = 2.8, 95% CI: 1.46–5.37) in the VEGF gene as well as the SNP rs2071559 (OR = 1.62, 95% CI: 1.08–2.41) in the KDR gene. However, only rs699947 and rs13207351 in the VEGF gene remained statistically significant after Bonferroni correction. No associations were found in other genes tested. Conclusions These data expanded previous observations on the association of DR with variants in the VEGF gene in Chinese patients with T2DM. Moreover, a possible association between DR and KDR polymorphisms is suggested. PMID:24623964

  11. Surgical management of retinal diseases: proliferative diabetic retinopathy and traction retinal detachment.

    PubMed

    Cruz-Iñigo, Yousef J; Acabá, Luis A; Berrocal, Maria H

    2014-01-01

    Current indications for pars plana vitrectomy in patients with proliferative diabetic retinopathy (PDR) include vitreous hemorrhage, tractional retinal detachment (TRD), combined tractional and rhegmatogenous retinal detachment (CTRRD), diabetic macular edema associated with posterior hyaloidal traction, and anterior segment neovascularization with media opacities. This chapter will review the indications, surgical objectives, adjunctive pharmacotherapy, microincision surgical techniques, and outcomes of diabetic vitrectomy for PDR, TRD, and CTRRD. With the availability of new microincision vitrectomy technology, wide-angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from PDR.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Non-stereo fundus photography as a screening procedure for diabetic retinopathy among patients with type II diabetes. Compared with 60D enhanced slit-lamp examination.

    PubMed

    Kalm, H; Egertsen, R; Blohmé, G

    1989-10-01

    The spectrum of diabetic retinopathy, the need for fundus screening and the evaluation of two presumptive screening methods, was investigated in a population based study among patients with type II diabetes. Retinal evaluation was performed in 86.9% of the known diabetic population. Background diabetic retinopathy was detected in 37.8%, pre-proliferative in 1.1% and proliferative retinopathy in 3.8%. Diabetic maculopathy was found in 24.3% of the patients. Laser therapy was considered in 11.4% of the patients due to diabetic retinopathy, and in 14.6% when venous occlusive diseases were included. Two methods, a slit-lamp observation enhanced by a 60D lens and reading from two non-stereo photographs of the posterior pole, were evaluated among 154 patients willing and mentally capable of being examined by either method. The sensitivity of the photographic method was 87/97% (right eye/left eye) when detecting background retinopathy and 81/80% for maculopathy versus 69/61% and 79/63%, respectively, with the slit-lamp method. The photographic method could be applied in 93% of the patients mentally capable of cooperation. Only 5 or 6 patients could be examined per hour with the 60D slit-lamp compared with 30-35 examined by reading retinal photographs. The photographic method is recommended as an easy and reliable screening device for diabetic retinopathy among patients with type II diabetes.

  17. 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

  18. Adipose-derived stem cells from diabetic mice show impaired vascular stabilization in a murine model of diabetic retinopathy.

    PubMed

    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; Peirce, Shayn M; Yates, Paul A

    2015-05-01

    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.

  19. 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

  20. 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

  1. Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy.

    PubMed

    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.

  2. 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

  3. Optimal area of retinal photocoagulation necessary for suppressing active iris neovascularisation associated with diabetic retinopathy.

    PubMed

    Shiraya, Tomoyasu; Kato, Satoshi; Shigeeda, Takashi

    2014-10-01

    To determine the optimal area of retinal photocoagulation required for suppressing active neovascularisation (NVI) associated with diabetic retinopathy. We studied 1 eye each of 4 patients in whom active NVI was ophthalmoscopically shown to have been suppressed by additional photocoagulation. These patients initially underwent pan-retinal photocoagulation for diabetic retinopathy at another hospital, but NVI developed subsequently. We compared the areas of photocoagulation before and after additional photocoagulation and compared the area of retinal photocoagulation. The photocoagulated areas before and after additional photocoagulation in the four eyes were 20.7 and 45.2, 36.6 and 56.3, 30.4 and 67.4, and 11.7 and 53.4 %, respectively. The area of retinal photocoagulation required to suppress active NVI is calculated to be ~50 %.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Prevalence of diabetic retinopathy in individuals with type 2 diabetes who had recorded diabetic retinopathy from retinal photographs in Catalonia (Spain)

    PubMed Central

    Rodriguez-Poncelas, Antonio; Miravet-Jiménez, Sònia; Casellas, Aina; Barrot-De La Puente, Joan Francesc; Franch-Nadal, Josep; López-Simarro, Flora; Mata-Cases, Manel; Mundet-Tudurí, Xavier

    2015-01-01

    Background/aims Retinal photography with a non-mydriatic camera is the method currently employed for diabetic retinography (DR) screening. We designed this study in order to evaluate the prevalence and severity of DR, and associated risk factors, in patients with type 2 diabetes (T2DM) screened in Catalan Primary Health Care. Methods Retrospective, cross-sectional, population based study performed in Catalonia (Spain) with patients with T2DM, aged between 30 years and 90 years (on 31 December 2012) screened with retinal photography and whose DR category was recorded in their medical records. DR was classified as: no apparent retinopathy (no DR), mild non-proliferative DR (mild NPDR), moderate NPDR, severe NPDR, proliferative DR (PDR) and diabetic macular oedema (DMO). Non-vision threatening DR (non-VTDR) included mild and moderate NPDR; VTDR included severe NPDR, PDR and DMO. Clinical data were obtained retrospectively from the SIDIAP database (System for Research and Development in Primary Care). Results 108 723 patients with T2DM had been screened with retinal photography. The prevalence of any kind of DR was 12.3% (95% CI 12.1% to 12.5%). Non-VTDR and VTDR were present in 10.8% (mild 7.5% and moderate NPDR 3.3%) and 1.4% (severe NPDR 0.86%, PDR 0.36% and DMO 0.18%) of the study patients, respectively. Conclusions The prevalence of any type of DR in patients with T2DM screened with retinal photography was lower when compared with earlier studies. PMID:26089211

  9. Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

    PubMed

    Park, Susanna S

    2016-04-01

    Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

  10. 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

  11. 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

  12. [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.

  13. 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

  14. 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

  15. 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

  16. Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population

    PubMed Central

    Romero-Aroca, Pedro; de la Riva-Fernandez, Sofia; Valls-Mateu, Aida; Sagarra-Alamo, Ramon; Moreno-Ribas, Antonio; Soler, Nuria

    2016-01-01

    Background/aims To determine the changes in the incidence of diabetic retinopathy (DR), diabetic macular oedema (DMO) and their risk factors in a population-based study of patients with diabetes mellitus (DM) referred to our 16 Primary Health Care Areas (HCAs). Methods Prospective population-based study of a total of 15 396 Caucasian patients with DM, who represent 86.53% of the total patients with DM in our HCAs, were studied over an 8-year follow-up period. All patients were screened with a mean follow-up of 3.18±1.11 times for each patient over the 8 years. Results The yearly mean value of any DR was 8.37±2.19% (8.09%–8.99%); of advanced DR yearly mean value of 0.46±0.22% (0.03–0.78); and of DMO a yearly mean value of 2.19±0.18% (2%–2.49%). A clear increase was observed in the last 3 years, any DR increased from 8.09% in 2007 to 8.99% in 2014, and DMO from 2% in 2007 to 2.49% in 2014. These increases were more evident in some age groups. For patients with any DR aged 41–50 and 51–60 and for patients with advanced DR aged 41–50, 51–60 and 61–70, the increase was more marked, related to an increase in HbA1c values or to patients treated with insulin. Conclusions An increase in the incidence of DR and DMO was observed, especially in the younger patients aged between 31 and 70 years. This is linked to bad metabolic control of DM. Our results suggest a greater number of ocular complications in the near future, such as neovascular glaucoma, if these current findings are not addressed. PMID:26769672

  17. 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

  18. 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

  19. 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.

  20. 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

  1. Costs of mobile screening for diabetic retinopathy: a practical framework for rural populations.

    PubMed

    Lee, S J; McCarty, C A; Taylor, H R; Keeffe, J E

    2001-08-01

    Australia's rural and remote residents experience considerably higher hospitalisation and death rates due to diabetes than their metropolitan counterparts. There is clearly a need for improved diabetes care services in these areas and interventions that target conditions associated with diabetes will yield beneficial results for the community. All people with diabetes are at risk for diabetic retinopathy, which can cause vision loss and blindness. Although vision loss and blindness due to diabetes is nearly 100% preventable through regular eye examinations, 35% of Victoria's rural population with diabetes do not have their eyes examined on a regular basis. A pilot, mobile screening program for the early detection of diabetic eye disease was conducted in rural Victoria and proved to be a successful model of adjunct eye care for people with diabetes. Actual costs from the pilot screening were applied to a permanent model for rural eye care. At A$41 per participant, costs for mobile screening were competitive with Medicare rebate costs for eye examinations. The model addresses barriers of accessibility and availability, targets a portion of the rural population with diabetes that is not otherwise having eye examinations, and is cost-saving to the Government. PMID:11488703

  2. 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. PMID:26681813

  3. Histamine, ZO-1 and increased blood-retinal barrier permeability in diabetic retinopathy.

    PubMed Central

    Gardner, T W

    1995-01-01

    PURPOSES: First, to develop an improved retinal capillary endothelial cell culture system which exhibits some of the physiologic features of the bloodretinal barrier; second, to use this model to determine how histamine and chemical conditions of diabetes effect expression of the tight junction protein, ZO-1; and third, to discuss application of the Henle-Koch postulates to the problem of diabetic retinopathy. METHODS: Bovine retinal capillary endothelial cells were exposed to varying serum and growth factor concentrations, as well as astrocyte-conditioned medium, in order to establish a model of the blood-retinal barrier. Cells were also exposed to varying concentrations of histamine, and of insulin and glucose. The expression of ZO-1 tight junction protein was determined by immunocytochemistry and immunoblotting. RESULTS: Modified concentrations of growth factors reduced endothelial cell proliferation, without reducing viability. Astrocyte conditioned medium increased ZO-1 protein content. Histamine reduced ZO-1 protein content. Both high glucose (20mM) and low insulin (10(-12)M) reduced ZO-1 protein content compared to control conditions (5mM glucose and 10(-9) M insulin). CONCLUSIONS: Control of culture conditions results in a more physiologic in vitro model of the blood-retinal barrier. Soluble factors from astrocytes promote tight junction formation. Both histamine and chemical conditions of diabetes diminish tight junction formation. These factors may mediate blood-retinal barrier breakdown in diabetic retinopathy. Henle-Koch postulates for diabetic retinopathy are presented. Images FIGURE 1A FIGURE 1B FIGURE 2 A FIGURE 2 B FIGURE 3 A FIGURE 3 B FIGURE 3 C FIGURE 4 FIGURE 5 A FIGURE 5 B FIGURE 6 FIGURE 7 FIGURE 8 PMID:8719694

  4. 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

  5. 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

  6. Automatic detection of blood vessels in retinal images for diabetic retinopathy diagnosis.

    PubMed

    Raja, D Siva Sundhara; Vasuki, S

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients. DR is mainly caused due to the damage of retinal blood vessels in the diabetic patients. It is essential to detect and segment the retinal blood vessels for DR detection and diagnosis, which prevents earlier vision loss in diabetic patients. The computer aided automatic detection and segmentation of blood vessels through the elimination of optic disc (OD) region in retina are proposed in this paper. The OD region is segmented using anisotropic diffusion filter and subsequentially the retinal blood vessels are detected using mathematical binary morphological operations. The proposed methodology is tested on two different publicly available datasets and achieved 93.99% sensitivity, 98.37% specificity, 98.08% accuracy in DRIVE dataset and 93.6% sensitivity, 98.96% specificity, and 95.94% accuracy in STARE dataset, respectively.

  7. Automatic Detection of Blood Vessels in Retinal Images for Diabetic Retinopathy Diagnosis

    PubMed Central

    Siva Sundhara Raja, D.; Vasuki, S.

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients. DR is mainly caused due to the damage of retinal blood vessels in the diabetic patients. It is essential to detect and segment the retinal blood vessels for DR detection and diagnosis, which prevents earlier vision loss in diabetic patients. The computer aided automatic detection and segmentation of blood vessels through the elimination of optic disc (OD) region in retina are proposed in this paper. The OD region is segmented using anisotropic diffusion filter and subsequentially the retinal blood vessels are detected using mathematical binary morphological operations. The proposed methodology is tested on two different publicly available datasets and achieved 93.99% sensitivity, 98.37% specificity, 98.08% accuracy in DRIVE dataset and 93.6% sensitivity, 98.96% specificity, and 95.94% accuracy in STARE dataset, respectively. PMID:25810749

  8. Efficacy of troxerutin on streptozotocin-induced rat model in the early stage of diabetic retinopathy.

    PubMed

    Chung, Han Kook; Choi, Seul Min; Ahn, Byoung Ok; Kwak, Hyun Hee; Kim, Jeong Hoon; Kim, Won Bae

    2005-01-01

    The vascular changes associated with early diabetic retinopathy, which include the formation of microaneurysms and acellular capillaries, vessel dilation, vascular endothelial growth factor expression, were investigated experimentally in streptozotocin-induced diabetic rats treated with antioxidants: troxerutin (trihydroxy-ethylrutoside, CAS 7085-55-4), Vaccinium myrtillus, and calcium dobesilate (hydroquinone calcium sulfonate, CAS 20123-80-2). The development and progression of retinopathy was followed using fundus photography. After 3 months, the rats were sacrificed and half of the eyes were prepared for neovascularization analysis, and the other half were used for VEGF (vascular endothelial growth factor) analysis. The results from fundus photography and ADPase (adenosine diphosphatase) staining were quantified by the percentage area of the retinal vasculature using a commercial image analyzer. The VEGF protein in the retinal homogenates was assessed using an ELISA (enzyme linked immunosorbent assay) kit and VEGF-mRNA by RT-PCR (reverse transcription polymerase chain reaction). In the ADPase stain, the retinal vascular percent area increased significantly in the diabetic control. Neovascularization and aneurysms were observed in the diabetic control and were attenuated by 50 mg/kg troxerutin, but the retinal vascular percentage area was not significantly different from the diabetic control. The VEGF protein concentration was higher in diabetic rats than in the nondiabetic rats (21.5 +/- 2.1 vs 27.7 +/- 5.8 pg/mg, p < 0.05), and this increase was attenuated by 10 mg/kg troxerutin (24.5 +/- 3.8 pg/mg, p < 0.05) and prevented by 50 mg/kg troxerutin (19.5 +/- 2.2 pg/mg, p < 0.05). However, there were no significant differences between the groups. The VEGF-mRNA density showed a increasing tendency by 20% in the diabetic rats compared with the non-diabetic rats (1.0 +/- 0.1 vs 1.2 +/- 0.1 VEGF/beta-actin), and this increase was corrected by 10 mg/kg troxerutin (1

  9. Divergent Perceptions of Barriers to Diabetic Retinopathy Screening Among Patients and Care Providers, Los Angeles, California, 2014–2015

    PubMed Central

    Lu, Yang; Serpas, Lilian; Genter, Pauline; Anderson, Betty; Campa, David

    2016-01-01

    Introduction Despite availability of screening for diabetic retinopathy, testing is underused by many low-income and racial/ethnic minority patients with diabetes. We examined perceived barriers to diabetic retinopathy screening among low-income patients and their health care providers and provider staffers. Methods We collected survey data from 101 patients with diabetes and 44 providers and staffers at a safety-net clinic where annual diabetic retinopathy screening rates were low. Barriers specified in the survey were derived from the literature. Results Patients surveyed (mean [standard deviation] age, 54.0 [7.7] y; 41% were male) were primarily Hispanics (70%) and African Americans (27%) of low socioeconomic status. Overall, 55% of patients received diabetic retinopathy screening in the previous year. Patients who could not explain why this screening is needed reported more barriers than patients who could (2.5 vs 1.4 barriers, P = .02). Fewer patients reported that they experienced barriers such as transportation (15%), language issues (15%), cultural beliefs or myths (4%), denial (8%), and fear (5%), which providers and staffers considered very or extremely important (all P < .001). Financial burdens (26%) and depression (22%) were most commonly reported by patients as barriers, yet providers and staffers did not rate these barriers as important, P < .001. Conclusion Patients and health care providers had markedly divergent perceptions of barriers to diabetic retinopathy screening. Patients with poor understanding of the need for screening were more likely to report such barriers. These results suggest a need for active community engagement to find key elements for education programs and other interventions to increase rates of diabetic retinopathy screening, particularly among low-income, minority populations. PMID:27710765

  10. A genome-wide linkage scan for diabetic retinopathy susceptibility genes in Mexican Americans with type 2 diabetes from Starr County, Texas.

    PubMed

    Hallman, D Michael; Boerwinkle, Eric; Gonzalez, Victor H; Klein, Barbara E K; Klein, Ronald; Hanis, Craig L

    2007-04-01

    We conducted a genome-wide linkage scan for genes contributing to retinopathy risk using 794 diabetes case subjects from 393 Mexican-American families from Starr County, Texas, having at least two diabetic siblings. The sample included 567 retinopathy case subjects comprising 282 affected sibling pairs. Retinopathy was classified as none, early nonproliferative, moderate-to-severe nonproliferative, or proliferative. Using 360 polymorphic markers (average spacing 9.4 cM), we conducted nonparametric linkage analysis followed by ordered-subset analysis (OSA) ranking families by average age of diabetes diagnosis. For any retinopathy, the highest LOD scores including all families were on chromosomes 3 (2.41 at 117 cM) and 12 (2.47 at 15.5). OSA logarithm of odds (LOD) scores >2 for any retinopathy occurred on chromosomes 12 (4.47 at 13.2 cM), 15 (3.65 at 100.6), and 20 (2.67 at 54.1). Scores >2 for either moderate-to-severe nonproliferative or proliferative retinopathy occurred on chromosomes 5 (2.53 at 11.2 cM), 6 (2.28 at 30.6), and 19 (2.21 at 100.6). Thus, unconditional linkage analysis revealed suggestive evidence of linkage with retinopathy on two chromosomes, whereas OSA revealed strong evidence of linkage on two chromosomes, and suggestive evidence on four. Candidate genes were identified in most implicated regions. PMID:17251272

  11. 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

  12. Influence of primary care practices on patients’ uptake of diabetic retinopathy screening: a qualitative case study

    PubMed Central

    Lindenmeyer, Antje; Sturt, Jackie A; Hipwell, Alison; Stratton, Irene M; al-Athamneh, Nidal; Gadsby, Roger; O’Hare, Joseph Paul; Scanlon, Peter H

    2014-01-01

    Background The NHS Diabetic Eye Screening Programme aims to reduce the risk of sight loss among people with diabetes in England by enabling prompt diagnosis of sight-threatening retinopathy. However, the rate of screening uptake between practices can vary from 55% to 95%. Existing research focuses on the impact of patient demographics but little is known about GP practice-related factors that can make a difference. Aim To identify factors contributing to high or low patient uptake of retinopathy screening. Design and setting Qualitative case-based study; nine purposively selected GP practices (deprived/affluent; high/low screening uptake) in three retinopathy screening programme areas. Methods Semi-structured interviews were conducted with patients, primary care professionals, and screeners. A comparative case-based analysis was carried out to identify factors related to high or low screening uptake. Results Eight possible factors that influenced uptake were identified. Five modifiable factors related to service and staff interactions: communication with screening services; contacting patients; integration of screening with other care; focus on the newly diagnosed; and perception of non-attenders. Three factors were non-modifiable challenges related to practice location: level of deprivation; diversity of ethnicities and languages; and transport and access. All practices adopted strategies to improve uptake, but the presence of two or more major barriers made it very hard for practices to achieve higher uptake levels. Conclusions A range of service-level opportunities to improve screening attendance were identified that are available to practices and screening teams. More research is needed into the complex interfaces of care that make up retinopathy screening. PMID:25071061

  13. 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

  14. 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

  15. High Prevalence of Lower Extremity Peripheral Artery Disease in Type 2 Diabetes Patients with Proliferative Diabetic Retinopathy

    PubMed Central

    Zhao, Dong; Yu, Cai-Guo; Xin, Zhong; Cao, Xi; Shi, Jing; Yang, Guang-Ran; Yuan, Ming-Xia; Yang, Jin-Kui

    2015-01-01

    Little is known about the relationship between lower extremity peripheral arterial disease (PAD) and proliferative diabetic retinopathy (PDR) in type 2 diabetes (T2D). Here, we explored the relationship between sight-threatening PDR and PAD. We screened for diabetic retinopathy (DR) and PAD in hospitalized patients with T2D. Patients with a diabetic duration of more than 10 years, HbA1c ≥7.5%, eGFR ≥60mL/min/1.73m2 and with PDR or with no diabetic retinopathy (NDR) were eligible for this cross-sectional study. Severities of DR were graded by digital retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. We assessed PAD by measuring Ankle Brachial Index (ABI), Toe Brachial Index (TBI) and Doppler ultrasound. Statistical analyses were performed using SPSS 17.0 software. Of the 1544 patients, 169 patients with extreme eye (57 PDR and 112 NDR) phenotypes met the inclusion criteria. Patients with PDR had a significantly higher proportion of low ABI (≤0.99) and high ABI (≥1.3) than patients with NDR (28.1% and 15.8% vs. 14.3% and 6.2% respectively, P<0.05). PDR patients also had lower TBI than NDR patients (0.56±0.09 vs. 0.61±0.08, P<0.01). The proportion of patients with abnormal duplex ultrasound was higher in PDR than in NDR (21.1% vs. 9.8%, P<0.001). This showed that PDR associated with PAD could be defined in multiple ways: abnormal ABI (≤0.9) (OR = 3.61, 95% CI: 1.15–11.26), abnormal TBI (OR = 2.84, 95% CI: 1.19–6.64), abnormal duplex (OR = 3.28, 95% CI: 1.00–10.71), and critical limb ischemia (OR = 5.52, 95% CI: 2.14–14.26). Moreover, PDR was a stronger independent correlation factor for PAD than a diabetic duration of 10 years. In conclusion, PAD is more common in PDR than in NDR. It implies that PDR and PAD are mostly concomitant in T2D. We should focus on screening PAD in patients with PDR in clinical practice. PMID:25822410

  16. Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A

    PubMed Central

    Yi, Quan-Yong; Deng, Gang; Chen, Nan; Bai, Zhi-Sha; Yuan, Jian-Shu; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun

    2016-01-01

    Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment. PMID:27725874

  17. 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

  18. [Transcranial magnetotherapy for the correction of initial manifestations of diabetic retinopathy in children].

    PubMed

    Nikolaeva, N V; Bolotova, N V; Kamenskikh, T G; Raĭgorodskiĭ, Iu M; Kolbenev, I O; Luk'ianov, V F

    2009-01-01

    This study included 45 children at the age from 5 to 17 years with type I diabetes mellitus complicated by diabetic retinopathy. All the patients showed retinal thickening at the macula and reduced amplitude of local electroretinogram suggesting compromised capillary circulation. The capillary blood flow was corrected by transcranial magnetotherapy with the use of an AMO-ATOS Ogolovie unit. The results of the treatment were evaluated from characteristics of laser Doppler flometry. A course of transcranial magnetotherapy comprising 10 daily seances resulted in a significant increase of microcirculation index, respiratory rhythm, and myogenic tone (by 1.64, 1.35, and 1.16 times respectively). In addition, morphometric and electrophysiological properties of the retina underwent positive changes. Transcranial exposure to the traveling magnetic field is recommended for the correction of intraocular microcirculation and prevention of diabetic macular oedema. PMID:19639694

  19. 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

  20. Current and future management of diabetic retinopathy: a personalized evidence-based approach

    PubMed Central

    Fante, Ryan J; Gardner, Thomas W; Sundstrom, Jeffrey M

    2014-01-01

    Summary Diabetic retinopathy (DR) is the leading cause of new-onset blindness in working-age individuals in the USA and represents a growing worldwide epidemic. Classic risk factors for onset or progression of DR include poor glycemic control, hypertension and hyperlipidemia; however, these factors account for only a small proportion of the risk of DR. New systemic risk factors are emerging, which may allow for personalized risk profiling and targeted treatment by physicians. In addition, early studies of vitreous fluid in patients with DR have resulted in a new paradigm: diabetes causes inflammation in the retina, which is mediated by multiple small signaling molecules that induce angiogenesis and vascular permeability. Future treatment of DR may involve two approaches: early vitreous analysis, followed by drug treatment targeted to the unique vitreous composition of the patient; and collaboration between ophthalmologists and primary care providers to address the unique systemic risk profile of each diabetic patient. PMID:24932222

  1. Effect of Intensive Diabetes Therapy on the Progression of Diabetic Retinopathy in Patients With Type 1 Diabetes: 18 Years of Follow-up in the DCCT/EDIC

    PubMed Central

    2015-01-01

    The Diabetes Control and Complications Trial (DCCT) demonstrated that a mean of 6.5 years of intensive therapy aimed at near-normal glucose levels reduced the risk of development and progression of retinopathy by as much as 76% compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications study (EDIC) observational follow-up showed that the risk of further progression of retinopathy 4 years after the DCCT ended was also greatly reduced in the former intensive group, despite nearly equivalent levels of HbA1c, a phenomenon termed metabolic memory. Metabolic memory was shown to persist through 10 years of follow-up. We now describe the risk of further progression of retinopathy, progression to proliferative diabetic retinopathy, clinically significant macular edema, and the need for intervention (photocoagulation or anti-VEGF) over 18 years of follow-up in EDIC. The cumulative incidence of each retinal outcome continues to be lower in the former intensive group. However, the year-to-year incidence of these outcomes is now similar, owing in large part to a reduction in risk in the former conventional treatment group. PMID:25204977

  2. Changing prevalence of retinopathy in newly diagnosed non-insulin dependent diabetes mellitus patients in Hong Kong.

    PubMed

    Wang, W Q; Ip, T P; Lam, K S

    1998-03-01

    In this retrospective study, the prevalence of chronic microangiopathic complications was determined in 474 Chinese patients with non-insulin dependent diabetes mellitus (NIDDM) who presented within 1 year of diagnosis to the diabetes clinic from January 1990 to December 1996. Mean age (+/- S.E.) was 53.6 (+/- 0.6) years. The overall prevalence of retinopathy was 21.9%. A significant increase was observed from 1990 to 1994 (P < 0.005), with the prevalence being 14.8, 13.0, 24.5, 32.3 and 35.4%, respectively, in consecutive years. A decreasing prevalence was seen from 1994 to 1996 (P < 0.001), being 8.2 and 7.4% in 1995 and 1996, respectively. A total of 95% of patients had nonproliferative retinopathy--proliferative retinopathy was found in 5% only. The overall prevalence of clinical nephropathy (proteinuria > 0.5 g/day) was 3.7%. Clinical neuropathy (increased vibration perception threshold) was found in 12.8% of patients. Patients with retinopathy and neuropathy were older (P < 0.0001 and P < 0.005, respectively) than those without the complications and systolic hypertension was more prevalent in patients with retinopathy (P < 0.05). In conclusion, a high prevalence of diabetic microangiopathic complications, especially of retinopathy, is present in newly diagnosed NIDDM patients in our population. It remains to be determined whether the changing prevalence of retinopathy at diagnosis bears any relationship to the increasing public awareness of diabetes and its complications in Hong Kong in recent years. Examination for chronic microangiopathic complications should be carried out in all newly diagnosed NIDDM patients.

  3. Development and Validation of a Diabetic Retinopathy Referral Algorithm Based on Single-Field Fundus Photography

    PubMed Central

    Srinivasan, Sangeetha; Shetty, Sharan; Natarajan, Viswanathan; Sharma, Tarun; Raman, Rajiv

    2016-01-01

    Purpose To develop a simplified algorithm to identify and refer diabetic retinopathy (DR) from single-field retinal images specifically for sight-threatening diabetic retinopathy for appropriate care (ii) to determine the agreement and diagnostic accuracy of the algorithm as a pilot study among optometrists versus “gold standard” (retinal specialist grading). Methods The severity of DR was scored based on colour photo using a colour coded algorithm, which included the lesions of DR and number of quadrants involved. A total of 99 participants underwent training followed by evaluation. Data of the 99 participants were analyzed. Fifty posterior pole 45 degree retinal images with all stages of DR were presented. Kappa scores (κ), areas under the receiver operating characteristic curves (AUCs), sensitivity and specificity were determined, with further comparison between working optometrists and optometry students. Results Mean age of the participants was 22 years (range: 19–43 years), 87% being women. Participants correctly identified 91.5% images that required immediate referral (κ) = 0.696), 62.5% of images as requiring review after 6 months (κ = 0.462), and 51.2% of those requiring review after 1 year (κ = 0.532). The sensitivity and specificity of the optometrists were 91% and 78% for immediate referral, 62% and 84% for review after 6 months, and 51% and 95% for review after 1 year, respectively. The AUC was the highest (0.855) for immediate referral, second highest (0.824) for review after 1 year, and 0.727 for review after 6 months criteria. Optometry students performed better than the working optometrists for all grades of referral. Conclusions The diabetic retinopathy algorithm assessed in this work is a simple and a fairly accurate method for appropriate referral based on single-field 45 degree posterior pole retinal images. PMID:27661981

  4. Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy

    PubMed Central

    Poulaki, Vassiliki; Joussen, Antonia M.; Mitsiades, Nicholas; Mitsiades, Constantine S.; Iliaki, Eirini F.; Adamis, Anthony P.

    2004-01-01

    Diabetic retinopathy is a leading cause of blindness in the Western world. Aberrant intercellular adhesion molecule-1 expression and leukocyte adhesion have been implicated in its pathogenesis, raising the possibility of an underlying chronic inflammatory mechanism. In the current study, the role of insulin-like growth factor (IGF)-I in these processes was investigated. We found that systemic inhibition of IGF-I signaling with a receptor-neutralizing antibody, or with inhibitors of PI-3 kinase (PI-3K), c-Jun kinase (JNK), or Akt, suppressed retinal Akt, JNK, HIF-1α, nuclear factor (NF)-κB, and AP-1 activity, vascular endothelial growth factor (VEGF) expression, as well as intercellular adhesion molecule-1 levels, leukostasis, and blood-retinal barrier breakdown, in a relevant animal model. Intravitreous administration of IGF-I increased retinal Akt, JNK, HIF-1α, NF-κB, and AP-1 activity, and VEGF levels. IGF-I stimulated VEGF promoter activity in vitro, mainly via HIF-1α, and secondarily via NF-κB and AP-1. In conclusion, IGF-I participates in the pathophysiology of diabetic retinopathy by inducing retinal VEGF expression via PI-3K/Akt, HIF-1α, NF-κB, and secondarily, JNK/AP-1 activation. Taken together, these in vitro and in vivo signaling studies thus identify potential targets for pharmacological intervention to preserve vision in patients with diabetes. PMID:15277220

  5. 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

  6. 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

  7. Robust detection and classification of longitudinal changes in color retinal fundus images for monitoring diabetic retinopathy.

    PubMed

    Narasimha-Iyer, Harihar; Can, Ali; Roysam, Badrinath; Stewart, Charles V; Tanenbaum, Howard L; Majerovics, Anna; Singh, Hanumant

    2006-06-01

    A fully automated approach is presented for robust detection and classification of changes in longitudinal time-series of color retinal fundus images of diabetic retinopathy. The method is robust to: 1) spatial variations in illumination resulting from instrument limitations and changes both within, and between patient visits; 2) imaging artifacts such as dust particles; 3) outliers in the training data; 4) segmentation and alignment errors. Robustness to illumination variation is achieved by a novel iterative algorithm to estimate the reflectance of the retina exploiting automatically extracted segmentations of the retinal vasculature, optic disk, fovea, and pathologies. Robustness to dust artifacts is achieved by exploiting their spectral characteristics, enabling application to film-based, as well as digital imaging systems. False changes from alignment errors are minimized by subpixel accuracy registration using a 12-parameter transformation that accounts for unknown retinal curvature and camera parameters. Bayesian detection and classification algorithms are used to generate a color-coded output that is readily inspected. A multiobserver validation on 43 image pairs from 22 eyes involving nonproliferative and proliferative diabetic retinopathies, showed a 97% change detection rate, a 3% miss rate, and a 10% false alarm rate. The performance in correctly classifying the changes was 99.3%. A self-consistency metric, and an error factor were developed to measure performance over more than two periods. The average self consistency was 94% and the error factor was 0.06%. Although this study focuses on diabetic changes, the proposed techniques have broader applicability in ophthalmology.

  8. Effect of focal laser photocoagulation in eyes with mild to moderate non-proliferative diabetic retinopathy

    PubMed Central

    Jeong, Seong Hun; Han, Jung Il; Cho, Sung Won; Lee, Dong Won; Kim, Chul Gu; Lee, Tae Gon; Kim, Jong Woo

    2016-01-01

    AIM To report the effect of focal laser photocoagulation on both the severity of hard exudates (HEs) and the rate of disease progression in eyes with mild to moderate non-proliferative diabetic retinopathy (NPDR). METHODS We retrospectively reviewed the medical records of 33 patients (60 eyes) who had been diagnosed with mild to moderate NPDR between January 2006 and December 2012. The patients were divided into 2 groups: Group A (38 eyes in 20 patients treated using focal laser photocoagulation) and Group B (treated without laser photocoagulation). We also reviewed the best corrected visual acuity measurements, and the fundus photographs taken at both baseline and follow-up visits. RESULTS In Group A, HE severity grade had decreased significantly from baseline to the final visit (P<0.05), but this was not the case in Group B (P=0.662). The cumulative probabilities of retinopathy progression at 5y were 26% in Group A and 30% in Group B. Kaplan-Meier survival curves showed no significant difference between the groups with regard to retinopathy progression (P=0.805). CONCLUSION Focal laser photocoagulation reduced the levels of HEs in eyes with mild to moderate NPDR. However, the treatment was not able to decelerate the progression of DR. PMID:27803861

  9. [Communication subsystem design of tele-screening system for diabetic retinopathy].

    PubMed

    Chen, Jian; Pan, Lin; Zheng, Shaohua; Yu, Lun

    2013-12-01

    A design scheme of a tele-screening system for diabetic retinopathy (DR) has been proposed, especially the communication subsystem. The scheme uses serial communication module consisting of ARM 7 microcontroller and relays to connect remote computer and fundus camera, and also uses C++ programming language based on MFC to design the communication software consisting of therapy and diagnostic information module, video/audio surveillance module and fundus camera control module. The scheme possesses universal property in some remote medical treatment systems which are similar to the system. PMID:24645585

  10. [Communication subsystem design of tele-screening system for diabetic retinopathy].

    PubMed

    Chen, Jian; Pan, Lin; Zheng, Shaohua; Yu, Lun

    2013-12-01

    A design scheme of a tele-screening system for diabetic retinopathy (DR) has been proposed, especially the communication subsystem. The scheme uses serial communication module consisting of ARM 7 microcontroller and relays to connect remote computer and fundus camera, and also uses C++ programming language based on MFC to design the communication software consisting of therapy and diagnostic information module, video/audio surveillance module and fundus camera control module. The scheme possesses universal property in some remote medical treatment systems which are similar to the system.

  11. 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.

  12. 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.

  13. [Does preoperative intravitreal bevacizumab reduce complications of vitrectomy for proliferative diabetic retinopathy?].

    PubMed

    Véliz, Daniela; Rada, Gabriel

    2014-12-12

    Proliferative diabetic retinopathy carries a high risk of blindness if it is not timely treated. The treatment many times includes vitrectomy. Bevacizumab, an anti-vascular endothelial growth factor, may decrease intraoperative complications. Searching in Epistemonikos database, which is maintained by screening 20 databases, we identified three systematic reviews including 9 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that bevacizumab probably decreases time and intraoperative bleeding, but there is uncertainty regarding its effects on visual acuity, and it might increase the risk of cardiovascular events.

  14. Retinal image analysis to detect and quantify lesions associated with diabetic retinopathy.

    PubMed

    Sánchez, C I; Hornero, R; López, M I; Poza, J

    2004-01-01

    An automatic method to detect hard exudates, a lesion associated with diabetic retinopathy, is proposed. The algorithm found on their color, using a statistical classification, and their sharp edges, applying an edge detector, to localize them. A sensitivity of 79.62% with a mean number of 3 false positives per image is obtained in a database of 20 retinal image with variable color, brightness and quality. In that way, we evaluate the robustness of the method in order to make adequate to a clinical environment. Further efforts will be done to improve its performance.

  15. Retinal image analysis to detect and quantify lesions associated with diabetic retinopathy.

    PubMed

    Sánchez, C I; Hornero, R; López, M I; Poza, J

    2004-01-01

    An automatic method to detect hard exudates, a lesion associated with diabetic retinopathy, is proposed. The algorithm found on their color, using a statistical classification, and their sharp edges, applying an edge detector, to localize them. A sensitivity of 79.62% with a mean number of 3 false positives per image is obtained in a database of 20 retinal image with variable color, brightness and quality. In that way, we evaluate the robustness of the method in order to make adequate to a clinical environment. Further efforts will be done to improve its performance. PMID:17272012

  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 between the ICAM-1 K469E polymorphism and diabetic retinopathy in Type 2 diabetes mellitus: a meta-analysis.

    PubMed

    Sun, Hongyan; Cong, Xianling; Sun, Ran; Wang, Chuanwen; Wang, Xue; Liu, Ya

    2014-05-01

    A meta-analysis was conducted to evaluate the association of ICAM-1 K469E gene polymorphism with diabetic retinopathy susceptibility in Type 2 diabetes mellitus. Seven studies involving 1094 cases and 909 controls were included. Current studies suggest that K469E polymorphism in ICAM-1 gene might not affect individual susceptibility to DR.

  18. 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

  19. Theoretical estimation of retinal oxygenation in chronic diabetic retinopathy.

    PubMed

    Olson, Jeffrey L; Asadi-Zeydabadi, Masoud; Tagg, Randall

    2015-03-01

    This paper uses computer modeling to estimate the progressive decline in oxygenation that occurs in the human diabetic retina after years of slowly progressive ischemic insult. An established model combines diffusion, saturable consumption, and blood capillary sources to determine the oxygen distribution across the retina. Incorporating long-term degradation of blood supply from the retinal capillaries into the model yields insight into the effects of progressive ischemia associated with prolonged hyperglycemia, suggesting time-scales over which therapeutic mitigation could have beneficial effect. A new extension of the model for oxygen distribution introduces a feedback mechanism for vasodilation and its potential to prolong healthy retinal function. PMID:25660722

  20. 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

  1. 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

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

    PubMed Central

    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

    2016-01-01

    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

  3. Noninvasive detection of microaneurysms in diabetic retinopathy by swept-source optical coherence tomography

    PubMed Central

    Cheng, Sarah; Leng, Theodore

    2016-01-01

    Background and objectives A method of identifying retinal vascular microaneurysms (MAs) in nonproliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography (SS-OCT). Patients and methods SS-OCT images were acquired in 17 eyes with NPDR using prototype SS-OCT device and fluorescein angiography (FA) images were obtained simultaneously. MAs identified on SS-OCT slabs were correlated to MAs identified on FA. Results MAs were identified in SS-OCT slabs in 15/17 eyes, resulting in NPDR diagnosis rate of 88%. Mean number of MAs identified on FA was 11.7±11.9 (total 199) and was 8.1±9.3 (total 137) on SS-OCT. Wilcoxon rank sum test showed no significant difference in MAs detected on SS-OCT and FA (P=0.2995) across eyes. Wilcoxon rank sum test showed SS-OCT detected slightly fewer MAs than FA per eye (3.65 less, P=0.0009). Conclusion SS-OCT visualization of MAs could serve as a tool for diagnosing NPDR, and possibly applied as an imaging biomarker for population-based diabetic retinopathy screening.

  4. A Web-based telemedicine system for diabetic retinopathy screening using digital fundus photography.

    PubMed

    Wei, Jack C; Valentino, Daniel J; Bell, Douglas S; Baker, Richard S

    2006-02-01

    The purpose was to design and implement a Web-based telemedicine system for diabetic retinopathy screening using digital fundus cameras and to make the software publicly available through Open Source release. The process of retinal imaging and case reviewing was modeled to optimize workflow and implement use of computer system. The Web-based system was built on Java Servlet and Java Server Pages (JSP) technologies. Apache Tomcat was chosen as the JSP engine, while MySQL was used as the main database and Laboratory of Neuro Imaging (LONI) Image Storage Architecture, from the LONI-UCLA, as the platform for image storage. For security, all data transmissions were carried over encrypted Internet connections such as Secure Socket Layer (SSL) and HyperText Transfer Protocol over SSL (HTTPS). User logins were required and access to patient data was logged for auditing. The system was deployed at Hubert H. Humphrey Comprehensive Health Center and Martin Luther King/Drew Medical Center of Los Angeles County Department of Health Services. Within 4 months, 1500 images of more than 650 patients were taken at Humphrey's Eye Clinic and successfully transferred to King/Drew's Department of Ophthalmology. This study demonstrates an effective architecture for remote diabetic retinopathy screening.

  5. Noninvasive detection of microaneurysms in diabetic retinopathy by swept-source optical coherence tomography

    PubMed Central

    Cheng, Sarah; Leng, Theodore

    2016-01-01

    Background and objectives A method of identifying retinal vascular microaneurysms (MAs) in nonproliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography (SS-OCT). Patients and methods SS-OCT images were acquired in 17 eyes with NPDR using prototype SS-OCT device and fluorescein angiography (FA) images were obtained simultaneously. MAs identified on SS-OCT slabs were correlated to MAs identified on FA. Results MAs were identified in SS-OCT slabs in 15/17 eyes, resulting in NPDR diagnosis rate of 88%. Mean number of MAs identified on FA was 11.7±11.9 (total 199) and was 8.1±9.3 (total 137) on SS-OCT. Wilcoxon rank sum test showed no significant difference in MAs detected on SS-OCT and FA (P=0.2995) across eyes. Wilcoxon rank sum test showed SS-OCT detected slightly fewer MAs than FA per eye (3.65 less, P=0.0009). Conclusion SS-OCT visualization of MAs could serve as a tool for diagnosing NPDR, and possibly applied as an imaging biomarker for population-based diabetic retinopathy screening. PMID:27695284

  6. 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

  7. Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy.

    PubMed

    Maharjan, Sony; Lee, Sujin; Agrawal, Vijayendra; Choi, Hyun-Jung; Maeng, Yong-Sun; Kim, Kyeojin; Kim, Nam-Jung; Suh, Young-Ger; Kwon, Young-Guen

    2011-04-25

    Endothelium integrity is important for the normal functioning of vessels, the disruption of which can lead to disease. The blood-retinal barrier required for normal retinal function is compromised in diabetic retinopathy, causing retinal vascular leakage. Previously, we demonstrated the ability of Sac-0601[((2R,3S)-3-acetoxy-6-((3S,10R,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxy)-3,6-dihydro-2H-pyran-2-yl)methyl acetate], a pseudo-sugar derivative of cholesterol, to increase survival of retinal endothelial cells. In the present study, we evaluated the ability of Sac-0601 to prevent retinal vascular leakages in vitro and in vivo. Sac-0601 treatment blocked VEGF-induced formation of actin stress fibers and stabilized the cortical actin ring in retinal endothelial cells. It also inhibited degradation of occludin, an important tight junction protein, and blocked VEGF-induced disruption of its linear pattern at the cell border. The [(14)C] sucrose permeability assay demonstrated that Sac-0601 was able to prevent VEGF-induced retinal endothelial permeability. The compound inhibited the vascular leakage in retina of mice intravitreally injected with VEGF. And it also significantly reduced the leakage in retina of diabetic retinopathy mice model. Taken together, our findings suggest the potential therapeutic usefulness of Sac-0601 for retinal vascular permeability diseases.

  8. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis

    PubMed Central

    2013-01-01

    Background Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Results Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). Conclusions The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10

  9. 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

  10. [Kallikrein-kinin system as a target for diabetic retinopathy treatment].

    PubMed

    Iarovaia, G A; Neshkova, E A; Blokhina, T B; Kochergin, S A; Vorob'eva, I V; Gigineishvili, D N

    2012-01-01

    Multifactor etiology of diabetic retinopathy (DR) determines difficulty of understanding of pathogenesis and need of search of effective approaches to study key mechanisms of development of this microvascular complication of diabetes mellitus (DM). Significant achievements of the last years show the contribution of two proteolytic systems into pathogenesis of DR, that control vascular tone and permeability - kallikrein-kinin (KKS) and renin-angiotensin systems (RAS). Among new approaches to DR treatment one of the most appropriate is an influence on KKS by means of inhibiting kallikrein, that leads to reduction of retinal vascular permeability and allows to prevent the development of macula oedema and other consequences of vascular wall damage in DR. PMID:22994115

  11. 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

  12. 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

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

    PubMed

    Chakravarthy, Harshini; Beli, Eleni; 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.

  14. 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

  15. Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications.

    PubMed

    Stem, Maxwell S; Gardner, Thomas W

    2013-01-01

    Diabetic retinopathy (DR), commonly classified as a microvascular complication of diabetes, is now recognized as a neurovascular complication or sensory neuropathy resulting from disruption of the neurovascular unit. Current therapies for DR target the vascular complication of the disease process, including neovascularization and diabetic macular edema. Since neurodegeneration is an early event in the pathogenesis of DR, it will be important to unravel the mechanisms that contribute to neuroretinal cell death in order to develop novel treatments for the early stages of DR. In this review we comment on how inflammation, the metabolic derangements associated with diabetes, loss of neuroprotective factors, and dysregulated glutamate metabolism may contribute to retinal neurodegeneration during diabetes. Promising potential therapies based on these specific aspects of DR pathophysiology are also discussed. Finally, we stress the importance of developing and validating new markers of visual function that can be used to shorten the duration of clinical trials and accelerate the delivery of novel treatments for DR to the public. PMID:23745549

  16. 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

  17. 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

  18. Fpga based hardware synthesis for automatic segmentation of retinal blood vessels in diabetic retinopathy images.

    PubMed

    Sivakamasundari, J; Kavitha, G; Sujatha, C M; Ramakrishnan, S

    2014-01-01

    Diabetic Retinopathy (DR) is a disorder that affects the structure of retinal blood vessels due to long-standing diabetes mellitus. Real-Time mass screening system for DR is vital for timely diagnosis and periodic screening to prevent the patient from severe visual loss. Human retinal fundus images are widely used for an automated segmentation of blood vessel and diagnosis of various blood vessel disorders. In this work, an attempt has been made to perform hardware synthesis of Kirsch template based edge detection for segmentation of blood vessels. This method is implemented using LabVIEW software and is synthesized in field programmable gate array board to yield results in real-time application. The segmentation of blood vessels using Kirsch based edge detection is compared with other edge detection methods such as Sobel, Prewitt and Canny. The texture features such as energy, entropy, contrast, mean, homogeneity and structural feature namely ratio of vessel to vessel free area are obtained from the segmented images. The performance of segmentation is analysed in terms of sensitivity, specificity and accuracy. It is observed from the results that the Kirsch based edge detection technique segmented the edges of blood vessels better than other edge detection techniques. The ratio of vessel to vessel free area classified the normal and DR affected retinal images more significantly than other texture based features. FPGA based hardware synthesis of Kirsch edge detection method is able to differentiate normal and diseased images with high specificity (93%). This automated segmentation of retinal blood vessels system could be used in computer-assisted diagnosis for diabetic retinopathy screening in real-time application.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Native American Ancestry Is Associated With Severe Diabetic Retinopathy in Latinos

    PubMed Central

    Gao, Xiaoyi; Gauderman, W. James; Marjoram, Paul; Torres, Mina; Chen, Yii-Der I.; Taylor, Kent D.; Rotter, Jerome I.; Varma, Rohit

    2014-01-01

    Purpose. Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Studies have observed that Latinos have a higher prevalence of DR than whites. The purpose of this study is to test the association between genetic admixture and severe DR in Latinos with type 2 diabetes mellitus (T2DM). Methods. We conducted a case–control study using 944 T2DM subjects from the Los Angeles Latino Eye Study. Cases (n = 135) were defined as proliferative or severe nonproliferative DR subjects. Controls (n = 809) were other diabetic subjects in the cohort. Genotyping was performed on the Illumina OmniExpress BeadChip. We estimated genetic ancestry in Latinos using STRUCTURE with the HapMap reference panels. Univariate and multivariate logistic regression analyses were used to test the relationship between the proportions of genetic ancestry and severe DR. Results. Native American ancestry (NAA) in Latino T2DM subjects is associated significantly with severe DR (P = 0.002). The association remained significant (P = 0.005) after adjusting for age, sex, duration of diabetes, hemoglobin A1c, body mass index, systolic blood pressure, education, and income. We also validated the NAA estimates in Latinos using ADMIXTURE with the 1000 Genomes Project reference panels and obtained consistent results. Conclusions. Our results demonstrate for the first time to our knowledge that NAA is a significant risk factor for severe DR in Latinos. PMID:25146985

  4. A hemochromatosis-causing mutation C282Y is a risk factor for proliferative diabetic retinopathy in Caucasians with type 2 diabetes.

    PubMed

    Peterlin, Borut; Globocnik Petrovic, Mojca; Makuc, Jana; Hawlina, Marko; Petrovic, Daniel

    2003-01-01

    Iron metabolism might be involved in the pathogenesis of type 2 diabetes and in the pathogenesis of diabetic retinopathy. C282Y and H63D mutations in the hemochromatosis (HFE) gene are associated with increased serum iron levels and consequently with hereditary hemochromatosis. In the present study, we searched for a relationship between C282Y and H63D gene mutations and the development of proliferative diabetic retinopathy in Caucasians with type 2 diabetes. For this purpose, 90 subjects with type 2 diabetes with proliferative diabetic retinopathy (PDR) were compared to 133 diabetic subjects without PDR. There was a significantly higher frequency of the C282Y heterozygotes in patients with PDR compared to subjects without it (OR=3.0, 95% CI=1.2-8.0; p=0.02), whereas no association was demonstrated between PDR and H63D genotypes (OR=1.1, 95% CI=0.6-2.2; p=0.7). Logistic regression analysis revealed that the C282Y mutation was a significant independent risk factor for the development of PDR (OR=6.1, 95% CI=1.2-30.5; p=0.027). These data suggest that heterozygosity for C282Y might be a novel risk factor for PDR in Caucasians with type 2 diabetes. PMID:14618419

  5. 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

  6. A computational-intelligence-based approach for detection of exudates in diabetic retinopathy images.

    PubMed

    Osareh, Alireza; Shadgar, Bita; Markham, Richard

    2009-07-01

    Currently, there is an increasing interest for setting up medical systems that can screen a large number of people for sight threatening diseases, such as diabetic retinopathy. This paper presents a method for automated identification of exudate pathologies in retinopathy images based on computational intelligence techniques. The color retinal images are segmented using fuzzy c-means clustering following some preprocessing steps, i.e., color normalization and contrast enhancement. The entire segmented images establish a dataset of regions. To classify these segmented regions into exudates and nonexudates, a set of initial features such as color, size, edge strength, and texture are extracted. A genetic-based algorithm is used to rank the features and identify the subset that gives the best classification results. The selected feature vectors are then classified using a multilayer neural network classifier. The algorithm was implemented using a large image dataset consisting of 300 manually labeled retinal images, and could identify affected retinal images with 96.0% sensitivity while it recognized 94.6% of the normal images, i.e., the specificity. Moreover, the proposed scheme illustrated an accuracy including 93.5% sensitivity and 92.1% predictivity for identification of retinal exudates at the pixel level.

  7. Reduced levels of brain derived neurotrophic factor (BDNF) in the serum of diabetic retinopathy patients and in the retina of diabetic rats.

    PubMed

    Ola, M Shamsul; Nawaz, Mohd Imtiaz; El-Asrar, Ahmed Abu; Abouammoh, Marwan; Alhomida, Abdullah S

    2013-04-01

    Diabetic retinopathy (DR) is widely recognized as a neurovascular disease. Retina, being a neuronal tissue of the eye, produces neurotrophic factors for its maintenance. However, diabetes dysregulates their levels and thereby may damage the retina. Among neurotrophins, brain derived neurotrophic factor (BDNF) is the most abundant in the retina. In this study, we investigated the level of BDNF in the serum of patients with DR and also in the serum and retina of streptozotocin-induced diabetic rats. The level of BDNF was significantly decreased in the serum of proliferative diabetic retinopathy patients as compared to that of non-diabetic healthy controls (25.5 ± 8.5-10.0 ± 8.1 ng/ml, p < 0.001) as well as compared to that of diabetic patients with no retinopathy (21.8 ± 4.7-10.0 ± 8.1 ng/ml, p < 0.001), as measured by ELISA techniques. The levels of BDNF in the serum and retina of diabetic rats were also significantly reduced compared to that of non-diabetic controls (p < 0.05). In addition, the expression level of tropomyosin-related kinase B (TrkB) was significantly decreased in diabetic rat retina compared to that of non-diabetic controls as determined by Western blotting technique. Caspase-3 activity was increased in diabetic rat retina after 3 weeks of diabetes and remained elevated until 10 weeks, which negatively correlated with the level of BDNF (r = -0.544, p = 0.013). Our results indicate that reduced levels of BDNF in diabetes may cause apoptosis and neurodegeneration early in diabetic retina, which may lead to neuro-vascular damage later in DR. PMID:23271640

  8. 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

  9. An Active Learning Classifier for Further Reducing Diabetic Retinopathy Screening System Cost

    PubMed Central

    An, Mingqiang

    2016-01-01

    Diabetic retinopathy (DR) screening system raises a financial problem. For further reducing DR screening cost, an active learning classifier is proposed in this paper. Our approach identifies retinal images based on features extracted by anatomical part recognition and lesion detection algorithms. Kernel extreme learning machine (KELM) is a rapid classifier for solving classification problems in high dimensional space. Both active learning and ensemble technique elevate performance of KELM when using small training dataset. The committee only proposes necessary manual work to doctor for saving cost. On the publicly available Messidor database, our classifier is trained with 20%–35% of labeled retinal images and comparative classifiers are trained with 80% of labeled retinal images. Results show that our classifier can achieve better classification accuracy than Classification and Regression Tree, radial basis function SVM, Multilayer Perceptron SVM, Linear SVM, and K Nearest Neighbor. Empirical experiments suggest that our active learning classifier is efficient for further reducing DR screening cost. PMID:27660645

  10. An Active Learning Classifier for Further Reducing Diabetic Retinopathy Screening System Cost

    PubMed Central

    An, Mingqiang

    2016-01-01

    Diabetic retinopathy (DR) screening system raises a financial problem. For further reducing DR screening cost, an active learning classifier is proposed in this paper. Our approach identifies retinal images based on features extracted by anatomical part recognition and lesion detection algorithms. Kernel extreme learning machine (KELM) is a rapid classifier for solving classification problems in high dimensional space. Both active learning and ensemble technique elevate performance of KELM when using small training dataset. The committee only proposes necessary manual work to doctor for saving cost. On the publicly available Messidor database, our classifier is trained with 20%–35% of labeled retinal images and comparative classifiers are trained with 80% of labeled retinal images. Results show that our classifier can achieve better classification accuracy than Classification and Regression Tree, radial basis function SVM, Multilayer Perceptron SVM, Linear SVM, and K Nearest Neighbor. Empirical experiments suggest that our active learning classifier is efficient for further reducing DR screening cost.

  11. 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

  12. 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

  13. The association of hematologic inflammatory markers with atherogenic index in type 2 diabetic retinopathy patients

    PubMed Central

    Akdoğan, Müberra; Ustundag-Budak, Yasemin; Huysal, Kagan

    2016-01-01

    Background Atherogenic dyslipidemia is particularly common in people with type 2 diabetes (DM2). Platelets from patients with DM2 have increased reactivity and baseline activation. The aim of the present study is to evaluate the relationship between atherogenic index and hematologic inflammatory markers and to evaluate the relationship between these parameters and associated variables in diabetic retinopathy (DR) patients. Methods The medical records of all patients admitted to the eye clinic between January and December 2014 were evaluated systematically. Laboratory parameters of 278 outpatients with DM2 diagnosed after the age of 30 years and 107 healthy subjects were analyzed. Results The DM2 + DR group consisted of 120 patients (47 males and 73 females; mean age 59.8±9.2 years). The DM2 without DR group consisted of 158 patients (59 males and 99 females; mean age 57.3±12.2 years). Mean platelet volume, platelet distribution width (PDW), platelet–lymphocyte (P/L) ratio, triglycerides, and atherogenic index were higher in DM2 patients than in control patients, but there was no difference between the DM2 + DR and the DM2 without DR groups. Only P/L ratio was different in the DM2 + DR patients compared to the DM2 without DR patients. Hemoglobin A1c levels correlated very weakly with the mean platelet volume, PDW, P/L ratio, and the red cell distribution width. The atherogenic index was very weakly correlated with the P/L ratio, PDW, and red cell distribution width. Conclusion Dyslipidemia-induced inflammation contributes to pathological processes that lead to retinopathy in DR patients. PMID:27695285

  14. The association of hematologic inflammatory markers with atherogenic index in type 2 diabetic retinopathy patients

    PubMed Central

    Akdoğan, Müberra; Ustundag-Budak, Yasemin; Huysal, Kagan

    2016-01-01

    Background Atherogenic dyslipidemia is particularly common in people with type 2 diabetes (DM2). Platelets from patients with DM2 have increased reactivity and baseline activation. The aim of the present study is to evaluate the relationship between atherogenic index and hematologic inflammatory markers and to evaluate the relationship between these parameters and associated variables in diabetic retinopathy (DR) patients. Methods The medical records of all patients admitted to the eye clinic between January and December 2014 were evaluated systematically. Laboratory parameters of 278 outpatients with DM2 diagnosed after the age of 30 years and 107 healthy subjects were analyzed. Results The DM2 + DR group consisted of 120 patients (47 males and 73 females; mean age 59.8±9.2 years). The DM2 without DR group consisted of 158 patients (59 males and 99 females; mean age 57.3±12.2 years). Mean platelet volume, platelet distribution width (PDW), platelet–lymphocyte (P/L) ratio, triglycerides, and atherogenic index were higher in DM2 patients than in control patients, but there was no difference between the DM2 + DR and the DM2 without DR groups. Only P/L ratio was different in the DM2 + DR patients compared to the DM2 without DR patients. Hemoglobin A1c levels correlated very weakly with the mean platelet volume, PDW, P/L ratio, and the red cell distribution width. The atherogenic index was very weakly correlated with the P/L ratio, PDW, and red cell distribution width. Conclusion Dyslipidemia-induced inflammation contributes to pathological processes that lead to retinopathy in DR patients.

  15. Novel drugs and their targets in the potential treatment of diabetic retinopathy

    PubMed Central

    Nawaz, Mohd Imtiaz; Abouammoh, Marwan; Khan, Haseeb A.; Alhomida, Abdullah S.; Alfaran, Mubarak F.; Ola, Mohammad Shamsul

    2013-01-01

    Diabetic retinopathy (DR) is the most common complication of diabetes. It causes vision loss, and the incidence is increasing with the growth of the diabetes epidemic worldwide. Over the past few decades a number of clinical trials have confirmed that careful control of glycemia and blood pressure can reduce the risk of developing DR and control its progression. In recent years, many treatment options have been developed for clinical management of the complications of DR (e.g., proliferative DR and macular edema) using laser-based therapies, intravitreal corticosteroids and anti-vascular endothelial growth factors, and vitrectomy to remove scarring and hemorrhage, but all these have limited benefits. In this review, we highlight and discuss potential molecular targets and new approaches that have shown great promise for the treatment of DR. New drugs and strategies are based on targeting a number of hyperglycemia-induced metabolic stress pathways, oxidative stress and inflammatory pathways, the renin-angiotensin system, and neurodegeneration, in addition to the use of stem cells and ribonucleic acid interference (RNAi) technologies. At present, clinical trials of some of these newer drugs in humans are yet to begin or are in early stages. Together, the new therapeutic drugs and approaches discussed may control the incidence and progression of DR with greater efficacy and safety. PMID:23619778

  16. 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.

  17. The Effect of Bariatric Surgery on Diabetic Retinopathy: Good, Bad, or Both?

    PubMed Central

    Gorman, Dora M.; le Roux, Carel W.

    2016-01-01

    Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive. PMID:27766242

  18. Modulation of diabetic retinopathy pathophysiology by natural medicines through PPAR-γ-related pharmacology

    PubMed Central

    Song, Min K; Roufogalis, Basil D; Huang, Tom H W

    2012-01-01

    Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and remains a major cause of preventable blindness among adults at working age. DR involves an abnormal pathology of major retinal cells, including retinal pigment epithelium, microaneurysms, inter-retinal oedema, haemorrhage, exudates (hard exudates) and intraocular neovascularization. The biochemical mechanisms associated with hyperglycaemic-induced DR are through multifactorial processes. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in the pathogenesis of DR by inhibiting diabetes-induced retinal leukostasis and leakage. Despite DR causing eventual blindness, only a few visual or ophthalmic symptoms are observed until visual loss develops. Therefore, early medical interventions and prevention are the current management strategies. Laser photocoagulation therapy is the most common treatment. However, this therapy may cause retinal damage and scarring. Herbal and traditional natural medicines may provide an alternative to prevent or delay the progression of DR. This review provides an analysis of the therapeutic potential of herbal and traditional natural medicines or their active components for the slowdown of progression of DR and their possible mechanism through the PPAR-γ pathway. LINKED ARTICLE This article is commented on by Costa and Ciccodicola, pp. 1–3 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01443.x PMID:21480863

  19. 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

  20. 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

  1. 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

  2. Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers.

    PubMed

    Torok, Zsolt; Peto, Tunde; Csosz, Eva; Tukacs, Edit; Molnar, Agnes M; Berta, Andras; Tozser, Jozsef; Hajdu, Andras; Nagy, Valeria; Domokos, Balint; Csutak, Adrienne

    2015-01-01

    Background. It is estimated that 347 million people suffer from diabetes mellitus (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The progression of DR can be slowed down with early diagnosis and treatment. Therefore our aim was to develop a novel automated method for DR screening. Methods. 52 patients with diabetes mellitus were enrolled into the project. Of all patients, 39 had signs of DR. Digital retina images and tear fluid samples were taken from each eye. The results from the tear fluid proteomics analysis and from digital microaneurysm (MA) detection on fundus images were used as the input of a machine learning system. Results. MA detection method alone resulted in 0.84 sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87 sensitivity and 0.68 specificity values were achieved. The combined data analysis integrated the features of the proteomics data along with the number of detected MAs in the associated image and achieved sensitivity/specificity values of 0.93/0.78. Conclusions. As the two different types of data represent independent and complementary information on the outcome, the combined model resulted in a reliable screening method that is comparable to the requirements of DR screening programs applied in clinical routine.

  3. Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers

    PubMed Central

    Torok, Zsolt; Peto, Tunde; Csosz, Eva; Tukacs, Edit; Molnar, Agnes M.; Berta, Andras; Tozser, Jozsef; Hajdu, Andras; Nagy, Valeria; Domokos, Balint; Csutak, Adrienne

    2015-01-01

    Background. It is estimated that 347 million people suffer from diabetes mellitus (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The progression of DR can be slowed down with early diagnosis and treatment. Therefore our aim was to develop a novel automated method for DR screening. Methods. 52 patients with diabetes mellitus were enrolled into the project. Of all patients, 39 had signs of DR. Digital retina images and tear fluid samples were taken from each eye. The results from the tear fluid proteomics analysis and from digital microaneurysm (MA) detection on fundus images were used as the input of a machine learning system. Results. MA detection method alone resulted in 0.84 sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87 sensitivity and 0.68 specificity values were achieved. The combined data analysis integrated the features of the proteomics data along with the number of detected MAs in the associated image and achieved sensitivity/specificity values of 0.93/0.78. Conclusions. As the two different types of data represent independent and complementary information on the outcome, the combined model resulted in a reliable screening method that is comparable to the requirements of DR screening programs applied in clinical routine. PMID:26221613

  4. 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

  5. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A–dependent eNOS inactivation

    PubMed Central

    García, Celina; Aranda, Jorge; Arnold, Edith; Thébault, Stéphanie; Macotela, Yazmín; López-Casillas, Fernando; Mendoza, Valentín; Quiroz-Mercado, Hugo; Hernández-Montiel, Hebert Luis; Lin, Sue-Hwa; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2008-01-01

    Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies. PMID:18497878

  6. 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

  7. 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

  8. Low-Intensity Far-Red Light Inhibits Early Lesions That Contribute to Diabetic Retinopathy: In Vivo and In Vitro

    PubMed Central

    Tang, Johnny; Du, Yunpeng; Lee, Chieh Allen; Talahalli, Ramaprasad; Eells, Janis T.; Kern, Timothy S.

    2013-01-01

    Purpose. Treatment with light in the far-red to near-infrared region of the spectrum (photobiomodulation [PBM]) has beneficial effects in tissue injury. We investigated the therapeutic efficacy of 670-nm PBM in rodent and cultured cell models of diabetic retinopathy. Methods. Studies were conducted in streptozotocin-induced diabetic rats and in cultured retinal cells. Diabetes-induced retinal abnormalities were assessed functionally, biochemically, and histologically in vivo and in vitro. Results. We observed beneficial effects of PBM on the neural and vascular elements of retina. Daily 670-nm PBM treatment (6 J/cm2) resulted in significant inhibition in the diabetes-induced death of retinal ganglion cells, as well as a 50% improvement of the ERG amplitude (photopic b wave responses) (both P < 0.01). To explore the mechanism for these beneficial effects, we examined physiologic and molecular changes related to cell survival, oxidative stress, and inflammation. PBM did not alter cytochrome oxidase activity in the retina or in cultured retinal cells. PBM inhibited diabetes-induced superoxide production and preserved MnSOD expression in vivo. Diabetes significantly increased both leukostasis and expression of ICAM-1, and PBM essentially prevented both of these abnormalities. In cultured retinal cells, 30-mM glucose exposure increased superoxide production, inflammatory biomarker expression, and cell death. PBM inhibited all of these abnormalities. Conclusions. PBM ameliorated lesions of diabetic retinopathy in vivo and reduced oxidative stress and cell death in vitro. PBM has been documented to have minimal risk. PBM is noninvasive, inexpensive, and easy to administer. We conclude that PBM is a simple adjunct therapy to attenuate the development of diabetic retinopathy. PMID:23557732

  9. 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

  10. 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

  11. 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

  12. A Simple Risk Stratification for Time to Development of Sight-Threatening Diabetic Retinopathy

    PubMed Central

    Stratton, Irene M.; Aldington, Stephen J.; Taylor, David J.; Adler, Amanda I.; Scanlon, Peter H.

    2013-01-01

    OBJECTIVE The American Diabetes Association and the English NHS Diabetic Eye Screening Program recommend annual screening for diabetic retinopathy (DR) with referral to ophthalmology clinics of patients with sight-threatening DR (STDR). Using only longitudinal data from retinal photographs in the population-based NHS Diabetic Eye Screening Program in Gloucestershire, we developed a simple means to estimate risk of STDR. RESEARCH DESIGN AND METHODS From 2005, 14,554 patients with no DR or mild nonproliferative DR only at two consecutive annual digital photographic screenings were categorized by the presence of DR in neither, one, or both eyes at each screening and were followed for a further median 2.8 years. RESULTS Of 7,246 with no DR at either screening, 120 progressed to STDR, equivalent to an annual rate of 0.7%. Of 1,778 with no DR in either eye at first screening and in one eye at second screening, 80 progressed to STDR, equivalent to an annual rate of 1.9% and to a hazard ratio (HR) of 2.9 (95% CI 2.2–3.8) compared with those with no DR. Of 1,159 with background DR in both eyes at both screenings, 299 progressed to STDR equivalent to an annual rate of 11% and an HR of 18.2 (14.7–22.5) compared with individuals with no DR. CONCLUSIONS Combining the results from 2 consecutive years of photographic screening enables estimation of the risk of future development of STDR. In countries with systematic screening programs, these results could inform decisions about screening frequency. PMID:23150285

  13. A Potential Role for Angiopoietin 2 in the Regulation of the Blood–Retinal Barrier in Diabetic Retinopathy

    PubMed Central

    Rangasamy, Sampathkumar; Srinivasan, Ramprasad; Maestas, Joann; Das, Arup

    2011-01-01

    Purpose. Although VEGF has been identified as an important mediator of the blood–retinal barrier alteration in diabetic retinopathy, the hypothesis for this study was that that other molecules, including the angiopoietins (Ang-1 and -2), may play a role. The expression of angiopoietins was analyzed in an animal model of diabetic retinopathy, and the role of Ang-2 in the regulation of diabetes-induced alterations of vascular permeability was characterized. Methods. Diabetes was induced in rats, and human retinal endothelial cells (HRECs) were grown in media with 5.5 or 30.5 mM glucose. Levels of Ang-1 and -2 mRNA and protein were analyzed. Fluorescence-based assays were used to assess the effect of Ang-2 on vascular permeability in vivo and in vitro. The effect of Ang-2 on VE-cadherin function was assessed by measuring the extent of tyrosine phosphorylation. Results. Ang-2 mRNA and protein increased in the retinal tissues after 8 weeks of diabetes and in high-glucose–treated cells. Intravitreal injection of Ang-2 in rats produced a significant increase in retinal vascular permeability. Ang-2 increased HREC monolayer permeability that was associated with a decrease in VE-cadherin and a change in monolayer morphology. High glucose and Ang-2 produced a significant increase in VE-cadherin phosphorylation. Conclusions. Ang-2 is upregulated in the retina in an animal model of diabetes, and hyperglycemia induces the expression of Ang-2 in isolated retinal endothelial cells. Increased Ang-2 alters VE-cadherin function, leading to increased vascular permeability. Thus, Ang-2 may play an important role in increased vasopermeability in diabetic retinopathy. PMID:21310918

  14. 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

  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. 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

  17. 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.

  18. Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat.

    PubMed

    Amadio, Marialaura; Pascale, Alessia; Cupri, Sarha; Pignatello, Rosario; Osera, Cecilia; D'Agata, Velia; D'Amico, Agata Grazia; Leggio, Gian Marco; Ruozi, Barbara; Govoni, Stefano; Drago, Filippo; Bucolo, Claudio

    2016-09-01

    We evaluated whether specifically and directly targeting human antigen R (HuR), a member of embryonic lethal abnormal vision (ELAV) proteins family, may represent a new potential therapeutic strategy to manage diabetic retinopathy. Nanosystems loaded with siRNA silencing HuR expression (lipoplexes), consisting of solid lipid nanoparticles (SLN) and liposomes (SUV) were prepared. Photon correlation spectroscopy analysis, Zeta potential measurement and atomic force microscopy (AFM) studies were carried out to characterize the complexation of siRNA with the lipid nanocarriers. Nanosystems were evaluated by using AFM and scanning electron microscopy. The lipoplexes were injected into the eye of streptozotocin (STZ)-induced diabetic rats. Retinal HuR and VEGF levels were detected by Western blot and ELISA, respectively. Retinal histology was also carried out. The results demonstrated that retinal HuR and VEGF are significantly increased in STZ-rats and are blunted by HuR siRNA treatment. Lipoplexes with a weak positive surface charge and with a 4:1 N/P (cationic lipid nitrogen to siRNA phosphate) ratio exert a better transfection efficiency, significantly dumping retinal HuR and VEGF levels. In conclusion, we demonstrated that siRNA can be efficiently delivered into the rat retina using lipid-based nanocarriers, and some of the lipoplexes loaded with siRNA silencing HuR expression are potential candidates to manage retinal diseases.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy.

    PubMed

    Yamagishi, S; Takeuchi, M; Inagaki, Y; Nakamura, K; Imaizumi, T

    2003-01-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic derangements. In this review, we discuss the molecular mechanisms of diabetic retinopathy and nephropathy, especially focusing on advanced glycation end products (AGEs) and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in diseases, including diabetic microangiopathy, will be discussed in the next review article. PMID:15224502

  4. 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

  5. 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

  6. 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

  7. Evaluation of geometric features as biomarkers of diabetic retinopathy for characterizing the retinal vascular changes during the progression of diabetes.

    PubMed

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

    2015-01-01

    Diabetic retinopathy (DR) has been widely studied and characterized. However, until now, it is unclear how different features, extracted from the retinal vasculature, can be associated with the progression of diabetes and therefore become biomarkers of DR. In this study, a comprehensive analysis is presented, in which four groups were created, using eighty fundus images from twenty patients, who have progressed to DR and they had no history of any other diseases (e.g. hypertension or glaucoma). The significance of the following features was evaluated: widths, angles, branching coefficient (BC), angle-to-BC ratio, standard deviations, means and medians of widths and angles, fractal dimension (FD), lacunarity and FD-to-lacunarity ratio, using a mixed model analysis of variance (ANOVA) design. All the features were measured from the same junctions of each patient, using an automated tool. The discriminative power of these features was evaluated, using decision trees and random forests classifiers. Cross validation and out-of-bag error were used to evaluate the classifiers' performance, calculating the area under the ROC curve (AUC) and the classification error. Widths, FD and FD-to-Lacunarity ratio were found to differ significantly. Random forests had a superior performance of 0.768 and 0.737 in the AUC for the two cases of classification, namely three-years-pre-DR/post-DR and two-years-pre-DR/post-DR respectively.

  8. 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.

  9. Different determinants of neovascularization on the optic disc and on the retina in patients with severe nonproliferative diabetic retinopathy.

    PubMed

    Valsania, P; Warram, J H; Rand, L I; Krolewski, A S

    1993-02-01

    Almost all patients with type I and many with type II diabetes develop proliferative retinopathy. This entity consists of two components: new blood vessels on the optic disc (NVD), which frequently lead to visual loss, and new blood vessels elsewhere on the retina (NVE), which do not pose such a serious threat to vision. This study examined determinants of neovascularization specifically on the optic disc in eyes with severe nonproliferative retinopathy. The study eyes were under surveillance as the untreated control eyes of participants in the Diabetic Retinopathy Study. During the 5-year follow-up period, NVE developed in almost all of the eyes, whereas the cumulative incidence of NVD in these same eyes was 64% and varied according to several factors. The risk of NVD in a study eye was increased if the contralateral treated eye had NVD rather than NVE or severe nonproliferative retinopathy (odds ratio [OR], 6.1; P < .0001). It was also increased if the study eye had, at the baseline examination, soft exudates and intraretinal microvascular abnormalities (OR, 5.7; P = .002) or soft exudates alone (OR, 4.0; P = .04). Nephropathy and poor glycemic control were each associated with a two-fold increase in risk but neither was statistically significant. Eyes of individuals over 40 years of age were protected from the development of NVD (OR, 0.5; P < .05). The findings of this study support the hypothesis that, in patients with diabetes, the development of NVD is determined by different factors than the development of NVE.

  10. Low plasma levels of brain derived neurotrophic factor are potential risk factors for diabetic retinopathy in Chinese type 2 diabetic patients.

    PubMed

    Liu, Shao-Yi; Du, Xiao-Fang; Ma, Xiang; Guo, Jian-Lian; Lu, Jian-Min; Ma, Lu-Sheng

    2016-01-15

    Previous studies suggested that neurotrophins play a role in the diabetic retinopathy (DR). We therefore evaluated the role of plasma brain derived neurotrophic factor (BDNF) levels in Chinese type 2 diabetic patients with and without diabetic retinopathy (DR). Plasma levels of BDNF were determined in type 2 diabetic patients (N=344). At baseline, the demographical and clinical data were taken. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic curves (ROC) was used to test the overall predict accuracy of BDNF and other markers. Diabetic patients with DR and vision-threatening diabetic retinopathy (VTDR) had significantly lower BDNF levels on admission (P<0.0001 both). BDNF improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.76 (95% confidence interval [CI], 0.71-0.82) to 0.89 (95% CI, 0.82-0.95; P<0.01) and for VDTR from 0.84 (95% CI, 0.78-0.92) to 0.95 (95% CI, 0.90-0.98; P<0.01). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma BDNF levels≤12.4 ng/mL(1(rd) quartiles) was an independent marker of DR (OR=3.92; 95%CI: 2.31-6.56) and VTDR (OR=4.88; 95%CI: 2.21-9.30). The present study demonstrated that decreased plasma levels of BDNF were independent markers for DR and VDTR in Chinese type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.

  11. Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways

    PubMed Central

    Aldebasi, Yousef H; Aly, Salah M; Rahmani, Arshad H

    2013-01-01

    Diabetic Retinopathy (DR) is one of the most common complications of diabetes mellitus that affects the blood vessels of the retina, leading to blindness. The current approach of treatment based on anti-inflammatory, anti-angiogenesis drugs and laser photocoagulation are effective but also shows adverse affect in retinal tissues and that can even worsen the visual abilities. Thus, a safe and effective mode of treatment is needed to control or delaying the DR. Based on the earlier evidence of the potentiality of natural products as anti-oxidants, anti-diabetic and antitumor, medicinal plants may constitute a good therapeutic approach in the prevention of DR. Curcumin, constituents of dietary spice turmeric, has been observed to have therapeutic potential in the inhibition or slow down progression of DR. In this review, we summarize the therapeutic potentiality of curcumin in the delaying the DR through antioxidant, anti-inflammatory, inhibition of Vascular Endothelial Growth and nuclear transcription factors. The strength of involvement of curcumin in the modulation of genes action creates a strong optimism towards novel therapeutic strategy of diabetic retinopathy and important mainstay in the management of diabetes and its complications DR. PMID:24379904

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. [The role of vascular endothelial growth factor in angiogenesis and diabetic retinopathy].

    PubMed

    Valiatti, Fabiana Borba; Crispim, Daisy; Benfica, Camila; Valiatti, Bruna Borba; Kramer, Caroline K; Canani, Luís Henrique

    2011-03-01

    Diabetic retinopathy (DR), a DM microvascular complication, is the leading cause of blindness. Angiogenic factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of DR. VEGF-A is a potent, multifunctional cytokine that acts through the receptors VEGFR-1 and VEGFR-2 expressed in the vascular endothelium and causing increased vascular permeability and neovascularization stimulation in both physiological and pathological processes. The expression of VEGFR-1 is upregulated by hypoxia and is less responsive to VEGF compared to VEGFR-2 which is the main mediator mitogenic, angiogenic, and increased vascular permeability. VEGF polymorphisms have been studied in DR susceptibility and progression. Significant association between the polymorphism 634C / G and the presence of RD is reported mainly in relation to allele C. The homozygous CC is associated to proliferative RD and to increased vitreous and serum levels of VEGF suggesting that the presence of the C allele is an independent risk factor for RD. The knowledge of VEGF lead to the development of anti-VEGF drugs (pegaptanib, ranibizumab and bevacizumab) aiming to prevent pathological neovascularization. The anti-VEGF therapy is a reality in practice medical treatment of DR. PMID:21584427

  2. 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

  3. Combined Tractional and Rhegmatogenous Retinal Detachment in Proliferative Diabetic Retinopathy in the Anti-VEGF Era

    PubMed Central

    Hsieh, Yi-Ting; Yang, Chung-May

    2014-01-01

    Purpose. To investigate the clinical features, surgical outcomes, and prognostic factors of combined rhegmatogenous and tractional detachment (combined RD) in proliferative diabetic retinopathy (PDR) in recent years. Methods. Medical records of PDR and combined RD treated with vitrectomy from 2008 to 2013 were retrospectively reviewed. Results. A total of 57 eyes from 49 patients were included. Nine eyes had received panretinal photocoagulation (PRP) and 7 eyes had intravitreal bevacizumab (IVB) within 3 months before RD developed. Thirty-eight eyes (66.7%) had ≧3 sites of broad adhesion of fibrovascular proliferation (FVP). Thirty-three eyes (57.9%) showed active FVP. Thirty-four eyes (59.6%) had extent of RD involving 3 or 4 quadrants. The primary reattachment rate was 93.0%, and the final visual acuity (VA) improved by more than 3 lines in 80.7% of eyes. Neovascular glaucoma occurred in 4 eyes postoperatively. Poor preoperative VA, severe vitreoretinal adhesion, and broad extent of RD had significant correlation with poor visual outcomes. Conclusion. PRP or IVB might play a role in provoking combined RD. The anatomical and functional success rates of surgery were high. Poor preoperative VA and severe proliferations predicted poor visual outcomes. PMID:25061523

  4. 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

  5. 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

  6. Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors

    PubMed Central

    Chen, Chian-Feng; Liou, Shiow-Wen; Wu, Hsin-Han; Lin, Chin-Hui; Huang, Li-Shan; Woung, Lin-Chung; Tsai, Ching-Yao

    2016-01-01

    Objectives: Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR. Methods: At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. Results: We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines. Conclusion: Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.

  7. Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors

    PubMed Central

    Chen, Chian-Feng; Liou, Shiow-Wen; Wu, Hsin-Han; Lin, Chin-Hui; Huang, Li-Shan; Woung, Lin-Chung; Tsai, Ching-Yao

    2016-01-01

    Objectives: Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR. Methods: At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. Results: We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines. Conclusion: Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally. PMID:27648002

  8. 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.

  9. 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.

  10. Non-stereo photographic screening in long-term follow-up for detection of proliferative diabetic retinopathy.

    PubMed

    Kalm, H

    1992-04-01

    The efficiency of two non-stereo photographs of the posterior pole as a screening device in long-term follow-up for the detection of proliferative diabetic retinopathy was evaluated in a clinical setting among 1341 diabetic hospital patients. False positive findings occurred in 0.4% (6/1341). Severe irreversible sight-threatening complications from undetected proliferative diabetic retinopathy, such as retinal traction detachment or secondary glaucoma, never occurred. Vitreous haemorrhages due to missed new vessels in the photographic area occurred in only 2 out of 3020 photographic reading sessions over a 5.5 year period. Evaluation of the nature, localization and magnitude of new vessels showed that optic disc new vessels were generally over-diagnosed in younger patients and missed in patients aged 45 years or older. New vessels elsewhere were more frequently misdiagnosed in patients older than 50 years. New vessels were most commonly found on the temporal arcades (48%) of the eyes and nasal to the optic disc (42%) but were significantly rare beyond the posterior pole (13%) (P less than 0.001). Patients younger than 60 years had significantly more lesions (P less than 0.001) and these lesions tended to be bilateral. Two non-stereo photographs of the posterior pole is a safe and efficient alternative method to conventional survey for proliferative diabetic retinopathy. New vessels are significantly most common in the posterior pole and complications from new vessels occurring exclusively outside the posterior pole can be disregarded. Bilateral neovascularization should be anticipated in patients under 60 years.

  11. 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

  12. Oxidized Low-Density Lipoprotein and the Incidence of Proliferative Diabetic Retinopathy and Clinically Significant Macular Edema Determined From Fundus Photographs

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Lee, Kristine E.; Paterson, Andrew D.; Cruickshanks, Karen J.; Tsai, Michael Y.; Gangnon, Ronald E.; Klein, Barbara E. K.

    2015-01-01

    IMPORTANCE Studies have shown oxidized low-density lipoprotein to be associated with the incidence of proliferative retinopathy and other complications of type 1 diabetes mellitus. Because low-risk interventions are available to modify oxidized low-density lipoprotein, it is important to examine the relationships between this factor and the incidence of proliferative retinopathy and of macular edema, 2 important causes of visual impairment in people with type 1 diabetes. OBJECTIVE To determine the association of oxidized low-density lipoprotein with the worsening of diabetic retinopathy and the incidence of proliferative retinopathy and of macular edema. DESIGN, SETTING, AND PARTICIPANTS Of 996 participants with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy, 730 were examined up to 4 times (1990-1992, 1994-1996, 2005-2007, and 2012-2014) over 24 years and had assays of oxidized low-density lipoprotein and fundus photographs gradable for diabetic retinopathy and macular edema. Analyses started July 2014 and ended February 2015. MAIN OUTCOMES AND MEASURES Worsening of diabetic retinopathy, incidence of proliferative diabetic retinopathy, and incidence of macular edema as assessed via grading of color stereo film fundus photographs. The levels of oxidized low-density lipoprotein collected from serum samples at the time of each examination were measured in 2013 and 2014 from frozen serum. RESULTS The cohort at baseline had a mean (SD) level of oxidized low-density lipoprotein of 30.0 (8.5) U/L. While adjusting for duration of diabetes, glycated hemoglobin A1c level, and other factors, we found that neither the level of oxidized low-density lipoprotein at the beginning of a period nor the change in it over a certain period was associated with the incidence of proliferative diabetic retinopathy (hazard ratio [HR], 1.11 [95% CI, 0.91-1.35], P = .30; odds ratio [OR], 1.77 [95% CI, 0.99-3.17], P = .06), the incidence of macular edema (HR, 1

  13. FOUR-YEAR INCIDENCE AND PROGRESSION OF DIABETIC RETINOPATHY AND MACULAR EDEMA: THE LOS ANGELES LATINO EYE STUDY

    PubMed Central

    Varma, Rohit; Choudhury, Farzana; Klein, Ronald; Chung, Jessica; Torres, Mina; Azen, Stanley P.

    2010-01-01

    Purpose To estimate the 4-year incidence and progression of diabetic retinopathy macular edema (ME), and clinically significant macular edema (CSME) among adult Latinos with diabetes mellitus. Design A population-based, longitudinal study of 4658 self-identified Latinos (primarily Mexican-Americans), residing in Los Angeles, examined at baseline (2000-2003) and at 4 years (2004-2008). Methods Participants underwent a standardized ophthalmic examination. Diabetic retinopathy (DR) and CSME were detected by grading of stereoscopic fundus photographs using the Modified Airlie House classification scheme. Chi-square and trend tests were used to assess differences in incidence when stratifying by age and duration of diabetes. Results The 4-year incidence of DR, ME and CSME was 34.0% (182/535) and 5.4% (38/699) and 7.2% (50/699) respectively. Younger persons and those with longer duration of diabetes mellitus had a higher incidence on DR compared to those who were older and had shorter duration of diabetes mellitus. A higher incidence of ME was associated with longer duration of diabetes mellitus (P=0.004). Worsening/Progression of any DR was found in 38.9% (126/324) and improvement occurred in 14.0% (37/265) of participants. Progression from non-proliferative (NPDR) to proliferative DR (PDR) and from NPDR to PDR with high-risk characteristics occurred in 5.3% and 1.9% of participants. Conclusions The 4-year incidence and progression of DR and the incidence of ME and CSME among Latinos are high compared to non-Hispanic Whites. These findings support the need to identify and modify risk factors associated with these long-term complications. PMID:20149342

  14. Optimal Glycemic and Hemoglobin A1c Thresholds for Diagnosing Diabetes Based on Prevalence of Retinopathy in an Iranian Population

    PubMed Central

    Samadi Aidenloo, Naser; Mehdizadeh, Alireza; Valizadeh, Neda; Abbaszadeh, Mohammad; Qarequran, Siavash; Khalkhali, Hamidreza

    2016-01-01

    Background The use of glycemic thresholds for diabetes diagnosis is controversial. However, no information is available regarding glycemic and glycated hemoglobin (HbA1c) thresholds for detecting diabetic retinopathy (DR) in the Iranian population. Objectives The main purpose of the current investigation was to examine the association of fasting plasma glucose (FPG) and HbA1c levels with diabetic retinopathy (DR), and to determine the relevant cut-off levels in an Iranian population. Patients and Methods This cross-sectional, population-based study was performed during 2012-2013 in Urmia, the capital of West Azerbaijan province, Iran. The subjects were 3,010 Iranians aged 40-81 years. The FPG levels were determined using the glucose oxidase method whereas, the HbA1c values were measured using a standardized assay by high performance liquid chromatography. DR was evaluated by an examination of the fundus photograph of each eye. The photographs were graded according to the international clinical diabetic retinopathy disease severity scale by photograph graders who were masked to the clinical information. Results Of the subjects, 59 had DR. The prevalence of DR increased steeply between the ninth and the tenth deciles for both variables. The ROC curve analysis showed overall glycemic thresholds for DR of 6.5 mmol/L (117 mg/dL) for FPG and 6.2% (44 mmol/mol) for HbA1c. The sensitivities and specificities were 78.0% and 87.1% for FPG and 89.8% and 89.5% for HbA1c, respectively. The areas under the ROC curves indicated that HbA1c was a stronger discriminator of retinopathy: the area under curve was 0.880 for FPG and 0.946 for HbA1c P < 0.001). However, the thresholds for detecting DR for the two measures showed no significant differences after excluding individuals receiving anti-hyperglycemic medication. Conclusions These findings suggest that the HbA1c and FPG thresholds for detecting diabetes in the Iranian population are lower than the current diagnostic criteria

  15. 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

  16. 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

  17. 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.

  18. [Prevalence of diabetic retinopathy and distal symmetrical diabetic polyneuropathy, and glomerular filtration screening upon the diagnosis of type 2 diabetes mellitus - a cohort study].

    PubMed

    Buková, L; Galajda, P; Mokáň, M

    2013-11-01

    The prospective cohort study analyzes the prevalence of microvascular complications at the time of dia-gnosis type 2 diabetes (DM 2). We were monitoring 200 outpatients (117 men and 83 women, aged from 30 to 92 years) with newly diagnosed and previously untreated type 2 diabetes mellitus during the period of August 2007 -  August 2011 accidentally sending GP or internists. Prevalence of diabetic retinopathy in men was 0.85% and in women 1.2%. The prevalence of diabetic distal symetric polyneuropathy in men was 53% and in women 62%. The median of glomerular filtration based on a simplified MDRD 4 equation (according to the study Modification of Diet in Renal Disease) was 1.27 ± 0.6 ml/ s/ 1.73 m2 for men and 1.05 ± 0.32 ml/ s/ 1.73 m2 for women. At baseline, 16.6% of men and 46.2% of women enrolled in our cohort study had glomerular filtration rate < 1 ml/ s/ 1.73 m2. PMID:24279438

  19. 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

  20. Systematic Review and Meta-Analysis of 16 Randomized Clinical Trials of Radix Astragali and Its Prescriptions for Diabetic Retinopathy

    PubMed Central

    Cheng, Lin; Zhang, Gai; Zhou, Yi; Lu, Xuejing; Zhang, Fuwen; Ye, Hejiang; Duan, Junguo

    2013-01-01

    Objective. To evaluate the efficacy and safety of radix astragali and its prescriptions for diabetic retinopathy. Methods. A computer-based online and manual search was conducted for randomized controlled trials addressing radix astragali and its prescriptions for diabetic retinopathy. Results. 16 RCTs involving 977 subjects and 1586 eyes were identified. Meta-analysis indicated that the effect of radix astragali and its prescriptions in improving visual acuity and fundus manifestations, lowering FBG, TG, plasma viscosity, and RAI, was superior to that of control group (WMD or OR 0.20, 0.27, −0.26, −0.36, −0.93, −1.27; 95% CI [0.09, 0.30], [0.17, 0.40], [−0.51, 0.00], [−0.60, −0.12], [−1.67, −0.20], [−2.35, −0.19]; P < 0.05, resp.). In contrary, the efficacy of radix astragali and its prescriptions was not superior to those of control group in descending HbA1C and TC with WMD 0.45, −0.96 and 95% CI [−1.00, 1.90], [−2.19, 0.27], P > 0.05, respectively. GRADE software suggested that the studies were of low methodological quality. Conclusion. Radix astragali and its prescriptions were superior to other treatments for diabetic retinopathy in terms of improving visual acuity and fundus manifestations, reducing FBG, TG, RAI, and plasma viscosity. The evaluated studies were of low methodological quality, indicating that the previous findings should be read with care. PMID:23573153

  1. 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

  2. [Controlled clinical trial of the effect of aspirin and aspirin + dipyridamole on the development of diabetic retinopathy. II. Ophthalmologic protocol].

    PubMed

    1982-12-01

    A description is given of the ophthalmological protocol of the DAMAD (aspirin and dipyridamole + Aspirin) controlled clinical trial in diabetic retinopathy. The 450 patients included in this trial were insulin or noninsulin treated diabetics with an early diabetic retinopathy (i.e. at least five microaneurysms in the posterior pole and/or one zone of capillary non-perfusion). They were randomized in a double blind fashion to treatment with either placebo or aspirin 330 mg or aspirin 330 mg + dipyridamole 75 mg three times daily. A full ophthalmologic examination was performed annually on both eyes of each patient and followed at least three years. Data were recorded on a special form. The main assessment criteria were orientated toward the quantification of the retinal vascular micro-abnormalities, counting of microaneurysm and measurement of the central and peripheral avascular zones. Angiofluorographic photographs were standardized. The two eyes were photographed but only one reference eye was kept for the whole length of this study. A standard reading technique is now used by a technician in charge of coding the quality of the films, the dotting and numbering of the lesions.

  3. 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

  4. 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

  5. Association of macular pigment optical density with early stage of non-proliferative diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

    PubMed Central

    She, Chong-Yang; Gu, Hong; Xu, Jun; Yang, Xiu-Fen; Ren, Xue-Tao; Liu, Ning-Pu

    2016-01-01

    AIM To detect the association between macular pigment optical density (MPOD), which reflects the antioxidant ability of retina, and diabetic retinopathy (DR) and to investigate the correlated factors of MPOD. METHODS Totally 435 subjects of urban Chinese were recruited to the study and divided into 3 groups: non-diabetes mellitus controls (NDM), diabetic patients without retinopathy (DWR), and patients with early stage of non-proliferative diabetic retinopathy (DR). Demographic and lifestyle characteristics were ascertained by questionnaire. A food-frequency questionnaire, general physical and ophthalmic examinations were completed for all participants. MPOD was measured by heterochromatic flicker photometry. Foveal thickness was measured by optical coherence tomography. The difference of MPOD among 3 groups was analyzed by analysis of covariance. The correlation analyses of MPOD with the candidate influence factors were assessed using the generalized estimating equations (GEE) model. RESULTS Of the 435 participants, 34 could not perform the MPOD measurements. Final analysis included 401 subjects, including 48 were in DR group, 134 in DWR group, and 219 in NDM group. MPOD was not significantly different among DR (0.49±0.21), DWR (0.45±0.21), and NDM (0.49±0.17) groups (P=0.24) after adjustment for fasting plasma glycemia, central foveal thickness, green vegetables, Chinese wolfberry, carotene and vitamin E. For all the 401 participants included, MPOD was positively associated with central foveal thickness (E=0.0007, P=0.001), Chinese wolfberry (E=0.0345, P=0.01), and green vegetables (E=0.0596, P<0.001) intake. CONCLUSION The data suggest that MPOD level is not statistically significantly influenced by the onset of diabetes or early stage of DR in the studied population. MPOD level is positively associated with thicker central foveal thickness and higher intake of foods containing carotenoids. PMID:27803860

  6. 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.

  7. Extracellular SOD and VEGF are increased in vitreous bodies from proliferative diabetic retinopathy patients

    PubMed Central

    Izuta, Hiroshi; Chikaraishi, Yuichi; Adachi, Tetsuo; Shimazawa, Masamitsu; Sugiyama, Tetsuya; Ikeda, Tsunehiko

    2009-01-01

    Purpose To evaluate the relationship between vascular endothelial growth factor (VEGF) and extracellular superoxide dismutase (EC-SOD) in vitreous body and serum in patients with proliferative diabetic retinopathy (PDR), and investigate the role of EC-SOD in PDR by evaluating its angiostatic effect, using an in vitro angiogenesis model. To investigate the role of EC-SOD in PDR by evaluating its angiostatic effect, using an in vitro angiogenesis model. Methods EC-SOD and VEGF concentrations in vitreous and serum samples from PDR and macular hole (MH) were measured by ELISA. The effects of EC-SOD on VEGF-induced proliferation, migration, and tube formation were evaluated using human umbilical vein endothelial cells (HUVECs). Moreover, the effects of EC-SOD on VEGF-induced proliferation and migration were evaluated in HUVECs and primary normal human retinal microvascular endothelial cells. Results Intravitreal concentrations of EC-SOD were significantly higher (p<0.01) in PDR (58.0±23.8 ng/ml, mean±SD) than in MH (29.3±6.6 ng/ml). Intravitreal concentrations of VEGF were dramatically higher (p<0.01) in PDR (798.2±882.7 pg/ml) than in MH (17.7±15.5 pg/ml). The serum concentrations of EC-SOD and VEGF did not differ between the two patient groups. The vitreous concentrations of VEGF correlated with those of EC-SOD in all patients (rs=0.61, p<0.001). In HUVECs, EC-SOD at 100 ng/ml significantly suppressed VEGF-induced proliferation and tube formation, but not VEGF-induced migration. Conclusions EC-SOD was increased together with VEGF in the vitreous body from PDR patients, suggesting that EC-SOD may play a pivotal role in the pathogenesis of angiogenesis. PMID:20011081

  8. Relationship between Vitreous Levels of Matrix Metalloproteinases and Vascular Endothelial Growth Factor in Proliferative Diabetic Retinopathy

    PubMed Central

    Abu El-Asrar, Ahmed M.; Mohammad, Ghulam; Nawaz, Mohd. Imtiaz; Siddiquei, Mohammad Mairaj; Van den Eynde, Kathleen; Mousa, Ahmed; De Hertogh, Gert; Opdenakker, Ghislain

    2013-01-01

    To investigate which matrix metalloproteinases (MMPs) are more likely to be involved in the angiogenic process in proliferative diabetic retinopathy (PDR), we measured the levels of MMPs in the vitreous fluid from patients with PDR and controls and correlated these levels with the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 32 PDR and 24 nondiabetic patients were studied by mosaic multiplex MMPs enzyme-linked immunosorbent assay (ELISA), single ELISA, Western blot and zymography analysis. Epiretinal membranes from 11 patients with PDR were studied by immunohistochemistry. MMP-8 and MMP-13 were not detected. ELISA, Western blot and gelatin ymography assays revealed significant increases in the expression levels of MMP-1, MMP-7, MMP-9 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls, whereas MMP-2 and MMP-3 were not upregulated in vitreous samples from PDR patients. Significant correlations existed between ELISA and zymography assays for the quantitation of MMP-2 (r=0.407; p=0.039) and MMP-9 (r=0.711; p<0.001). Significant correlations were observed between levels of VEGF and levels of MMP-1 (r=0.845; P<0.001) and MMP-9 (r=0.775; p<0.001), and between levels of MMP-1 and MMP-9 (r=0.857; p<0.001). In epiretinal membranes, cytoplasmic immunoreactivity for MMP-9 was present in vascular endothelial cells and stromal monocytes/macrophages and neutrophils. Our findings suggest that among the MMPs measured, MMP-1 and MMP-9 may contribute to the angiogenic switch in PDR. PMID:24392031

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Does Insulin Like Growth Factor-1 (IGF-1) Deficiency Have a “Protective” Role in the Development of Diabetic Retinopathy in Thalassamia Major Patients?

    PubMed Central

    De Sanctis, Vincenzo; Incorvaia, Carlo; Soliman, Ashraf T; Candini, Giancarlo; Pepe, Alessia; Kattamis, Christos; Soliman, Nada A.; Elsedfy, Heba; Kholy, Mohamed El

    2015-01-01

    Rationale Both insulin and IGF-1 have been implicated in the control of retinal endothelial cell growth, neovascularization and diabetic retinopathy. Recent findings have established an essential role for IGF-1 in angiogenesis and demonstrated a new target for control of retinopathy that explains why diabetic retinopathy initially increases with the onset of insulin treatment Objective This cross-sectional study was designed to give insights into relationship between Insulin-Growth-Factor 1 (IGF-1) levels and diabetic retinopathy (DR) in a sample of thalassemia major (TM) patients with insulin dependent diabetes mellitus (IDDM). This relation was not previously evaluated, despite the fact that both diseases co-exist in the same patient. The study also describes the clinical and biochemical profile of the associated complications in TM patients with and without IDDM. Design A population-based cross-sectional study. Participants The study includes 19 consecutive TM patients with IDDM and 31 age- and sex-matched TM patients without IDDM who visited our out-patient clinics for an endocrine assessment Methods An extensive medical history, with data on associated complications and current medications, was obtained. Blood samples were drawn in the morning after an overnight fast to measure the serum concentrations of IGF-1, glucose, fructosamine, free thyroxine (FT4), thyrotropin (TSH) and biochemical analysis. Serologic screening assays for hepatitis C virus seropositivity (HCVab and HCV-RNA) were also evaluated; applying routine laboratory methods. Plasma total IGF-1 was measured by a chemiluminescent immunometric assay (CLIA) method. Ophthalmology evaluation was done by the same researcher using stereoscopic fundus biomicroscopy through dilated pupils. DR was graded using the scale developed by the Global Diabetic Retinopathy Group. Iron stores were assessed by direct and indirect methods. Results Eighteen TM patients with IDDM (94.7 %) and ten non-diabetic patients

  15. Imaging and Quantification of Subbasal Nerve Plexus in Healthy Volunteers and Diabetic Patients with or without Retinopathy

    PubMed Central

    Hovakimyan, Marine; Peschel, Sabine; Harder, Volker; Schober, Hans-Christof; Kundt, Guenther; Baltrusch, Simone; Guthoff, Rudolf F.; Stachs, Oliver

    2013-01-01

    Background The alterations of subbasal nerve plexus (SBP) innervation and corneal sensation were estimated non-invasively and compared with the values in healthy volunteers. Additionally, this study addressed the relation of SBP changes to the retinal status, glycemic control and diabetes duration. Methodology/Principal Findings Eighteen eyes of diabetic patients with peripheral diabetic neuropathy aged 68.8±8.8 years and twenty eyes of healthy volunteers aged 66.3±13.3 yrs. were investigated with in vivo confocal laser-scanning microscopy (CLSM). An adapted algorithm for image analysis was used to quantify the morphological and topological properties of SBP. These properties were correlated to incidence of diabetic retinopathy (DR) and corneal sensation (Cochet-Bonnet esthesiometer). The developed algorithm allows a fully automated analysis of pre-segmented SBP structures. Altogether, 10 parameters were analysed, and all of them revealed significant differences between diabetic patients and healthy volunteers. The nerve fibre density, total fibre length and nerve branches were found to be significantly lower in patients with diabetes than those of control subjects (nerve fibre density 0.006±0.002 vs. 0.020±0.007 mm/mm2; total fibre length 6223±2419 vs. 19961±6553 µm; nerve branches 25.3±28.6 vs. 141.9±85.7 in healthy volunteers). Also the corneal sensation was significantly lower in diabetic group when compared to controls (43±11 vs. 59±18 mm). There was found no difference in SBP morphology or corneal sensation in the subgroups with (DR) or without (NDR) diabetic retinopathy. Conclusions/Significance SBP parameters were significantly reduced in diabetic patients, compared to control group. Interestingly, the SBP impairment could be shown even in the diabetic patients without DR. Although automatic adapted image analysis simplifies the evaluation of in vivo CLSM data, image acquisition and quantitative analysis should be optimised for the everyday

  16. The Role of DNA Methylation in the Metabolic Memory Phenomenon Associated With the Continued Progression of Diabetic Retinopathy

    PubMed Central

    Mishra, Manish; Kowluru, Renu A.

    2016-01-01

    Purpose Clinical and experimental studies have shown that diabetic retinopathy progression does not halt after termination of hyperglycemia, suggesting a “metabolic memory” phenomenon. DNA is highly dynamic, and cytosine methylation changes can last for several years. In diabetes, DNA methylation regulates expression of many genes associated with retinal mitochondrial homeostasis. Our aim was to investigate the role of DNA methylation in the metabolic memory. Methods Reversal of 4 days of 20 mM glucose by 4 to 8 days of 5 mM glucose, in the presence/absence of Dnmt inhibitor (5-aza-2′-deoxycytidine), was investigated on DNA methylation and its machinery in human retinal endothelial cells. The key parameters were confirmed in the retina from diabetic rats maintained in good glycemic control (glycated hemoglobin ∼6%) for 3 months after 3 months of poor control (glycated hemoglobin >10%). Results DNA methyltransferase 1 (Dnmt 1) remained active after 4 days of normal glucose that followed 4 days of high glucose, and mtDNA stayed hypermethylated with impaired transcription. Hydroxymethylating enzyme Tet2, and matrix metalloproteinase-9 (regulated by hydroxymethylation) also remained upregulated. But, 8 days of normal glucose after 4 days of high glucose ameliorated mtDNA methylation and MMP-9 hydroxymethylation. Direct Dnmt targeting by Aza during the reversal period benefited methylation status of mtDNA and MMP-9 DNA. Similarly, reinstitution of good control after 3 months of poor control in rats did not reverse diabetes-induced increase in retinal Dnmt1 and Tet2, and alter the methylation status of mtDNA and MMP-9. Conclusions Retinal DNA methylation-hydroxymethylation machinery does not benefit immediately from reversal of hyperglycemia. Maintenance of good glycemic control for longer duration, and/or direct targeting DNA methylation ameliorates continuous mitochondrial damage, and could retard/halt diabetic retinopathy progression. PMID:27787562

  17. 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

  18. 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

  19. 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

  20. 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

  1. Downregulation of serum IGF-1 for treatment of early worsening of diabetic retinopathy: a long-term follow-up of two cases.

    PubMed

    Chantelau, Ernst; Meyer-Schwickerath, Rolf; Klabe, Karsten

    2010-01-01

    In 2003, we reported on 2 cases of nonproliferative and proliferative diabetic retinopathy, subsequent to HbA1c reduction by intensive insulin therapy (so-called early worsening of diabetic retinopathy). This acute condition could partly be reversed by discontinuation of intensive insulin therapy, whereby glycemia increased and serum IGF-1 concentration decreased [Ophthalmologica 2003;217:373-377]. On review 7 years later, both type-2 diabetic patients were on insulin therapy but had failed to achieve good glycemic control. One patient had mild background retinopathy on both eyes, with visual acuity of 1.0 and 0.7 after cataract extraction plus intravitreal triamcinolone injection. The 2nd patient was blind in one eye from secondary glaucoma due to vitrectomy and silicone oil filling; the fellow eye displayed residual retinal neovascularization with a hyaloid membrane and a visual acuity of 0.5. Hence, early worsening as opposed to late worsening of diabetic retinopathy seems to benefit from therapeutic suppression of growth factor action.

  2. 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

  3. The Association of Retinopathy and Plasma Glucose and HbA1c: A Validation of Diabetes Diagnostic Criteria in a Chinese Population

    PubMed Central

    Li, Yufeng; Zhang, Simin

    2016-01-01

    Aims. This study aimed to evaluate the associations of diabetic retinopathy (DR) with fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG), and glycated hemoglobin A1c (HbA1c) in a Chinese population. Materials and Methods. A total of 3124 participants, identified from a population-based survey in Pinggu district, were examined by retinal photography (45°). DR was classified according to the Early Treatment Diabetic Retinopathy Study scale. FPG, 2hPG, and HbA1c were tested and categorized by deciles, with the prevalence of DR calculated in each decile. Results. The prevalence of DR increased sharply in the 10th deciles, when FPG exceeded 7.03 mmol/L and HbA1c exceeded 6.4%. Analysis of the receiver operating characteristic curves showed that the optimal cutoffs for detecting DR were 6.52 mmol/L and 5.9% for FPG and HbA1c, respectively. The World Health Organization (WHO) criteria for diagnosing diabetes showed high specificity (90.5–99.5%) and low sensitivity (35.3–65.0%). Further, 6 individuals with retinopathy had normal plasma glucose; however, their characteristics did not differ from those without retinopathy. Conclusions. Thresholds of FPG and HbA1c for detecting DR were observed, and the WHO criteria of diagnosing diabetes were shown to have high specificity and low sensitivity in this population. PMID:27807545

  4. 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

    Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pesić, Milica; Stanković Babić, Gordana; Milenković, Svetislav; Risimić, Dijana

    2014-08-20

    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.

  5. Polycomb Repressive Complex 2 Regulates MiR-200b in Retinal Endothelial Cells: Potential Relevance in Diabetic Retinopathy

    PubMed Central

    Ruiz, Michael Anthony; Feng, Biao; Chakrabarti, Subrata

    2015-01-01

    Glucose-induced augmented vascular endothelial growth factor (VEGF) production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2), has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation and that inhibition of PRC2 increases miR-200b while reducing VEGF. Furthermore, retinal tissue from animal models of diabetes showed increased expression of major PRC2 components, demonstrating in vivo relevance. This research established a repressive relationship between PRC2 and miR-200b, providing evidence of a novel mechanism of miRNA regulation through histone methylation. PMID:25884496

  6. Automated Quantification of Capillary Nonperfusion Using Optical Coherence Tomography Angiography in Diabetic Retinopathy

    PubMed Central

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

    2016-01-01

    Importance Macular ischemia is a key feature of diabetic retinopathy (DR). Quantification of macular ischemia has potential as a biomarker for DR. Objective To assess the feasibility of automated quantification of capillary nonperfusion as a potential sign of macular ischemia using optical coherence tomography (OCT) angiography. Design, Setting, and Participants An observational study conducted in a tertiary, subspecialty, academic practice evaluated macular nonperfusion with 6 × 6-mm OCT angiography obtained with commercially available 70-kHz OCT and fluorescein angiography (FA). The study was conducted from January 22 to September 18, 2014. Data analysis was performed from October 1, 2014, to April 7, 2015. Participants included 12 individuals with normal vision serving as controls and 12 patients with various levels of DR. Main Outcomes and Measures Preplanned primary measures were parafoveal and perifoveal vessel density, total avascular area, and foveal avascular zone as detected with 6 × 6-mm OCT angiography and analyzed using an automated algorithm. Secondary measures included the agreement of the avascular area between the OCT angiogram and FA. Results Compared with the 12 healthy controls (11 women; mean [SD] age, 54.2 [14.2] years), the 12 participants with DR (4 women; mean [SD] age, 55.1 [12.1] years) had reduced parafoveal and perifoveal vessel density by 12.6% (95% CI, 7.7%-17.5%; P < .001) and 10.4% (95% CI, 6.8%-14.1%; P < .001), respectively. Total avascular area and foveal avascular zone area were greater in eyes with DR by 0.82 mm2 (95% CI. 0.65-0.99 mm2; P = .02) and 0.16 mm2 (95% CI, 0.05-0.28 mm2; P < .001). The agreement between the vascular areas in the OCT angiogram and FA had a κ value of 0.45 (95% CI, 0.21-0.70; P < .001). Total avascular area in the central 5.5-mm-diameter area distinguished eyes with DR from control eyes with 100% sensitivity and specificity. Conclusions and Relevance Avascular area analysis with an automated

  7. 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

  8. 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

  9. 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

  10. Proliferative retinopathies: animal models and therapeutic opportunities.

    PubMed

    Villacampa, Pilar; Haurigot, Virginia; Bosch, Fatima

    2015-01-01

    Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new, more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal proliferative disorders.

  11. [Hypertensive retinopathy--assessment].

    PubMed

    Barar, A; Apatachioaie, Ioana Daniela; Apatachioaie, C; Marceanu, L

    2008-01-01

    The authors intend to make a synthesis of several recent studies available on the Internet regarding hypertensive retinopathy. From the physiopathologic point of view, it is considered that the blood circulation at the level of the retina, choroid and optical nerve has distinct anatomo-physiological properties. It has a different response to the changes in the blood pressure, the result consisting of distinct individual types of the hypertensive disease which can be rendered evident during the optical fundus examination. The retina is considered to be one of the target organs in the hypertensive disease. Ascertaining the retinal changes has advanced from ophthalmoscopy to digital photography studied with appropriate software. The assessment of the hypertensive microangiopathy is subjected to a wide intra- and interobserver variability an accurate assessment requiring specialized software and standardized protocols. There is also a lack of consensus regarding the classification of hypertensive retinopathy and the usefulness of retinal examination in the assessment of cardiovascular risk. The Keith and Scheie staging scales are still in use, but they do not allow the clinician to differentiate slight or even moderate changes at the level of the retina of hypertensive patients. Furthermore, they do not correlate enough with the severity of the high blood pressure and they are not supported by the angiofluorography studies. There are not enough motives for the recommendation of a routine ophthalmoscopic examination for all hypertensive patients. It is required for patients with stage-3 hypertension. It is also recommended when the initial clinical signs are equivocal, as in borderline or fluctuating high blood pressure without any other obvious signs from the target organs, for diabetic patients, or in the presence of visual symptoms. The clinical implications of hypertensive retinopathy being unclear, many of the authors do not recommend ophthalmoscopic examination as

  12. Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy

    PubMed Central

    Berkowitz, Bruce A.; Grady, Edmund Michael; Khetarpal, Nikita; Patel, Akshar; Roberts, Robin

    2015-01-01

    Purpose. To test the hypothesis that in a mouse model of diabetic retinopathy, oxidative stress is linked with impaired light-evoked expansion of choroidal thickness and subretinal space (SRS). Methods. We examined nondiabetic mice (wild-type, wt) with and without administration of manganese, nondiabetic mice deficient in rod phototransduction (transducin alpha knockout; GNAT1−/−), and diabetic mice (untreated or treated with the antioxidant α-lipoic acid [LPA]). Magnetic resonance imaging (MRI) was used to measure light-evoked increases in choroidal thickness and the apparent diffusion coefficient (ADC) at 88% to 100% depth into the retina (i.e., the SRS layer). Results. Choroidal thickness values were similar (P > 0.05) between all untreated nondiabetic dark-adapted groups and increased significantly (P < 0.05) with light; this expansion was subnormal (P < 0.05) in both diabetic groups. Apparent diffusion coefficient values in the SRS layer robustly increased (P < 0.05) in a light duration-dependent manner, and this effect was independent of the presence of Mn2+. The light-stimulated increase in ADC at the location of the SRS was absent in GNAT1−/− and diabetic mice (P > 0.05). In diabetic mice, the light-dependent increase in SRS ADC was significantly (P < 0.05) restored with LPA. Conclusions. Apparent diffusion coefficient MRI is a sensitive method for evaluating choroid thickness and its light-evoked expansion together with phototransduction-dependent changes in the SRS layer in mice in vivo. Because ADC MRI exploits an endogenous contrast mechanism, its translational potential is promising; it can also be performed in concert with manganese-enhanced MRI (MEMRI). Our data support a link between diabetes-related oxidative stress and rod, but not choroidal, pathophysiology. PMID:25574049

  13. Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia.

    PubMed

    Satyanarayana, Alleboena; Balakrishna, Nagalla; Pitla, Sujatha; Reddy, Paduru Yadagiri; Mudili, Sivaprasad; Lopamudra, Pratti; Suryanarayana, Palla; Viswanath, Kalluru; Ayyagari, Radha; Reddy, Geereddy Bhanuprakash

    2011-01-01

    Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case-control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.

  14. Assessment of Diabetic Retinopathy Using Nonmydriatic Ultra-Widefield Scanning Laser Ophthalmoscopy (Optomap) Compared With ETDRS 7-Field Stereo Photography

    PubMed Central

    Kernt, Marcus; Hadi, Indrawati; Pinter, Florian; Seidensticker, Florian; Hirneiss, Christoph; Haritoglou, Christos; Kampik, Anselm; Ulbig, Michael W.; Neubauer, Aljoscha S.

    2012-01-01

    OBJECTIVE To compare the diagnostic properties of a nonmydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) versus mydriatic Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field photography for diabetic retinopathy (DR) screening. RESEARCH DESIGN AND METHODS A consecutive series of 212 eyes of 141 patients with different levels of DR were examined. Grading of DR and clinically significant macular edema (CSME) from mydriatic ETDRS 7-field stereo photography was compared with grading obtained by Optomap Panoramic 200 SLO images. All SLO scans were performed through an undilated pupil, and no additional clinical information was used for evaluation of all images by the two independent, masked, expert graders. RESULTS Twenty-two eyes from ETDRS 7-field photography and 12 eyes from Optomap were not gradable by at least one grader because of poor image quality. A total of 144 eyes were analyzed regarding DR level and 155 eyes regarding CSME. For ETDRS 7-field photography, 22 eyes (18 for grader 2) had no or mild DR (ETDRS levels ≤ 20) and 117 eyes (111 for grader 2) had no CSME. A highly substantial agreement between both Optomap DR and CSME grading and ETDRS 7-field photography existed with κ = 0.79 for DR and 0.73 for CSME for grader 1, and κ = 0.77 (DR) and 0.77 (CSME) for grader 2. CONCLUSIONS Determination of CSME and grading of DR level from Optomap Panoramic 200 nonmydriatic images show a positive correlation with mydriatic ETDRS 7-field stereo photography. Both techniques are of sufficient quality to assess DR and CSME. Optomap Panoramic 200 images cover a larger retinal area and therefore may offer additional diagnostic properties. PMID:22912430

  15. Interaction between peroxisome proliferator- activated receptor gamma polymorphism and overweight on diabetic retinopathy in a Chinese case-control study

    PubMed Central

    Wang, Yan; Wang, Xin-Hua; Li, Ruo-Xi

    2015-01-01

    Background: Peroxisome proliferator-activated receptors γ (PPAR γ) and overweight were both associated with diabetic retinopathy (DR), so the aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) of PPAR γ with DR and additional role of gene-BMI interaction. Methods: A total of 500 patients with T2DM (236 men, 264 women), with a mean age of 54.3 ± 15.8 years old, were selected, including 247 diabetic retinopathy patients and 253 controls. Four SNPs were selected for genotyping in the case-control study: rs1805192, rs709158, rs3856806, rs4684847. Logistic regression model was used to examine the interaction between SNP and overweight on DR, odds ratio (OR) and 95% confident interval (95% CI) were calculated. Results: The carriers of C allele of the rs1805192 polymorphism revealed decreased DR risk than those with Pro/Pro variants (Pro/Ala+Ala/Ala versus Pro/Pro, adjusted OR (95% CI)=0.86 (0.65-0.96), P=0.012), after adjusting for covariates. We also found that obese subjects with Pro/Ala or Ala/Ala variants genotype have lowest DR risk, compared to obese subjects with Pro/Pro genotype or non- obese subjects with Pro/Ala or Ala/Ala (OR=0.40, 95% CI=0.32-0.63), after covariates adjustment. Conclusions: Our results support an important association between rs1805192 minor allele (Ala allele) of PPAR γ and DR, the interaction analysis shown a combined effect of Ala- BMI interaction on DR. PMID:26885119

  16. Subfoveal Choroidal Thickness after Panretinal Photocoagulation with Red and Green Laser in Bilateral Proliferative Diabetic Retinopathy Patients: Short Term Results

    PubMed Central

    Roohipoor, Ramak; Dantism, Sina; Karkhaneh, Reza; Zarei, Mohammad; Ghasemi, Fariba

    2016-01-01

    Purpose. To compare subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness after panretinal photocoagulation (PRP) with red and green laser in diabetic patients. Study Design. Randomized clinical trial. Methods. A total of 50 patients with bilateral proliferative diabetic retinopathy and no diabetic macular edema underwent PRP. One eye was randomly assigned to red or green laser. Subfoveal choroidal, central retinal, and RNFL thicknesses were evaluated at baseline and 6 weeks after treatment. Results. The mean subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness increased significantly in each eye 6 weeks after PRP (P values in red laser group: <0.01, 0.03, and <0.01, resp., and in green laser group <0.01, <0.01, and <0.01). There was no difference between red and green laser considering subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness increase after PRP (P values: 0.184, 0.404, and 0.726, resp.). Conclusion. Both red and green lasers increased mean subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness significantly 6 weeks after PRP, but there is no difference between these two modalities in this regard. PMID:27595017

  17. Subfoveal Choroidal Thickness after Panretinal Photocoagulation with Red and Green Laser in Bilateral Proliferative Diabetic Retinopathy Patients: Short Term Results.

    PubMed

    Roohipoor, Ramak; Dantism, Sina; Ahmadraji, Aliasghar; Karkhaneh, Reza; Zarei, Mohammad; Ghasemi, Fariba

    2016-01-01

    Purpose. To compare subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness after panretinal photocoagulation (PRP) with red and green laser in diabetic patients. Study Design. Randomized clinical trial. Methods. A total of 50 patients with bilateral proliferative diabetic retinopathy and no diabetic macular edema underwent PRP. One eye was randomly assigned to red or green laser. Subfoveal choroidal, central retinal, and RNFL thicknesses were evaluated at baseline and 6 weeks after treatment. Results. The mean subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness increased significantly in each eye 6 weeks after PRP (P values in red laser group: <0.01, 0.03, and <0.01, resp., and in green laser group <0.01, <0.01, and <0.01). There was no difference between red and green laser considering subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness increase after PRP (P values: 0.184, 0.404, and 0.726, resp.). Conclusion. Both red and green lasers increased mean subfoveal choroidal, central retinal, and peripapillary nerve fiber layer (RNFL) thickness significantly 6 weeks after PRP, but there is no difference between these two modalities in this regard. PMID:27595017

  18. Combined renin inhibition/(pro)renin receptor blockade in diabetic retinopathy--a study in transgenic (mREN2)27 rats.

    PubMed

    Batenburg, Wendy W; Verma, Amrisha; Wang, Yunyang; Zhu, Ping; van den Heuvel, Mieke; van Veghel, Richard; Danser, A H Jan; Li, Qiuhong

    2014-01-01

    Dysfunction of renin-angiotensin system (RAS) contributes to the pathogenesis of diabetic retinopathy (DR). Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (pro)renin receptor ((P)RR). Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (P)RR blocker handle-region peptide (HRP) on diabetic retinopathy in streptozotocin (STZ)-induced diabetic transgenic (mRen2)27 rats (a model with high plasma prorenin levels) as well as prorenin stimulated cytokine expression in cultured Müller cells. Adult (mRen2)27 rats were randomly divided into the following groups: (1) non-diabetic; (2) diabetic treated with vehicle; (3) diabetic treated with aliskiren (10 mg/kg per day); and (4) diabetic treated with aliskiren+HRP (1 mg/kg per day). Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen2)27 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen2)27 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Müller cells, prorenin significantly increased the expression levels of IL-1α and TNF-α, and this was completely blocked by aliskiren or HRP, their combination, (P)RR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (P)RR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular

  19. Posttranslational modification of mitochondrial transcription factor A in impaired mitochondria biogenesis: implications in diabetic retinopathy and metabolic memory phenomenon.

    PubMed

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

    2014-04-01

    Mitochondrial transcription factor A (TFAM) is one of the key regulators of the transcription of mtDNA. In diabetes, despite increase in gene transcripts of TFAM, its protein levels in the mitochondria are decreased and mitochondria copy numbers become subnormal. The aim of this study is to investigate the mechanism(s) responsible for decreased mitochondrial TFAM in diabetes. Using retinal endothelial cells, we have investigated the effect of overexpression of cytosolic chaperone, Hsp70, and TFAM on glucose-induced decrease in mitochondrial TFAM levels, and the transcription of mtDNA-encoded genes, NADH dehydrogenase subunit 6 (ND6) and cytochrome b (Cytb). To investigate the role of posttranslational modifications in subnormal mitochondrial TFAM, ubiquitination of TFAM was assessed, and the results were confirmed in the retina from streptozotocin-induced diabetic rats. While overexpression of Hsp70 failed to prevent glucose-induced decrease in mitochondrial TFAM and transcripts of ND6 and Cytb, overexpression of TFAM ameliorated decrease in its mitochondrial protein levels and transcriptional activity. TFAM was ubiquitinated by high glucose, and PYR-41, an inhibitor of ubiquitination, prevented TFAM ubiquitination and restored the transcriptional activity. Similarly, TFAM was ubiquitinated in the retina from diabetic rats, and it continued to be modified after reinstitution of normal glycemia. Our results clearly imply that the ubiquitination of TFAM impedes its transport to the mitochondria resulting in subnormal mtDNA transcription and mitochondria dysfunction, and inhibition of ubiquitination restores mitochondrial homeostasis. Reversal of hyperglycemia does not provide any benefit to TFAM ubiquitination. Thus, strategies targeting posttranslational modification could provide an avenue to preserve mitochondrial homeostasis, and inhibit the development/progression of diabetic retinopathy.

  20. Effects of nuclear factor κB expression on retinal neovascularization and apoptosis in a diabetic retinopathy rat model

    PubMed Central

    Jiang, Ning; Chen, Xiao-Long; Yang, Hong-Wei; Ma, Yu-Ru

    2015-01-01

    AIM To investigate the expression and role of nuclear factor κB (NF-κB) in diabetic retinopathy (DR) and its relationship with neovascularization and retinal cell apoptosis. METHODS A total of 80 male Wistar rats were randomly assigned to control (4, 8, 12 and 16wk, n=10 in each group) and diabetes mellitus (DM) groups (4, 8, 12 and 16wk, n=10 in each group). A diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg). After 4, 8, 12 and 16wk, rats were sacrificed. Retinal layers and retinal neovascularization growth were stained with hematoxylin-eosin and examined under light microscopy. Cell apoptosis in the retina was detected by TdT-mediated dUTP nick end labeling, and NF-κB distribution and expression in the retina was determined using immunohistochemistry. RESULTS DM model success rate up to 100%. Diabetes model at each time point after the experimental groupcompared with the control group, the blood glucose was significantly increased, decreased body weight, each time point showed significant differences compared with the control group (P<0.01). After 12wk other pathological changes in the retina of diabetic rats were observed; after 16wk, neovascularization were observed. After 1mo, retinal cell apoptosis was observed. Compared with the control group, NF-κB expression in the DM group significantly increased with disease duration. CONCLUSION With the prolonging of DM progression, the expression NF-κB increases. NF-κB may be related to retinal cell apoptosis and neovascularization. PMID:26085989

  1. Posttranslational Modification of Mitochondrial Transcription Factor A in Impaired Mitochondria Biogenesis: Implications in Diabetic Retinopathy and Metabolic Memory Phenomenon

    PubMed Central

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

    2014-01-01

    Mitochondrial transcription factor A (TFAM) is one of the key regulators of the transcription of mtDNA. In diabetes, despite increase in gene transcripts of TFAM, its protein levels in the mitochondria are decreased and mitochondria copy numbers become subnormal. The aim of this study is to investigate the mechanism(s) responsible for decreased mitochondrial TFAM in diabetes. Using retinal endothelial cells, we have investigated the effect of overexpression of cytosolic chaperone, Hsp70, and TFAM on glucose-induced decrease in mitochondrial TFAM levels, and the transcription of mtDNA-encoded genes, NADH dehydrogenase subunit 6 (ND6) and cytochrome b (Cytb). To investigate the role of posttranslational modifications in subnormal mitochondrial TFAM, ubiquitination of TFAM was accessed, and the results were confirmed in the retina from streptozotocin-induced diabetic rats. While overexpression of Hsp70 failed to prevent glucose-induced decrease in mitochondrial TFAM and transcripts of ND6 and Cytb, overexpression of TFAM ameliorated decrease in its mitochondrial protein levels and transcriptional activity. TFAM was ubiquitinated by high glucose, and PYR-41, an inhibitor of ubiquitination, prevented TFAM ubiquitination and restored the transcriptional activity. Similarly, TFAM was ubiquitinated in the retina from diabetic rats, and it continued to be modified after reinstitution of normal glycemia. Our results clearly imply that the ubiquitination of TFAM impedes its transport to the mitochondria resulting in subnormal mtDNA transcription and mitochondria dysfunction, and inhibition of ubiquitination restores mitochondrial homeostasis. Reversal of hyperglycemia does not provide any benefit to TFAM ubiquitination. Thus, strategies targeting posttranslational modification could provide an avenue to preserve mitochondrial homeostasis, and inhibit the development/progression of diabetic retinopathy. PMID:24607487

  2. Association study of sorbitol dehydrogenase -888G>C polymorphism with type 2 diabetic retinopathy in Caucasian-Brazilians.

    PubMed

    Ferreira, Fábio Netto; Crispim, Daisy; Canani, Luís Henrique; Gross, Jorge Luiz; dos Santos, Kátia Gonçalves

    2013-10-01

    Diabetic retinopathy (DR) is a common chronic complication of diabetes and remains the leading cause of blindness in working-aged people. Hyperglycemia increases glucose flux through the polyol pathway, in which aldose reductase converts glucose into intracellular sorbitol, which is subsequently converted to fructose by sorbitol dehydrogenase (SDH). The accelerated polyol pathway triggers a cascade of events leading to retinal vascular endothelial dysfunction and the eventual development of DR. Polymorphisms in the gene encoding aldose reductase have been consistently associated with DR. However, only two studies have analyzed the relationship between polymorphisms in the gene encoding SDH (SORD) and DR. In this case-control study, we investigated whether the -888G > C polymorphism (rs3759890) in the SORD gene is associated with the presence or severity of DR in 446 Caucasian-Brazilians with type 2 diabetes (241 subjects with and 205 subjects without DR). The -888G > C polymorphism was also examined in 105 healthy Caucasian blood donors, and the genotyping of this polymorphism was carried out by real-time PCR. The genotype and allele frequencies of the -888G > C polymorphism in patients with type 2 diabetes were similar to those of blood donors (G allele frequency = 0.16 in both groups of subjects). Similarly, the genotype and allele frequencies in patients with DR or the proliferative form of DR were similar to those of patients without this complication (P > 0.05 for all comparisons). Thus, our findings suggest that the -888G > C polymorphism in the SORD gene is not involved in the pathogenesis of DR in type 2 diabetes.

  3. The Evolution of Teleophthalmology Programs in the United Kingdom: Beyond Diabetic Retinopathy Screening.

    PubMed

    Sim, Dawn A; Mitry, Danny; Alexander, Philip; Mapani, Adam; Goverdhan, Srini; Aslam, Tariq; Tufail, Adnan; Egan, Catherine A; Keane, Pearse A

    2016-03-01

    Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system. Concurrently, there have been exponential increases in computing power, expansions in the strength and ubiquity of communications technologies, and developments in imaging capabilities. Advances in imaging have been not only in terms of resolution, but also in terms of anatomical coverage, allowing new inferences to be made. In spite of this, image analysis techniques are still currently superseded by expert ophthalmologist interpretation. Teleophthalmology is therefore currently perfectly placed to face this urgent and immediate challenge of provision of optimal and expert care to remote and multiple patients over widespread geographical areas. This article reviews teleophthalmology programs currently deployed in the United Kingdom, focusing on diabetic eye care but also discussing glaucoma, emergency eye care, and other retinal diseases. We examined current programs and levels of evidence for their utility, and explored the relationships between screening, teleophthalmology, disease detection, and monitoring before discussing aspects of health economics pertinent to diabetic eye care. The use of teleophthalmology presents an immense opportunity to manage the steadily increasing demand for eye care, but challenges remain in the delivery of practical, viable, and clinically proven solutions.

  4. Searching in the Dark: Phenotyping Diabetic Retinopathy in a De-Identified Electronic Medical Record Sample of African Americans.

    PubMed

    Restrepo, Nicole A; Farber-Eger, Eric; Crawford, Dana C

    2016-01-01

    A hurdle to EMR-based studies is the characterization and extraction of complex phenotypes not readily defined by single diagnostic/procedural codes. Here we developed an algorithm utilizing data mining techniques to identify a diabetic retinopathy (DR) cohort of type-2 diabetic African Americans from the Vanderbilt University de-identified EMR system. The algorithm incorporates a combination of diagnostic codes, current procedural terminology billing codes, medications, and text matching to identify DR when gold-standard digital photography results were unavailable. DR cases were identified with a positive predictive value of 75.3% and an accuracy of 84.8%. Controls were classified with a negative predictive value of 1.0% as could be assessed. Limited studies of DR have been performed in African Americans who are at an elevated risk of DR. Identification of EMR-based African American cohorts may help stimulate new biomedical studies that could elucidate differences in risk for the development of DR and other complex diseases.

  5. Searching in the Dark: Phenotyping Diabetic Retinopathy in a De-Identified Electronic Medical Record Sample of African Americans.

    PubMed

    Restrepo, Nicole A; Farber-Eger, Eric; Crawford, Dana C

    2016-01-01

    A hurdle to EMR-based studies is the characterization and extraction of complex phenotypes not readily defined by single diagnostic/procedural codes. Here we developed an algorithm utilizing data mining techniques to identify a diabetic retinopathy (DR) cohort of type-2 diabetic African Americans from the Vanderbilt University de-identified EMR system. The algorithm incorporates a combination of diagnostic codes, current procedural terminology billing codes, medications, and text matching to identify DR when gold-standard digital photography results were unavailable. DR cases were identified with a positive predictive value of 75.3% and an accuracy of 84.8%. Controls were classified with a negative predictive value of 1.0% as could be assessed. Limited studies of DR have been performed in African Americans who are at an elevated risk of DR. Identification of EMR-based African American cohorts may help stimulate new biomedical studies that could elucidate differences in risk for the development of DR and other complex diseases. PMID:27570675

  6. Searching in the Dark: Phenotyping Diabetic Retinopathy in a De-Identified Electronic Medical Record Sample of African Americans

    PubMed Central

    Restrepo, Nicole A.; Farber-Eger, Eric; Crawford, Dana C.

    2016-01-01

    A hurdle to EMR-based studies is the characterization and extraction of complex phenotypes not readily defined by single diagnostic/procedural codes. Here we developed an algorithm utilizing data mining techniques to identify a diabetic retinopathy (DR) cohort of type-2 diabetic African Americans from the Vanderbilt University de-identified EMR system. The algorithm incorporates a combination of diagnostic codes, current procedural terminology billing codes, medications, and text matching to identify DR when gold-standard digital photography results were unavailable. DR cases were identified with a positive predictive value of 75.3% and an accuracy of 84.8%. Controls were classified with a negative predictive value of 1.0% as could be assessed. Limited studies of DR have been performed in African Americans who are at an elevated risk of DR. Identification of EMR-based African American cohorts may help stimulate new biomedical studies that could elucidate differences in risk for the development of DR and other complex diseases. PMID:27570675

  7. Effect of Hemodialysis on Retinal Thickness in Patients with Diabetic Retinopathy, with and without Macular Edema, Using Optical Coherence Tomography

    PubMed Central

    Azem, Nur; Spierer, Oriel; Shaked, Meital; Neudorfer, Meira

    2014-01-01

    Background. Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear. Objective. To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD. Methods. Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD. Results. We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value—Kt/V, glycemic hemoglobin, or albumin levels before and after HD. Conclusions. HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study. PMID:25298889

  8. Effect of Hemodialysis on Retinal Thickness in Patients with Diabetic Retinopathy, with and without Macular Edema, Using Optical Coherence Tomography.

    PubMed

    Azem, Nur; Spierer, Oriel; Shaked, Meital; Neudorfer, Meira

    2014-01-01

    Background. Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear. Objective. To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD. Methods. Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD. Results. We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value-Kt/V, glycemic hemoglobin, or albumin levels before and after HD. Conclusions. HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study. PMID:25298889

  9. Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients.

    PubMed

    Errera, F I V; Silva, M E R; Yeh, E; Maranduba, C M C; Folco, B; Takahashi, W; Pereira, A C; Krieger, J E; Passos-Bueno, M R

    2006-07-01

    Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and epsilon2/epsilon3/epsilon4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (epsilon2, epsilon3 and epsilon4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of epsilon2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/107 (6.5%); P < 0.05]. Therefore, our results suggest that the epsilon2 allele/APOE might be a risk factor for diabetes in the Brazilian population.

  10. RECENT ADVANCES IN CHILDHOOD DIABETES MELLITUS

    PubMed Central

    Ayoola, O.O.

    2008-01-01

    Diabetes mellitus (DM) is a syndrome characterized by disturbed metabolism of carbohydrate, protein, and fat. It is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin. It presents with very different medical and psychosocial issues in children. Epidemiological studies indicate that there is gradual but steady increase in the incidence of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in both developed and developing countries. The manifestations, therapy goals, clinical course, susceptibility to complications of diabetes differ among childhood cases. T1DM accounts for the majority of cases of diabetes in children. Diabetic ketoacidosis may be the initial presentation of T1DM in many children particularly in Africa probably due to low level of awareness. The focus of this review on T1DM is to provide an overview of the major advances in the aetiology, pathogenesis, and clinical management of newly diagnosed children and their subsequent management with the aim of ensuring optimal growth and development as well as preventing acute and chronic complications. The advances in insulin therapy and regimens and the presentation and management of diabetic ketoacidosis are discussed. The prospects for the cure of the disease are also highlighted in this review. PMID:25161448

  11. The Degree of Diabetic Retinopathy in Patients with Type 2 Diabetes Correlates with the Presence and Severity of Coronary Heart Disease

    PubMed Central

    2016-01-01

    Both diabetic retinopathy (DR) and coronary heart disease (CHD) are clinically significant in diabetic patients. We investigated the correlation between the severity of DR and the presence and severity of CHD among type 2 diabetic patients. A total of 175 patients who were examined at the DR clinic and underwent dual-source computed tomography (DSCT) angiography within 6 months were included. The degree of DR was graded as no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). The severity of CHD and the numbers of significant stenotic coronary artery on DSCT angiography according to DR grade were assessed. The mean Agatston Calcium Score (ACS) in patients with PDR was significantly higher than other groups (P < 0.001). The overall odds of an ACS increase were about 4.7-fold higher in PDR group than in no DR group (P < 0.001). In PDR group, in comparison with in no DR, the odds of having 1 or 2 arterial involvement were 3-fold higher (P = 0.044), and those of having 3 were 17-fold higher (P = 0.011). The c-index, one of the predictability values in regression analysis model, was not significantly increased when PDR was added to classical CHD risk factors (0.671 to 0.706, P = 0.111). Conclusively, patients with PDR develop a greater likelihood of not only having CHD, but being more severe nature. PDR has no additional effect to classical CHD risk factors for predicting CHD. PMID:27478342

  12. Imbalance of the nerve growth factor and its precursor as a potential biomarker for diabetic retinopathy.

    PubMed

    Mysona, B A; Matragoon, S; Stephens, M; Mohamed, I N; Farooq, A; Bartasis, M L; Fouda, A Y; Shanab, A Y; Espinosa-Heidmann, D G; El-Remessy, A B

    2015-01-01

    Our previous studies have demonstrated that diabetes-induced oxidative stress alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation of its precursor, proNGF, at the expense of NGF which plays a critical role in preserving neuronal and retinal function. This imbalance coincided with retinal damage in experimental diabetes. Here we test the hypothesis that alteration of proNGF and NGF levels observed in retina and vitreous will be mirrored in serum of diabetic patients. Blood and vitreous samples were collected from patients (diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University under approved IRB. Levels of proNGF, NGF, and p75(NTR) shedding were detected using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced proNGF expression and impaired NGF expression were observed in vitreous and serum. Vitreous and sera from diabetic patients (n = 11) showed significant 40.8-fold and 3.6-fold increases, respectively, compared to nondiabetics (n = 9). In contrast, vitreous and sera from diabetic patients showed significant 44% and 64% reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF ratios showed significant correlation between vitreous and serum. Further characterization of diabetes-induced imbalance in the proNGF to NGF ratio will facilitate its utility as an early biomarker for diabetic complications. PMID:25853140

  13. Diabetic retinopathy screening with pharmacy-based teleophthalmology in a semiurban setting: a cost-effectiveness analysis

    PubMed Central

    Coronado, Andrea C.; Zaric, Gregory S.; Martin, Janet; Malvankar-Mehta, Monali; Si, Francie F.; Hodge, William G.

    2016-01-01

    Background: Diabetic eye complications are the leading cause of visual loss among working-aged people. Pharmacy-based teleophthalmology has emerged as a possible alternative to in-person examination that may facilitate compliance with evidence-based recommendations and reduce barriers to specialized eye care. The objective of this study was to estimate the cost-effectiveness of mobile teleophthalmology screening compared with in-person examination (primary care) for the diabetic population residing in semiurban areas of southwestern Ontario. Methods: A decision tree was constructed to compare in-person examination (comparator program) versus pharmacy-based teleophthalmology (intervention program). The economic model was designed to identify patients with more than minimal diabetic retinopathy, manifested by at least 1 microaneurysm at examination (modified Airlie House classification grade of ≥ 20). Cost-effectiveness was assessed as cost per case detected (true-positive result) and cost per case correctly diagnosed (including true-positive and true-negative results). Results: The cost per case detected was $510 with in-person examination and $478 with teleophthalmology, and the cost per case correctly diagnosed was $107 and $102 respectively. The incremental cost-effectiveness ratio was $314 per additional case detected and $73 per additional case correctly diagnosed. Use of pharmacologic dilation and health care specialists' fees were the most important cost drivers. Interpretation: The study showed that a compound teleophthalmology program in a semiurban community would be more effective but more costly than in-person examination. The findings raise the question of whether the benefits of pharmacy-based teleophthalmology in semiurban areas, where in-person examination is still available, are equivalent to those observed in remote communities. Further study is needed to investigate the impact of this program on the prevention of severe vision loss and quality

  14. Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model.

    PubMed

    Wu, Jiangchun; Wang, Ruobing; Ye, Zhouheng; Sun, Xuejun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

    2015-10-16

    As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs.

  15. Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model.

    PubMed

    Wu, Jiangchun; Wang, Ruobing; Ye, Zhouheng; Sun, Xuejun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

    2015-10-16

    As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs. PMID:26363454

  16. Surgery for Diabetic Eye Complications.

    PubMed

    Berrocal, María H; Acaba, Luis A; Acaba, Alexandra

    2016-10-01

    New modalities for the treatment of diabetic eye complications have emerged in the past decade. Nevertheless, many severe diabetic retinopathy complications can only be treated with vitreoretinal surgery. Technological advances in pars plana vitrectomy have expanded the gamut of pathologies that can be successfully treated with surgery. The most common pathologies managed surgically include vitreous opacities and traction retinal detachment. The indications, surgical objectives, adjunctive pharmacotherapy, microincisional surgical techniques, and outcomes of diabetic vitrectomy for proliferative diabetic retinopathy and diabetic tractional retinal detachment will be discussed. With the availability of new microincisional vitrectomy technology, wide angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from proliferative diabetic retinopathy.

  17. Surgery for Diabetic Eye Complications.

    PubMed

    Berrocal, María H; Acaba, Luis A; Acaba, Alexandra

    2016-10-01

    New modalities for the treatment of diabetic eye complications have emerged in the past decade. Nevertheless, many severe diabetic retinopathy complications can only be treated with vitreoretinal surgery. Technological advances in pars plana vitrectomy have expanded the gamut of pathologies that can be successfully treated with surgery. The most common pathologies managed surgically include vitreous opacities and traction retinal detachment. The indications, surgical objectives, adjunctive pharmacotherapy, microincisional surgical techniques, and outcomes of diabetic vitrectomy for proliferative diabetic retinopathy and diabetic tractional retinal detachment will be discussed. With the availability of new microincisional vitrectomy technology, wide angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from proliferative diabetic retinopathy. PMID:27612846

  18. Nonmydriatic ultra-wide-field scanning laser ophthalmoscopy (Optomap) versus two-field fundus photography in diabetic retinopathy.

    PubMed

    Liegl, Raffael; Liegl, Kristine; Ceklic, Lala; Haritoglou, Christos; Kampik, Anselm; Ulbig, Michael W; Kernt, Marcus; Neubauer, Aljoscha S

    2014-01-01

    The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.

  19. An automated decision-support system for non-proliferative diabetic retinopathy disease based on MAs and HAs detection.

    PubMed

    Saleh, Marwan D; Eswaran, C

    2012-10-01

    Diabetic retinopathy (DR) has become a serious threat in our society, which causes 45% of the legal blindness in diabetes patients. Early detection as well as the periodic screening of DR helps in reducing the progress of this disease and in preventing the subsequent loss of visual capability. This paper provides an automated diagnosis system for DR integrated with a user-friendly interface. The grading of the severity level of DR is based on detecting and analyzing the early clinical signs associated with the disease, such as microaneurysms (MAs) and hemorrhages (HAs). The system extracts some retinal features, such as optic disc, fovea, and retinal tissue for easier segmentation of dark spot lesions in the fundus images. That is followed by the classification of the correctly segmented spots into MAs and HAs. Based on the number and location of MAs and HAs, the system quantifies the severity level of DR. A database of 98 color images is used in order to evaluate the performance of the developed system. From the experimental results, it is found that the proposed system achieves 84.31% and 87.53% values in terms of sensitivity for the detection of MAs and HAs respectively. In terms of specificity, the system achieves 93.63% and 95.08% values for the detection of MAs and HAs respectively. Also, the proposed system achieves 68.98% and 74.91% values in terms of kappa coefficient for the detection of MAs and HAs respectively. Moreover, the system yields sensitivity and specificity values of 89.47% and 95.65% for the classification of DR versus normal.

  20. Periostin, discovered by nano-flow liquid chromatography and mass spectrometry, is a novel marker of diabetic retinopathy

    SciTech Connect

    Takada, Michiya; Ban, Yoshiyuki; Yamamoto, Gou; Ueda, Toshihiko; Saito, Yuta; Nishimura, Eiichi; Fujisawa, Kunimi; Koide, Ryohei; Mizutani, Masakazu; Kozawa, Tadahiko; Shiraishi, Yuji; Bando, Yasuhiko; Tachikawa, Tetsuhiko; Hirano, Tsutomu

    2010-08-20

    Research highlights: {yields} In proliferative membrane and epiretinal membrane specimens, the numbers of proteins are 225 and 154, respectively, and 123 proteins are common to both. {yields} Periostin and thrombospondin-1 proteins are unique to the proliferative membrane specimens. {yields} The expression of periostin is significantly up-regulated in proliferative membrane specimens. -- Abstract: Diabetes can lead to serious microvascular complications including proliferative diabetic retinopathy (PDR), the leading cause of blindness in adults. Recent studies using gene array technology have attempted to apply a hypothesis-generating approach to elucidate the pathogenesis of PDR, but these studies rely on mRNA differences, which may or may not be related to significant biological processes. To better understand the basic mechanisms of PDR and to identify potential new biomarkers, we performed shotgun liquid chromatography (LC)/tandem mass spectrometry (MS/MS) analysis on pooled protein extracts from neovascular membranes obtained from PDR specimens and compared the results with those from non-vascular epiretinal membrane (ERM) specimens. We detected 226 distinct proteins in neovascular membranes and 154 in ERM. Among these proteins, 102 were specific to neovascular membranes and 30 were specific to ERM. We identified a candidate marker, periostin, as well as several known PDR markers such as pigment epithelium-derived factor (PEDF). We then performed RT-PCR using these markers. The expression of periostin was significantly up-regulated in proliferative membrane specimens. Periostin induces cell attachment and spreading and plays a role in cell adhesion. Proteomic analysis by LC/MS/MS, which permits accurate quantitative comparison, was useful in identifying new candidates such as periostin potentially involved in the pathogenesis of PDR.

  1. A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy

    PubMed Central

    Luo, Shasha; Wang, Furu; Shi, Chao; Wu, Zhifeng

    2016-01-01

    Aims: To shed light on the conflicting findings of the association between the methylenetetrahydrofolate reductase gene (MTHFR) 677C/T polymorphism and the risk of diabetic retinopathy (DR), a meta-analysis was conducted. Methods: A predefined search was performed on 1747 DR cases and 3146 controls from 18 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the sizes of overall and stratification effects of the MTHFR 677C/T polymorphism on the risk of DR, as appropriate. Results: Risks were evaluated by odds ratios (OR) with 95% confidence intervals (95% CI). We found a significant association between the MTHFR 677C/T polymorphism and the risk of DR for each genetic model (recessive model: OR = 1.67; 95% CI: 1.19–2.40 and dominant model: OR = 1.71; 95% CI: 1.28–2.28; respectively). In stratified analysis; we further found that the Asian group with both types of diabetes mellitus (DM) showed a significant association with genetic models (recessive model: OR = 2.16; 95% CI: 1.75–2.60 and dominant model: OR = 1.98; 95% CI: 1.42–2.76; respectively). Conclusions: Our study suggested that the MTHFR 677C/T polymorphism may contribute to DR development, especially in Asian populations. Prospective and additional genome-wide association studies (GWAS) are needed to clarify the real role of the MTHFR gene in determining susceptibility to DR. PMID:27517946

  2. Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C δ in a mouse model of diabetic retinopathy.

    PubMed

    Park, Jeongsook; Kim, Hwajin; Park, So Yun; Lim, Sun Woo; Kim, Yoon Sook; Lee, Dong Hoon; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Jeong, Bo-Young; Kwon, H Moo; Choi, Wan Sung

    2014-05-01

    Recent studies revealed that Tonicity-responsive enhancer binding protein (TonEBP) directly regulates the transcription of aldose reductase (AR), which catalyzes the first step of the polyol pathway of glucose metabolism. Activation of protein kinase C δ (PKCδ) is dependent on AR and it has been linked to diabetic complications. However, whether TonEBP affects expressions of AR and PKCδ in diabetic retinopathy was not clearly shown. In this study, we used TonEBP heterozygote mice to study the role of TonEBP in streptozotocin (STZ)-induced diabetic retinopathy. We performed immunofluorescence staining and found that retinal expressions of AR and PKCδ were significantly reduced in the heterozygotes compared to wild type littermates, particularly in ganglion cell layer. To examine further the effect of TonEBP reduction in retinal tissues, we performed intravitreal injection of TonEBP siRNA and confirmed the decrease in AR and PKCδ levels. In addition, we found that a proapoptotic factor, Bax level was reduced and a survival factor, Bcl2 level was increased after injection of TonEBP siRNA, indicating that TonEBP mediates apoptotic cell death. In parallel, TonEBP siRNA was applied to the in vitro human retinal pigment epithelial (ARPE-19) cells cultured in high glucose media. We have consistently found the decrease in AR and PKCδ levels and changes in apoptotic factors for survival. Together, these results clearly demonstrated that hyperglycemia-induced TonEBP plays a crucial role in increasing AR and PKCδ levels and leading to apoptotic death. Our findings suggest that TonEBP reduction is an effective therapeutic strategy for diabetic retinopathy. PMID:24631337

  3. Semaphorin3a Promotes Advanced Diabetic Nephropathy

    PubMed Central

    Aggarwal, Pardeep K.; Veron, Delma; Thomas, David B.; Siegel, Dionicio; Moeckel, Gilbert; Kashgarian, Michael

    2015-01-01

    The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN. PMID:25475434

  4. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats.

    PubMed

    Mitsuhashi, Junko; Morikawa, Shunichi; Shimizu, Kazuhiko; Ezaki, Taichi; Yasuda, Yoshiko; Hori, Sadao

    2013-01-01

    A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague-Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin-/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin-/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin-/type IV+ acellular strands to levels observed in the control group. However, the lectin-/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage. PMID:23178551

  5. Comparative effectiveness of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers in patients with type 2 diabetes and retinopathy