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Sample records for advanced diabetic retinopathy

  1. Advanced glycation end products and diabetic retinopathy.

    PubMed

    Milne, Ross; Brownstein, Seymour

    2013-06-01

    Retinopathy is a serious microvascular complication of diabetes and a major cause of blindness in young adults, worldwide. Early diabetic retinopathy is characterized by a loss of pericytes from retinal capillaries, the appearance of acellular capillaries and microaneurysms, and a breakdown of the blood-retinal barrier. In later stages, this can evolve into the proliferative phase in which there is neovascularization of the retina, which greatly increases the probability of vision loss. Advanced glycation end products (AGEs) which accumulate under hyperglycemic conditions are thought to play an important role in the pathogenesis of diabetic retinopathy. AGEs arise primarily by the modification of amine groups of proteins by reactive dicarbonyls such as methylglyoxal. Intracellular proteins including anti-oxidant enzymes, transcription factors and mitochondrial proteins are targets of dicarbonyl modification and this can modify their functional properties and thus compromise cellular physiology. Likewise, modification of extracellular proteins by dicarbonyls can impair cell adhesion and can generate ligands that can potentially bind to cell surface AGE receptors that activate pro-inflammatory signaling pathways. AGE inhibitors have been shown to provide protection in animal models of diabetic retinopathy and currently are being evaluated in clinical trials.

  2. Diabetic Retinopathy

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetic Retinopathy What Is Diabetic Retinopathy? Click for more information Can Cause Vision ... vision loss and even blindness can result. Other Diabetic Eye Diseases In addition to diabetic retinopathy, other ...

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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)

  8. Biomarkers in Diabetic Retinopathy.

    PubMed

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

    2015-01-01

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

  9. Diabetic Retinopathy

    MedlinePlus

    ... to permanent vision loss. What is diabetic macular edema (DME)? DME is the build-up of fluid (edema) in a region of the retina called the ... made to leaking blood vessels in areas of edema near the center of the macula. Laser burns ...

  10. The evaluation of retinal circulation in advanced diabetic retinopathy before and after panretinal laser photocoagulation by scanning laser opthalmoscope

    NASA Astrophysics Data System (ADS)

    Okano, Tadashi

    2005-07-01

    I investigated the effects of panretinal laser photocoagulation (PRP) on the velocity of retinal circulation in diabetic retinopathy. The retinal circulation was evaluated by means of rapid serial fluorescein angiography (FAG), employing scanning laser ophthalmoscope. FAG was conducted at the rate of 30 frames per seconds in video-tape. Disc-to-macula transit time (DMTT) was defined as the parameter to evaluate the retinal circulation. Diabetic 28 eyes with advanced diabetic retinopathy were examined to measure the DMTT before and after PRP. Normal 30 eyes used as control. Mean DMTT decreased from 9.8+/-1.5 seconds before PRP to 8.2+/-1.5 seconds after PRP in 28 diabetic eyes. The value with improvement after PRP was significantly shorter than the value before PRP ( p < 0.05 ). These values before and after PRP were significantly longer than that (3.7+/-0.7 seconds ) in normal 30 eyes ( p < 0.01 ). Retinal circulation is retarded in diabetic retinopathy. The retardation of retinal circulation in diabetic retinopathy improves after PRP, but the value after PRP can not recover until the control level. This study was performed to reveal therapeutic effect to panretinal laser photocoagulation (PRP) for the retardation of retinal circulation in diabetic retinopathy. I investigated the effects of PRP on the velocity of retinal circulation in patients with advanced diabetic retinopathy.

  11. 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

  12. Inflammation in Diabetic Retinopathy

    PubMed Central

    Tang, Johnny; Kern, Timothy S.

    2012-01-01

    Diabetes causes a number of metabolic and physiologic abnormalities in the retina, but which of these abnormalities contribute to recognized features of diabetic retinopathy (DR) is less clear. Many of the molecular and physiologic abnormalities that have been found to develop in the retina in diabetes are consistent with inflammation. Moreover, a number of anti-inflammatory therapies have been found to significantly inhibit development of different aspects of DR in animal models. Herein, we review the inflammatory mediators and their relationship to early and late DR, and discuss the potential of anti-inflammatory approaches to inhibit development of different stages of the retinopathy. We focus primarily on information derived from in vivo studies, supplementing with information from in vitro studies were important. PMID:21635964

  13. Diabetic retinopathy and systemic factors.

    PubMed

    Frank, Robert N

    2015-01-01

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

  14. Diabetic Retinopathy and Systemic Factors

    PubMed Central

    Frank, Robert N.

    2015-01-01

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

  15. Increased serum levels of the specific advanced glycation end product methylglyoxal-derived hydroimidazolone are associated with retinopathy in patients with type 2 diabetes mellitus.

    PubMed

    Fosmark, Dag Sigurd; Torjesen, Peter A; Kilhovd, Bente K; Berg, Tore J; Sandvik, Leiv; Hanssen, Kristian F; Agardh, Carl-David; Agardh, Elisabet

    2006-02-01

    Advanced glycation end products (AGEs) are thought to play a major pathogenic role in diabetic retinopathy. The most important AGE is unknown, but as increased serum methylglyoxal-derived hydroimidazolone has been demonstrated in patients with type 2 diabetes mellitus, the aim of the present study was to elucidate possible associations between serum levels of hydroimidazolone and retinopathy in patients with type 2 diabetes mellitus. We recruited 227 patients with type 2 diabetes mellitus and retinopathy ranging from none to proliferative. Level of retinopathy was determined from 7 standard field stereo photographs per eye according to the Early Treatment Diabetic Retinopathy Study. The patients were 66 +/- 11 years old, with a known diabetes duration of 14 +/- 9 years. Serum levels of hydroimidazolone were determined with a competitive immunoassay. Serum levels of hydroimidazolone were increased in nonproliferative (median, 4.50 U/mL; interquartile range, 3.69-5.77 U/mL) and proliferative retinopathy (median, 4.88 U/mL; interquartile range, 3.70-6.52 U/mL) compared with patients without retinopathy (median, 4.02 U/mL; interquartile range, 3.47-4.88 U/mL) (P = .008 and .002, respectively). There was no association between hydroimidazolone and hemoglobin A1c (r = 0.04, P = .57). In addition, patients with proliferative retinopathy and a relatively short known duration of diabetes, that is, less than the median of 14 years, had increased serum levels of hydroimidazolone (median, 6.91 U/mL; interquartile range, 4.70-8.91 U/mL) compared with those with nonproliferative retinopathy (median, 4.34; interquartile range, 3.86-5.53U/mL, P = .015). Serum levels of hydroimidazolone are increased in type 2 diabetic patients with retinopathy. This association is independent of hitherto known associated factors, such as hemoglobin A1c.

  16. Association of genetic variants in the receptor for advanced glycation end products gene with diabetic retinopathy

    PubMed Central

    Yu, Weihong; Yang, Jingyun; Sui, Wenda; Qu, Bin; Huang, Ping; Chen, Youxin

    2016-01-01

    Abstract Background: Diabetic retinopathy (DR) is a major sight-threatening diabetic complication. Previous studies have examined the association of DR with multiple genetic variants in the receptor for advanced glycation end products (RAGE) gene, with inconsistent results. Objective: To perform a systematic literature search and conduct meta-analyses to examine the association of genetic variants in RAGE with DR. Data sources: PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. Study eligibility criteria and participants: Studies were on human subjects; the studies were case–control ones and included subjects who had DR and those who did not have DR; and the studies provided genotype data for genetic variants in RAGE, separately for subjects who had and did not have DR, or provided odds ratios (ORs) and the 95% confidence intervals (CIs), or provided sufficient data for the calculation of OR and the 95% CI. Study appraisal and synthesis methods: We used OR as a measure of association, and used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I2, and publication bias was evaluated using Egger test. Results: A total of 13 studies met the eligibility criteria and were included in our analyses. We found that Gly82Ser was significantly associated with DR (OR = 2.40, 95% CI: 1.46–3.97; P = 0.001) using a recessive model. -374T/A also showed significant association with DR under a dominant model (OR = 1.21, 95% CI: 1.03–1.43; P = 0.023). We did not find a significant association of DR with other genetic variants in RAGE. Limitations: The number of included studies is small for some genetic variants; duration of diabetes varied across studies; most studies were conducted in Asia; and it is not clear whether the observed association can be generalized to other ethnicities; and we could not control for other potential confounding factors. Conclusions and implications of key findings: We found that Gly82Ser in RAGE

  17. Pharmacologic vitreolysis in diabetic retinopathy.

    PubMed

    El-Asrar, Ahmed M Abu; Al-Mezain, Hani S

    2011-03-01

    Diabetic retinopathy remains a major cause of worldwide preventable blindness. The vitreo-retinal interface plays a critical role in the pathogenesis of diabetic retinopathy. The term pharmacologic vitreolysis refers to the use of enzymes to liquefy the vitreous gel, and to induce posterior vitreous detachment (PVD). Intravitreal ovine hyaluronidase injection was effective in clearing vitreous hemorrhage. Several human case series demonstrated that intravitreal injection of autologous plasmin enzyme was a safe and effective adjunct to vitreous surgery for the treatment of diabetic macular edema and proliferative diabetic retinopathy. Recently, it was shown that intravitreal injection of plasmin enzyme without the performance of vitrectomy induced complete PVD and reduced macular thickening due to refractory diabetic macular edema.

  18. Diabetic Retinopathy and Diabetic Macular Edema.

    PubMed

    Cohen, Steven R; Gardner, Thomas W

    2016-01-01

    Diabetic retinopathy and diabetic macular edema result from chronic damage to the neurovascular structures of the retina. The pathophysiology of retinal damage remains uncertain but includes metabolic and neuroinflammatory insults. These mechanisms are addressed by intensive metabolic control of the systemic disease and by the use of ocular anti-inflammatory agents, including vascular endothelial growth factor inhibitors and corticosteroids. Improved understanding of the ocular and systemic mechanisms that underlie diabetic retinopathy will lead to improved means to diagnose and treat retinopathy and better maintain vision.

  19. Epigenetic modifications and diabetic retinopathy.

    PubMed

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

    2013-01-01

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

  20. Hypoxic viscosity and diabetic retinopathy.

    PubMed Central

    Rimmer, T; Fleming, J; Kohner, E M

    1990-01-01

    Diabetic and sickle retinopathy have features in common--for example, venous dilatation, microaneurysms, and capillary closure preceding neovascularisation. Bearing in mind that haemoglobin in poorly controlled diabetes is abnormal and that extremely low oxygen tensions (known to cause sickling) exist in the healthy cat retina, we wished to explore the possibility that diabetic blood, like that of sickle cell disease, may become more viscous when deoxygenated. To do this we measured whole blood viscosity, under oxygenated and deoxygenated conditions, of 23 normal persons, 23 diabetic patients without retinopathy, and 34 diabetic patients with retinopathy. The shear rate used was 230 s-1, which is similar to that thought to prevail in the major retinal veins. The viscosity of blood from normal persons, corrected for packed cell volume, did not change significantly on deoxygenation: mean 4.54 (SD 0.38) cps, versus, 4.57 (0.39) paired t test, p = 0.66. Similarly the blood from diabetics without retinopathy showed no change: 4.42 (0.45) versus 4.42 (0.30), p = 0.98; whereas the blood from patients with retinopathy changed from 4.82 (0.48) to 4.95 (0.63), p = 0.027. The hypoxic viscosity ratio (deoxygenated divided by oxygenated viscosity) correlated with total serum cholesterol (r = 0.44, p = 0.018) but not with HbA1, serum glucose, triglycerides, or age. A disproportionate increase in venous viscosity relative to arterial viscosity would lead to increased intraluminal and transmural pressure and therefore exacerbate leakage across capillary walls. PMID:2378855

  1. Recent Developments in Laser Treatment of Diabetic Retinopathy

    PubMed Central

    Yun, Samuel H.; Adelman, Ron A.

    2015-01-01

    Laser photocoagulation has been the mainstay of diabetic retinopathy treatment since its development in mid-20th century. With the advent of antivascular endothelial growth factor therapy, the role of laser therapy appeared to be diminished, however many advances in laser technology have been developed since. This review will describe recent advances in laser treatment of diabetic retinopathy including pattern scan laser, short-pulse duration and a reduced fluence laser, and navigated laser system for proliferative diabetic retinopathy and macular edema. PMID:25949072

  2. Epidemiological Issues in Diabetic Retinopathy

    PubMed Central

    Scanlon, Peter H; Aldington, Stephen J; Stratton, Irene M

    2013-01-01

    There is currently an epidemic of diabetes in the world, principally type 2 diabetes that is linked to changing lifestyle, obesity, and increasing age of the population. Latest estimates from the International Diabetes Federation (IDF) forecasts a rise from 366 million people worldwide to 552 million by 2030. Type 1 diabetes is more common in the Northern hemisphere with the highest rates in Finland and there is evidence of a rise in some central European countries, particularly in the younger children under 5 years of age. Modifiable risk factors for progression of diabetic retinopathy (DR) are blood glucose, blood pressure, serum lipids, and smoking. Nonmodifiable risk factors are duration, age, genetic predisposition, and ethnicity. Other risk factors are pregnancy, microaneurysm count in an eye, microaneurysm formation rate, and the presence of any DR in the second eye. DR, macular edema (ME), and proliferative DR (PDR) develop with increased duration of diabetes and the rates are dependent on the above risk factors. In one study of type 1 diabetes, the median individual risk for the development of early retinal changes was 9.1 years of diabetes duration. Another study reported the 25 year incidence of proliferative retinopathy among population-based cohort of type 1 patients with diabetes was 42.9%. In recent years, people with diabetes have lower rates of progression than historically to PDR and severe visual loss, which may reflect better control of glucose, blood pressure, and serum lipids, and earlier diagnosis. PMID:24339678

  3. The Danish Registry of Diabetic Retinopathy

    PubMed Central

    Andersen, Nis; Hjortdal, Jesper Østergaard; Schielke, Katja Christina; Bek, Toke; Grauslund, Jakob; Laugesen, Caroline Schmidt; Lund-Andersen, Henrik; Cerqueira, Charlotte; Andresen, Jens

    2016-01-01

    Aim of database To monitor the development of diabetic eye disease in Denmark and to evaluate the accessibility and effectiveness of diabetic eye screening programs with focus on interregional variations. Target population The target population includes all patients diagnosed with diabetes. Denmark (5.5 million inhabitants) has ~320,000 diabetes patients with an annual increase of 27,000 newly diagnosed patients. The Danish Registry of Diabetic Retinopathy (DiaBase) collects data on all diabetes patients aged ≥18 years who attend screening for diabetic eye disease in hospital eye departments and in private ophthalmological practice. In 2014–2015, DiaBase included data collected from 77,968 diabetes patients. Main variables The main variables provide data for calculation of performance indicators to monitor the quality of diabetic eye screening and development of diabetic retinopathy. Data with respect to age, sex, best corrected visual acuity, screening frequency, grading of diabetic retinopathy and maculopathy at each visit, progression/regression of diabetic eye disease, and prevalence of blindness were obtained. Data analysis from DiaBase’s latest annual report (2014–2015) indicates that the prevalence of no diabetic retinopathy, nonproliferative diabetic retinopathy, and proliferative diabetic retinopathy is 78%, 18%, and 4%, respectively. The percentage of patients without diabetic maculopathy is 97%. The proportion of patients with regression of diabetic retinopathy (20%) is greater than the proportion of patients with progression of diabetic retinopathy (10%). Conclusion The collection of data from diabetic eye screening is still expanding in Denmark. Analysis of the data collected during the period 2014–2015 reveals an overall decrease of diabetic retinopathy compared to the previous year, although the number of patients newly diagnosed with diabetes has been increasing in Denmark. DiaBase is a useful tool to observe the quality of screening

  4. 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.

  5. Pharmacologic therapies for diabetic retinopathy and diabetic macular edema.

    PubMed

    Rechtman, Ehud; Harris, Alon; Garzozi, Hanna J; Ciulla, Thomas A

    2007-12-01

    Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-aged population of most developed countries. The increasing number of persons with diabetes worldwide suggests that DR/DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in persons with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (ie, hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function, as these conditions have been identified as risk factors for both the development and progression of DR/DME. The non-pharmacologic interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease. Several biochemical mechanisms, including increased vascular endothelial growth factor production, protein kinase C beta activation, oxidative stress, and accumulation of intracellular sorbitol and advanced glycosylation end products, may contribute to the vascular disruptions that characterize DR/DME. The inhibition of these pathways holds the promise of the intervention for diabetic retinopathy with higher success rate and also at earlier, non-sight-threatening stages.

  6. Soluble receptor for advanced glycation end-product (sRAGE)/pentosidine ratio: a potential risk factor determinant for type 2 diabetic retinopathy.

    PubMed

    Ng, Zhi Xiang; Chua, Kek Heng; Iqbal, Tajunisah; Kuppusamy, Umah Rani

    2013-04-03

    This study aims to investigate potential diabetic retinopathy (DR) risk factors by evaluating the circulating levels of pentosidine, soluble receptor for advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited. Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement. DNR and DR patients showed significantly higher levels of plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients. Proliferative DR patients had significantly higher levels of plasma pentosidine, sRAGE, AOPP and sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level, long duration of diabetes and low sRAGE/pentosidine ratio were determined as the risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR.

  7. [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.

  8. Chlorpropamide alcohol flushing and diabetic retinopathy.

    PubMed

    Leslie, R D; Barnett, A H; Pyke, D A

    1979-05-12

    "Mason-type" diabetics (mild diabetes which is dominantly inherited) are relatively free of retinopathy. Alcohol almost invariably causes facial flushing in these patients when they are given chlorpropamide (chlorpropamide alcohol flush, C.P.A.F.). 291 non-insulin-dependent diabetics were examined to see whether there was a difference in frequency of retinopathy between C.P.A.F. positive and negative cases who were of comparable age and duration of diabetes. Retinopathy was commoner and often severe in CPAF negative patients. Blindness from retinopathy was almost confined to C.P.A.F.-negative cases. Lens opacities, on the other hand, were equally common in both groups. Since C.P.A.F. is an inherited trait, retinopathy in non-insulin-dependent diabetics is to a considerable extent, although not entirely, determined by genetic factors.

  9. Risk Factors for the Development and Progression of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Advanced Diabetic Retinopathy

    PubMed Central

    Yun, Kyung-Jin; Kim, Hye Ji; Kim, Mee Kyoung; Kwon, Hyuk-Sang; Baek, Ki-Hyun; Roh, Young Jung

    2016-01-01

    Background Some patients with type 2 diabetes mellitus (T2DM) do not develop diabetic kidney disease (DKD) despite the presence of advanced diabetic retinopathy (DR). We aimed to investigate the presence of DKD and its risk factors in patients with T2DM and advanced DR. Methods We conducted a cross-sectional study in 317 patients with T2DM and advanced DR. The phenotypes of DKD were divided into three groups according to the urine albumin/creatinine ratio (uACR, mg/g) and estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): no DKD (uACR <30 and eGFR ≥60), non-severe DKD (uACR ≥30 or eGFR <60), and severe DKD (uACR ≥30 and eGFR <60). Mean systolic and diastolic blood pressure, mean glycosylated hemoglobin (HbA1c) level, and HbA1c variability (standard deviation [SD] of serial HbA1c values or HbA1c-SD) were calculated for the preceding 2 years. Results The prevalence of no DKD, non-severe DKD, and severe DKD was 37.2% (n=118), 37.0% (n=117), and 25.8% (n=82), respectively. HbA1c-SD and the triglyceride/high density lipoprotein cholesterol (TG/HDL-C) ratio correlated positively with uACR and negatively with eGFR. Multiple linear regression analyses showed that the HbA1c-SD and TG/HDL-C ratio were significantly related with eGFR. Multiple logistic regression analyses after adjusting for several risk factors showed that HbA1c-SD and the TG/HDL-C ratio were significant risk factors for severe DKD. Conclusion The prevalence of DKD was about 60% in patients with T2DM and advanced DR. HbA1c variability and TG/HDL-C ratio may affect the development and progression of DKD in these patients. PMID:27766790

  10. Diaretinopathy database –A Gene database for diabetic retinopathy

    PubMed Central

    Vidhya, Gopalakrishnan; Anusha, Bhaskar

    2014-01-01

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

  11. Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy.

    PubMed

    Gong, Xiaoming; Rubin, Lewis P

    2015-04-15

    Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are important causes of blindness among children and working-age adults, respectively. The development of both diseases involves retinal microvascular degeneration, vessel loss and consequent hypoxic and inflammatory pathologic retinal neovascularization. Mechanistic studies have shown that oxidative stress and subsequent derangement of cell signaling are important factors in disease progression. In eye and vision research, role of the dietary xanthophyll carotenoids, lutein and zeaxanthin, has been more extensively studied in adult onset macular degeneration than these other retinopathies. These carotenoids also may decrease severity of ROP in preterm infants and of DR in working-age adults. A randomized controlled clinical trial of carotenoid supplementation in preterm infants indicated that lutein has functional effects in the neonatal eye and is anti-inflammatory. Three multicenter clinical trials all showed a trend of decreased ROP severity in the lutein supplemented group. Prospective studies on patients with non-proliferative DR indicate serum levels of lutein and zeaxanthin are significantly lower in these patients compared to normal subjects. The present review describes recent advances in lutein and zeaxanthin modulation of oxidative stress and inflammation related to ROP and DR and discusses potential roles of lutein/zeaxanthin in preventing or lessening the risks of disease initiation or progression.

  12. Automated static perimetry to evaluate diabetic retinopathy.

    PubMed Central

    Federman, J L; Lloyd, J

    1984-01-01

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

  13. Polyunsaturated fatty acids and diabetic retinopathy.

    PubMed Central

    Howard-Williams, J; Patel, P; Jelfs, R; Carter, R D; Awdry, P; Bron, A; Mann, J I; Hockaday, T D

    1985-01-01

    One hundred and forty nine diabetic patients were ophthalmologically assessed seven years after randomisation to a low carbohydrate or modified fat diet (rich in linoleic acid). Glycaemic control, regardless of the type of diet, was a major determinant of the development of retinopathy. Poorly controlled patients (haemoglobin A1c greater than 8%) with low levels of linoleic acid in cholesterol ester had a significantly greater frequency of retinopathy than well controlled patients or patients with similarly unsatisfactory control but higher levels of linoleic acid. The findings support an earlier suggestion that linoleic acid might protect against diabetic retinopathy. PMID:3965024

  14. [Diabetic retinopathy complications--12-year retrospective study].

    PubMed

    Ignat, Florica; Davidescu, Livia

    2002-01-01

    It is analyzed, on a retrospective study on 12 years, the incidence of diabetus melitus cases, hospitalized in the Ophthalmologic Clinic from Craiova with special mention to the frequency of the diabetic retinopathy, of it's complications and in an accordance to other general diseases, especially cardiovascular's, which contributes to the aggravation of the diabetic ocular in juries evolution. The study underlines the high incidence of the new founded cases with diabetus melitus in complicated diabetes retinopathy stage; the high frequency of ocular complications is explained, according to our statistic facts and through an insufficient treatment, sometimes incorrect and many other cases total neglected by the patients.

  15. Retinal Imaging Techniques for Diabetic Retinopathy Screening

    PubMed Central

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

    2016-01-01

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

  16. Screening Diabetic Retinopathy Through Color Retinal Images

    NASA Astrophysics Data System (ADS)

    Li, Qin; Jin, Xue-Min; Gao, Quan-Xue; You, Jane; Bhattacharya, Prabir

    Diabetic Retinopathy (DR) is a common complication of diabetes that damages the eye's retina. Recognition DR as early as possible is very important to protect patients' vision. We propose a method for screening DR and distin-guishing Prolifetive Diabetic Retinopathy (PDR) from Non-Prolifetive Retino-pathy (NPDR) automatatically through color retinal images. This method evaluates the severity of DR by analyzing the appearnce of bright lesions and retinal vessel patterns. The bright lesions are extracted through morphlogical re-consturction. After that, the retinal vessels are automatically extracted using multiscale matched filters. Then the vessel patterns are analyzed by extracting the vessel net density. The experimental results domonstrate that it is a effective solution to screen DR and distinguish PDR from NPDR by only using color retinal images.

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

    PubMed Central

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

    2013-01-01

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

  18. Automated Early Detection of Diabetic Retinopathy

    PubMed Central

    Abràmoff, Michael D.; Reinhardt, Joseph M.; Russell, Stephen R.; Folk, James C.; Mahajan, Vinit B.; Niemeijer, Meindert; Quellec, Gwénolé

    2010-01-01

    Purpose To compare the performance of automated diabetic retinopathy (DR) detection, using the algorithm that won the 2009 Retinopathy Online Challenge Competition in 2009, (‘Challenge2009’) against that of the one currently used in EyeCheck, a large computer-aided early DR detection project. Design Evaluation of diagnostic test or technology. Participants Fundus photographic sets, consisting of two fundus images from each eye, were evaluated from 16,670 patient visits of 16,670 people with diabetes who had not previously been diagnosed with DR. Methods The fundus photographic set from each visit was analyzed by a single retinal expert; 793 of the 16,770 sets were classified as containing more than minimal DR (threshold for referral). The outcomes of the two algorithmic detectors were applied separately to the dataset and compared by standard statistical measures. Main Outcome Measures The area under the Receiver Operating Characteristic curve (AUC), a measure of the sensitivity and specificity of DR detection. Results Agreement was high, and exams containing more than minimal DR were detected with an AUC of 0.839 by the ‘Eyecheck’ algorithm and an AUC of 0.821 for ‘Challenge2009’, a statistically non-significant difference (z-score 1.91). If either of the algorithms detected DR in combination, AUC for detection was 0.86, the same as the theoretically expected maximum. At 90% sensitivity, the specificity of the ‘EyeCheck’ algorithm was 47.7% and the ‘Challenge2009’ algorithm, 43.6%. Conclusions DR detection algorithms appear to be maturing, and further improvements in detection performance cannot be differentiated from best clinical practices, because the performance of competitive algorithm development has now reached the human intra-reader variability limit. Additional validation studies on larger, well-defined, but more diverse populations of patients with diabetes are urgently needed, anticipating cost-effective early detection of DR in

  19. Neurodegeneration and neuroprotection in diabetic retinopathy.

    PubMed

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

    2013-01-28

    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.

  20. 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

  1. Biomarkers in Diabetic Retinopathy and the Therapeutic Implications

    PubMed Central

    Zorena, Katarzyna; Raczyńska, Dorota; Raczyńska, Krystyna

    2013-01-01

    The main problem both in type 1 (T1DM) and type 2 (T2DM) diabetes is the development of chronic vascular complications encompassing micro- as well as macrocirculation. Chronic complications lower the quality of life, lead to disability, and are the cause of premature death in DM patients. One of the chronic vascular complications is a diabetic retinopathy (DR) which leads to a complete loss of sight in DM patients. Recent trials show that the primary cause of diabetic retinopathy is retinal neovascularization caused by disequilibrium between pro- and antiangiogenic factors. Gaining knowledge of the mechanisms of action of factors influencing retinal neovascularization as well as the search for new, effective treatment methods, especially in advanced stages of DR, puts special importance on research concentrating on the implementation of biological drugs in DR therapy. At present, it is antivascular endothelial growth factor and antitumor necrosis factor that gain particular significance. PMID:24311895

  2. Severe diabetic retinopathy at presentation in a young man.

    PubMed Central

    Morris, G. C.; James, R. A.; Powell, R. G.; Jones, M. K.

    1991-01-01

    A 22 year old man presented with a severe ischaemic diabetic retinopathy and, in spite of photocoagulation therapy, was blind in one eye 16 months after diagnosis. Four similar cases of aggressive diabetic retinopathy are reviewed. There is increasing evidence that a small group of young men with insulin dependent diabetes (IDD) may develop severe diabetic retinopathy at, or soon after, diagnosis. Images Figure 1 PMID:1904157

  3. Raman spectroscopy of human vitreous collagen in diabetic retinopathy

    NASA Astrophysics Data System (ADS)

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

    1992-08-01

    In diabetes 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 vitreous degeneration and the progression of proliferative diabetic retinopathy. Previous studies have demonstrated early glycation and advanced endproducts in the vitreous of humans with proliferative diabetic retinopathy. 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. The results demonstrated substantial changes in diabetic vitreous collagen resulting from glycation, most likely advanced glycation endproducts. 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 non-enzymatic glycation and monitor the response to therapy.

  4. Argon laser photo-coagulation complications in diabetic retinopathy.

    PubMed

    Pavljasević, Suzana; Pranjić, Nurka; Sarajlić, Dzevdet

    2004-05-01

    Diabetic retinopathy is a disease based on vascular genesis that begins as microangiopathy and develops into macroangioapthy preceded by fibroproliferation changes. According to histo- pathological changes, diabetic retinopathy is divided into nonproliferative, pre-proliferative and proliferative diabetic retinopathy. Possibilities and needs for photo-coagulation in the earlier and later changes in retina reduce the meaning of conservative treatment. Laser photo-coagulation with therapeutical may cause unwanted and damaging effects, as well. Complications diagnosed in diabetic retinopathy, such as cataract, secondary glaucoma, central retinal vein thrombosis, haemophthalmus, are much more frequent in patients with laser photo-coagulation treatment.

  5. 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

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

    PubMed Central

    Oellers, Patrick; Mahmoud, Tamer H.

    2016-01-01

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

  7. 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.

  8. Effectiveness of panretinal photocoagulation in severe diabetic retinopathy

    NASA Astrophysics Data System (ADS)

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

    1999-02-01

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

  9. Visual complications in diabetes mellitus: beyond retinopathy.

    PubMed

    Khan, A; Petropoulos, I N; Ponirakis, G; Malik, R A

    2017-04-01

    Diabetic retinopathy is the most common cause of vision loss in people with diabetes mellitus; however, other causes of visual impairment/loss include other retinal and non-retinal visual problems, including glaucoma, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataracts. Additionally, when a person with diabetes complains of visual disturbance despite a visual acuity of 6/6, abnormalities in refraction, contrast sensitivity, straylight and amplitude of accommodation should be considered. We review and highlight these visual problems for physicians who manage people with diabetes to ensure timely referral and treatment to limit visual disability, which can have a significant impact on daily living, especially for those participating in sports and driving.

  10. Diabetic Retinopathy: Vascular and Inflammatory Disease

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. 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)

  13. 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.

  14. Inflammation and pharmacological treatment in diabetic retinopathy.

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

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

  16. Is medical treatment for diabetic retinopathy still an unreal dream?

    PubMed

    Giusti, C

    2002-12-01

    Diabetic retinopathy is a highly specific vascular complication of both type 1 and type 2 diabetes, estimated to be the most frequent cause of new cases of blindness in the working population of the Western world. The prevalence of retinopathy is strongly related to the duration of diabetes and glycemic control, even though a multifactorial pathogenesis should be probably considered in genetically susceptible subjects. Intensive diabetes management, with the goal of achieving near-normal glycemia, has been shown to prevent and/or delay the onset of diabetic retinopathy and laser photocoagulation has an established clinical efficacy in preventing visual loss. However, as laser scars always destroy the retinal anatomy permanently, a medical approach to nonproliferative retinopathy should be preferred if its clinical efficacy could be demonstrated. In this paper, recently published reports supporting this hypothesis are reviewed and their conclusions critically discussed.

  17. 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

  18. Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms.

    PubMed

    Csősz, Éva; Deák, Eszter; Kalló, Gergő; Csutak, Adrienne; Tőzsér, József

    2017-01-06

    Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness among patients with diabetes. The appearance and the severity of the symptoms correlate with the duration of diabetes and poor blood glucose level management. Diabetic retinopathy is also categorized as a chronic low-level inflammatory disease; the high blood glucose level promotes the accumulation of the advanced glycation end products and leads to the stimulation of monocytes and macrophages. Examination of protein level alterations in tears using state-of the art proteomics techniques have identified several proteins as possible biomarkers for the different stages of the diabetic retinopathy. Some of the differentially expressed tear proteins have a role in the barrier function of tears linking the diabetic retinopathy with another eye complication of diabetes, namely the diabetic keratopathy resulting in impaired wound healing. Understanding the molecular events leading to the eye complications caused by hyperglycemia may help the identification of novel biomarkers as well as therapeutic targets in order to improve quality of life of diabetic patients.

  19. 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.

  20. 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

    2015-12-29

    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.

  1. 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

  2. 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.

  3. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies.

    PubMed

    Ciulla, Thomas A; Amador, Armando G; Zinman, Bernard

    2003-09-01

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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

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

    PubMed Central

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

    2014-01-01

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

  10. 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.

  11. The Prevalence of Diabetic Retinopathy Among Known Diabetic Population in Nepal.

    PubMed

    Mishra, S K; Pant, B P; Subedi, P

    2016-01-01

    Background The worldwide prevalence of diabetic retinopathy (DR) was found to be 34.6%. WHO estimates that DR is responsible for 4.8% of the 37 million cases of blindness throughout the world. In a study undertaken in urban population in Nepal, M.D. Bhattarai found the prevalence of diabetes among people aged 20 years and above to be 14.6% and the prevalence among people aged 40 years and above to be 19%. Studies on DR, to our knowledge, have mostly been hospital based in Nepal. Little information is available about prevalence of DR at the community level in Nepal. Objective To investigate the prevalence of diabetic retinopathy and associated risk factors among known diabetic population of Nepal. Method A descriptive cross sectional study was conducted among individuals aged 30 and more using cluster sampling method. The study sites were Kathmandu metropolitan city and Birgunj sub-metropolitan city. A sample size of 5400 was calculated assuming 5% prevalence rate with 95% confidence level, 5% worst acceptable level and 1.5 cluster sampling design effect. Study participants were interviewed, anthropometric measurements and fundus photograph was taken from participants with diabetes. Fundus photographs were used to grade retinopathy. Result Around 12% of the respondents were diabetic, mean age 55.43±11.86 years, of which slightly more than half were females (50.2%). Among these diabetic respondents 9.9% had some forms of diabetic retinopathy, mean age 54.08±10.34 years, 56.7% were male. When severe grade of retinopathy in any eye was considered as overall grade of retinopathy for the individual, prevalence of Non-proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy and complete vision loss was found to be 9.1%, 0.5% and 0.3%. Prevalence of Diabetic Macular Edema was 5.5%. Duration of diabetes, family history of diabetes and blood pressure at the day of survey was found to be associated with having any retinopathy. Conclusion Diabetic retinopathy

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

    PubMed

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

    2016-08-01

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

  13. 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

  14. Screening for diabetic retinopathy and nephropathy in patients with diabetes: a nationwide survey in Korea.

    PubMed

    Byun, Sang-Ho; Ma, Seung Hyun; Jun, Jae Kwan; Jung, Kyu-Won; Park, Boyoung

    2013-01-01

    This study was performed to identify factors associated with screening for diabetic retinopathy and nephropathy. Data from the Korean National Health and Nutrition Examination Survey between 2007 and 2009 were analyzed. Of 24,871 participants, 1,288 patients diagnosed with diabetes at ≥30 years of age were included. 36.3% received screening for diabetic retinopathy, and 40.5% received screening for diabetic nephropathy during the previous year. Patients living in rural areas, those with less education, those who had not received education about diabetes care, and those who did not receive medical care for diabetes were screened less often for retinopathy or nephropathy. Patients with poorer self-reported health status were screened more often. Occupation, smoking status, and diabetes duration were associated with retinopathy screening. Lower family income was associated with decreased nephropathy screening. Receiving education about diabetes care and receiving medical care for diabetes were significant factors in patients with a shorter duration of diabetes (the significant odds ratio [OR] of not receiving education varied between 0.27 and 0.51, and that of not receiving medical care varied between 0.34 and 0.42). Sociodemographic factors and health-related factors as well as education and medical care influenced screening for diabetic complications among those with a longer duration of diabetes (for retinopathy and nephropathy, the significant OR of living in a rural area varied between 0.56 and 0.61; for retinopathy, the significant OR of current smokers was 0.55, and the p-trend of subjective health status was <0.001; for nephropathy, the significant OR of a monthly household income of <3000 dollars was 0.61 and the p-trends of education and subjective health status were 0.030 and 0.007, respectively). Efforts to decrease sociodemographic disparities should be combined with education about diabetes care to increase the screening, especially for those with a

  15. 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

  16. 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.

  17. 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

  18. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. 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

  1. Vitamin Status as a Determinant of Serum Homocysteine Concentration in Type 2 Diabetic Retinopathy

    PubMed Central

    Raptis, Athanasios; Apergis, George; Dimitriadis, George; Vergados, Ioannis; Theodossiadis, Panagiotis

    2014-01-01

    We investigated the association of serum homocysteine levels and vitamin status with type 2 diabetic retinopathy. This study included 65 patients with and 75 patients without diabetic retinopathy. Patients with diabetic retinopathy had significantly higher serum homocysteine levels (P < 0.001), higher prevalence of hyperhomocysteinemia (P < 0.001), lower serum folic acid (P < 0.001), and vitamin B12 (P = 0.014) levels than those without diabetic retinopathy. Regression analysis revealed that homocysteine was an independent risk factor for diabetic retinopathy and there was a threshold in its serum level (13.7 μmol/L), above which the risk of diabetic retinopathy greatly increases (OR = 1.66, P = 0.001). Folic acid was associated with decreased odds for diabetic retinopathy (OR = 0.73, P < 0.001). There was a threshold in serum vitamin B12 level (248.4 pg/mL), below which serum homocysteine concentration significantly increases with decreasing serum vitamin B12 (P = 0.003). Our findings suggest that hyperhomocysteinemia is an independent risk factor for the development and progression of diabetic retinopathy. Decreased serum levels of folic acid and vitamin B12, through raising serum homocysteine concentrations, may also affect the diabetic retinopathy risk. PMID:25006590

  2. Autoimmune destruction of pericytes as the cause of diabetic retinopathy.

    PubMed

    Adams, Duncan D

    2008-06-01

    In diabetic retinopathy, collapse of the retinal vasculature is associated with loss of the pericytes. These are contractile cells that together with endothelial cells form the terminal arterioles of the retina. The cause of the loss of pericytes is not known. Recently, it has been discovered that type 1 diabetes is caused by forbidden clones of cytotoxic T lymphocytes, which destroy the insulin-making cells with exquisite specificity. In the light of this, I postulate that an antigenically-related forbidden clone of cytotoxic T lymphocytes selectively destroys the pericytes and that this is the cause of the vascular collapse of diabetic retinopathy. If this is so, the therapeutic implications are immense, involving a switch from ineffectual tight glycemic control to immunotherapy. This is already used as immunosuppression to prevent organ transplant rejection, and as the immune ablation and autologous bone marrow cell reconstitution that has saved the lives of patients with lethally-severe scleroderma. Once the pericyte surface auto-antigen for the T lymphocytes has been isolated, selective destruction of the pathogenic T lymphocytes would be possible by manufacture and use of cytotoxic auto-antigen complexes, which arrests progression of the retinopathy.

  3. Pattern Visual Evoked Potential Changes in Diabetic Patients without Retinopathy

    PubMed Central

    Sungur, Gulten; Yakin, Mehmet; Unlu, Nurten; Balta, Oyku Bezen; Ornek, Firdevs

    2017-01-01

    Purpose. To assess the different check sizes of pattern visual evoked potential (PVEP) in diabetic patients without retinopathy according to HbA1c levels and diabetes duration. Methods. Fifty-eight eligible patients with type 2 diabetes mellitus and 26 age- and sex-matched healthy controls were included in the study. Only the right eye of each patient was analyzed. All of the patients underwent a comprehensive ophthalmic examination, and the PVEPs were recorded. Results. There was a statistically significant difference in P100 latency in 1-degree check size and in N135 latency in 2-degree check size between controls and patient groups which have different HbA1c levels. There were statistically significant, positive, and weak correlations with diabetes duration and P100 latency in 7-minute and 15-minute check sizes and N135 latency in 15-minute check size. Conclusions. It was showed that there were prolongations in P100 latency only in 1-degree check size and in N135 only in 2-degree check size in diabetic patients without retinopathy. There was statistically significant correlation between diabetes duration and P100 and N135 latencies in different check sizes. PMID:28392940

  4. 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.

  5. Peripheral Blood Mitochondrial DNA Damage as a Potential Noninvasive Biomarker of Diabetic Retinopathy

    PubMed Central

    Mishra, Manish; Lillvis, John; Seyoum, Berhane; Kowluru, Renu A.

    2016-01-01

    Purpose In the development of diabetic retinopathy, retinal mitochondria become dysfunctional, and mitochondrial DNA (mtDNA) is damaged. Because retinopathy is a progressive disease, and circulating glucose levels are high in diabetes, our aim was to investigate if peripheral blood mtDNA damage can serve as a potential biomarker of diabetic retinopathy. Methods Peripheral blood mtDNA damage was investigated by extended-length PCR in rats and mice, diabetic for 10 to 12 months (streptozotocin-induced, type 1 model), and in 12- and 40-week-old Zucker diabetic fatty rats (ZDF, type 2). Mitochondrial copy number (in gDNA) and transcription (in cDNA) were quantified by qPCR. Similar parameters were measured in blood from diabetic patients with/without retinopathy. Results Peripheral blood from diabetic rodents had significantly increased mtDNA damage and decreased copy numbers and transcription. Lipoic acid administration in diabetic rats, or Sod2 overexpression or MMP-9 knockdown in mice, the therapies that prevent diabetic retinopathy, also ameliorated blood mtDNA damage and restored copy numbers and transcription. Although blood from 40-week-old ZDF rats had significant mtDNA damage, 12-week-old rats had normal mtDNA. Diabetic patients with retinopathy had increased blood mtDNA damage, and decreased transcription and copy numbers compared with diabetic patients without retinopathy and nondiabetic individuals. Conclusions Type 1 diabetic rodents with oxidative stress modulated by pharmacologic/genetic means, and type 2 animal model and patients with/without diabetic retinopathy, demonstrate a strong relation between peripheral blood mtDNA damage and diabetic retinopathy, and suggest the possibility of use of peripheral blood mtDNA as a noninvasive biomarker of diabetic retinopathy. PMID:27494345

  6. Mitochondrial Haplogroups Affect Severity But Not Prevalence of Diabetic Retinopathy

    PubMed Central

    Bregman, Jana A.; Herren, David J.; Estopinal, Christopher B.; Chocron, Isaac M.; Harlow, Paula A.; Warden, Cassandra; Brantley, Milam A.; Samuels, David C.

    2017-01-01

    Purpose We previously reported European mitochondrial haplogroup H to be a risk factor for and haplogroup UK to be protective against proliferative diabetic retinopathy (PDR) among Caucasian patients with diabetic retinopathy (DR). The purpose of this study was to determine whether these haplogroups are also associated with the risk of having DR among Caucasian patients with diabetes. Methods Deidentified medical records for 637 Caucasian patients with diabetes (223 with DR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An additional 197 Caucasian patients with diabetes (98 with DR) were enrolled from the Vanderbilt Eye Institute (VEI). We tested for an association between European mitochondrial haplogroups and DR status. Results The percentage of diabetes patients with DR did not differ across the haplogroups (P = 0.32). The percentage of patients with nonproliferative DR (NPDR; P = 0.0084) and with PDR (P = 0.027) significantly differed across the haplogroups. In logistic regressions adjusting for sex, age, diabetes type, duration of diabetes, and hemoglobin A1c, neither haplogroup H nor haplogroup UK had a significant effect on DR compared with diabetic controls. Haplogroup UK was a significant risk factor (OR = 1.72 [1.13–2.59], P = 0.010) for NPDR compared with diabetic controls in the unadjusted analysis, but not in the adjusted analysis (OR = 1.29 [0.79–2.10], P = 0.20). Conclusions Mitochondrial haplogroups H and UK were associated with severity, but not presence, of DR. These data argue that the effect of these haplogroups is related to ischemia and neovascularization, the defining features of PDR. PMID:28245487

  7. 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.

  8. 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

  9. 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

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

    PubMed

    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.

  11. 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

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

    PubMed Central

    Reinherz, Benjamin J.; Rubin, Jeffrey S.

    2016-01-01

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

  13. The impact of improved glycaemic control with GLP-1 receptor agonist therapy on diabetic retinopathy.

    PubMed

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

    2014-03-01

    Rapid improvement in glycaemic control with GLP-1 receptor agonist (RA) therapy has been reported to be associated with significant progression of diabetic retinopathy. This deterioration is transient, and continuing GLP-1 RA treatment is associated with reversal of this phenomenon. Pre-existent maculopathy, higher grade of retinopathy and longer duration of diabetes may be risk factors for persistent deterioration.

  14. Diabetic retinopathy in sub-Saharan Africa: meeting the challenges of an emerging epidemic

    PubMed Central

    2013-01-01

    Background Sub-Saharan Africa faces an epidemic of diabetes. Diabetes causes significant morbidity including visual loss from diabetic retinopathy, which is largely preventable. In this resource-poor setting, health systems are poorly organized to deliver chronic care with multiple system involvement. The specific skills and resources needed to manage diabetic retinopathy are scarce. The costs of inaction for individuals, communities and countries are likely to be high. Discussion Screening for and treatment of diabetic retinopathy have been shown to be effective, and cost-effective, in resource-rich settings. In sub-Saharan Africa, clinical services for diabetes need to be expanded with the provision of effective, integrated care, including case-finding and management of diabetic retinopathy. This should be underpinned by a high quality evidence base accounting for differences in diabetes types, resources, patients and society in Africa. Research must address the epidemiology of diabetic retinopathy in Africa, strategies for disease detection and management with laser treatment, and include health economic analyses. Models of care tailored to the local geographic and social context are most likely to be cost effective, and should draw on experience and expertise from other continents. Research into diabetic retinopathy in Africa can drive the political agenda for service development and enable informed prioritization of available health funding at a national level. Effective interventions need to be implemented in the near future to avert a large burden of visual loss from diabetic retinopathy in the continent. Summary An increase in visual loss from diabetic retinopathy is inevitable as the diabetes epidemic emerges in sub-Saharan Africa. This could be minimized by the provision of case-finding and laser treatment, but how to do this most effectively in the regional context is not known. Research into the epidemiology, case-finding and laser treatment of diabetic

  15. Scanning laser entoptic perimetry for the detection of visual defects associated with diabetic retinopathy

    PubMed Central

    El‐Bradey, M; Plummer, D J; Uwe‐Bartsch, D; Freeman, W R

    2006-01-01

    Aim To determine the sensitivity and specificity of entoptic perimetry for diagnosing diabetic retinopathy at all levels of severity. Methods A prospective clinical study at the Shiley Eye Center, University of California, and San Diego. 30 patients with photographically documented diabetic retinopathy and 24 controls with a similar age distribution. Sensitivity and specificity of entoptic perimetry were computed for detecting clinically significant macular oedema within the central 120 degree radius of the fovea compared to fundus photographs. Results Entoptic perimetry can detect clinically significant diabetic retinopathy with a sensitivity of 0.88 and specificity of 1.00. Entoptic perimetry can detect the earliest stages of diabetic retinopathy with a sensitivity of 0.86. Conclusion Scanning laser entoptic perimetry is an effective tool for detecting visual function loss caused by diabetic retinopathy. PMID:16361659

  16. Heritability of the Severity of Diabetic Retinopathy: The FIND-Eye Study

    PubMed Central

    Arar, Nedal H.; Freedman, Barry I.; Adler, Sharon G.; Iyengar, Sudha K.; Chew, Emily Y.; Davis, Mathew D.; Satko, Scott G.; Bowden, Donald W.; Duggirala, Ravi; Elston, Robert C.; Guo, Xiuxing; Hanson, Robert L.; Igo, Robert P.; Ipp, Eli; Kimmel, Paul L.; Knowler, William C.; Molineros, Julio; Nelson, Robert G.; Pahl, Madeleine V.; Quade, Shannon R. E.; Rasooly, Rebekah S.; Rotter, Jerome I.; Saad, Mohammed F.; Scavini, Marina; Schelling, Jeffrey R.; Sedor, John R.; Shah, Vallabh O.; Zager, Philip G.; Abboud, Hanna E.

    2008-01-01

    PURPOSE Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. METHODS The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib–sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. RESULTS This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (χ2 = 658.14, df = 20; P < 0.0001). The sib–sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the

  17. Asymmetric severity of diabetic retinopathy in Waardenburg syndrome

    PubMed Central

    Kashima, Tomoyuki; Akiyama, Hideo; Kishi, Shoji

    2011-01-01

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

  18. Left ventricular systolic function in selected type 1 diabetic patients with or without diabetic retinopathy and microalbuminuria.

    PubMed

    Bućan, Kajo; Bojić, Lovro; Fabijanić, Damir; Galetović, Davor; Čapkun, Vesna; Utrobičić, Dobrila Karlica; Bućan, Ivona

    2014-12-01

    Vascular endothelial dysfunction is a basic etiologic factor for the development of late clinical complications in patients with diabetes mellitus type 1, such as diabetic retinopathy, diabetic nephropathy (which is characterized at the very beginning by microalbuminuria), and left ventricular cardiac dysfunction. The aims of this study were to determine the prevalence of asymptomatic left ventricular systolic dysfunction in patients with diabetes mellitus type 1 and with or without diabetic retinopathy and microalbuminuria, and to correlate the duration of diabetes with the dynamics of diabetic retinopathy, microalbuminuria and asymptomatic left ventricular dysfunction development in these patients. One-hundred and twenty selected patients with diabetes mellitus type 1 were examined by ophthalmologist and cardiologist. All patients underwent ergometric testing and two-dimensional (2-D) echocardiography with pulsed Doppler. Patients were divided into three groups according to their fundus findings and microalbuminuria: (1) patients without diabetic retinopathy and without microalbuminuria (n = 40); (2) patients with diabetic retinopathy without microalbuminuria (n = 40); and (3) patients with diabetic retinopathy and microalbuminuria (n = 40). All three groups of patients with diabetes mellitus type 1 (with low cardiovascular risk, regulated blood sugar, and without diabetic neuropathy) had echocardiographic values in the normal range. We found no statistically significant correlation between the duration of diabetes mellitus type 1 and echocardiographic values.

  19. Diabetic Retinopathy Clinical Practice Guidelines: Customized for Iranian Population

    PubMed Central

    Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Azarmina, Mohsen; Moradian, Siamak; Entezari, Morteza; Nourinia, Ramin; Ahmadieh, Hamid; Shirvani, Armin; Shahraz, Saeid; Ramezani, Alireza; Dehghan, Mohammad Hossein; Shahsavari, Mohsen; Soheilian, Masoud; Nikkhah, Homayoun; Ziaei, Hossein; Behboudi, Hasan; Farrahi, Fereydoun; Falavarjani, Khalil Ghasemi; Parvaresh, Mohammad Mehdi; Fesharaki, Hamid; Abrishami, Majid; Shoeibi, Nasser; Rahimi, Mansour; Javadzadeh, Alireza; Karkhaneh, Reza; Riazi-Esfahani, Mohammad; Manaviat, Masoud Reza; Maleki, Alireza; Kheiri, Bahareh; Golbafian, Faegheh

    2016-01-01

    Purpose: To customize clinical practice guidelines (CPGs) for management of diabetic retinopathy (DR) in the Iranian population. Methods: Three DR CPGs (The Royal College of Ophthalmologists 2013, American Academy of Ophthalmology [Preferred Practice Pattern 2012], and Australian Diabetes Society 2008) were selected from the literature using the AGREE tool. Clinical questions were designed and summarized into four tables by the customization team. The components of the clinical questions along with pertinent recommendations extracted from the above-mentioned CPGs; details of the supporting articles and their levels of evidence; clinical recommendations considering clinical benefits, cost and side effects; and revised recommendations based on customization capability (applicability, acceptability, external validity) were recorded in 4 tables, respectively. Customized recommendations were sent to the faculty members of all universities across the country to score the recommendations from 1 to 9. Results: Agreed recommendations were accepted as the final recommendations while the non-agreed ones were approved after revision. Eventually, 29 customized recommendations under three major categories consisting of screening, diagnosis and treatment of DR were developed along with their sources and levels of evidence. Conclusion: This customized CPGs for management of DR can be used to standardize the referral pathway, diagnosis and treatment of patients with diabetic retinopathy. PMID:27994809

  20. [Incidence and progression of diabetic retinopathy in low income population of Mexico City].

    PubMed

    González-Villalpando, C; González-Villalpando, M E; Rivera Martínez, D; Stern, M P

    1999-01-01

    Diabetic retinopathy is one of the leading causes of preventable blindness in working age population. Diabetes mellitus and this microvascular complication affects frequently Mexican population and presents itself in severe clinical forms. There are no incidence studies of diabetic retinopathy in Mexico. The four year incidence and progression of diabetic retinopathy were investigated in low income diabetic patients of Mexico City. In the follow up phase we studied 164 patients, 76.6% of the patients studied at baseline, 63 were men and 101 women. All participants had a complete ophthalmological exam and seven field stereo photographs. All photographs were graded using internationally accepted criteria in the reading center of our institution. The four year incidence of any level of retinopathy was 22.5%. Worsening of retinopathy occurred in 20.6% and the proliferative diabetic retinopathy stage was reached in 4.5%. Incidence of diabetic retinopathy was associated to age at diagnosis of diabetes mellitus of less than 45 years and progression was associated to duration of disease of more than ten years. The four year incidence of macular edema was 8.8%. These data are important to plan strategies for prevention of blindness and the implementation of optimal care of diabetic patients in our country.

  1. Physical inactivity as a risk factor for diabetic retinopathy? A review.

    PubMed

    Dirani, Mohamed; Crowston, Jonathan G; van Wijngaarden, Peter

    2014-08-01

    Physical inactivity and sedentary behaviour have been identified as modifiable risk factors for diabetes. However, little is known of the associations between physical activity, sedentary behaviour and diabetic retinopathy. The development of diabetic retinopathy is associated with longer duration of diabetes, elevated blood pressure and poor glycaemic control. However these factors only explain a proportion of the risk of retinopathy in individuals with diabetes. Several studies have suggested a protective role for physical activity in diabetic retinopathy. Other work has shown that the time spent watching television is independently associated with abnormal retinal vascular signs. Limitations of the existing studies, such as the absence of objective measures of physical activity, a lack of sedentary behaviour measures, the inclusion of only those with type 1 diabetes and a lack of longitudinal data, make it difficult to draw firm conclusions about the strength of these associations.

  2. Comparisons of serum miRNA expression profiles in patients with diabetic retinopathy and type 2 diabetes mellitus

    PubMed Central

    Ma, Jianping; Wang, Jufang; Liu, Yanfen; Wang, Changyi; Duan, Donghui; Lu, Nanjia; Wang, Kaiyue; Zhang, Lu; Gu, Kaibo; Chen, Sihan; Zhang, Tao; You, Dingyun; Han, Liyuan

    2017-01-01

    OBJECTIVES: The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. METHODS: Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. RESULTS: A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. CONCLUSION: Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings. PMID:28273235

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

    PubMed Central

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

    2012-01-01

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

  4. 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

  5. Role of lipid-lowering agents in the management of diabetic retinopathy

    PubMed Central

    Ioannidou, Estelle; Tseriotis, Vasilis-Spyridon; Tziomalos, Konstantinos

    2017-01-01

    Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus (DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM (T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy. PMID:28138358

  6. The effects of pleiotrophin in proliferative diabetic retinopathy.

    PubMed

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

    2015-01-01

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

  7. Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy

    PubMed Central

    Eshaq, Randa S.; Wright, William S.; Harris, Norman R.

    2014-01-01

    Retinal tissue receives its supply of oxygen from two sources – the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been found to decrease in diabetes, possibly due to either a reduction in neuronal metabolism or to cell death. Diabetes also enhances the rate of conversion of oxygen to superoxide in the retina, with experimental evidence suggesting that mitochondrial superoxide not only drives the overall production of reactive oxygen species, but also initiates several pathways leading to retinopathy, including the increased activity of the polyol and hexosamine pathways, increased production of advanced glycation end products and expression of their receptors, and activation of protein kinase C. PMID:24936440

  8. Neuroendocrine-immune disorder in type 2 diabetic patients with retinopathy.

    PubMed

    Obulkasim, Mutallip; Turdi, Ablikim; Amat, Nurmuhammat; Haxim, Muhtar; Eziz, Rena; Haji, Hurxide; Li, Linlin; Chen, Xueyi; Upur, Halmurat; Ren, Jun

    2011-04-01

    1. Diabetes mellitus is usually accompanied by hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis. Diabetic retinopathy is one of the most devastating complications in diabetes although little is known with regards to the HPA activity in type 2 diabetic patients (T2DM) with diabetic retinopathy. The present study was designed to evaluate the HPA axis activity in type 2 diabetic patients with diabetic retinopathy. 2. Diabetic retinopathy was examined by fluorescein fundus angiography (FFA) in 174 consecutive type 2 diabetic patients. Levels of / were measured using flow cytometry. Serum concentrations of interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), adrenocorticotrophic hormone (ACTH) and cortisone were measured by radioimmunoassay. Plasma levels of monoamines norepinephrine (NE) and dopamine (DA) were assessed using high performance liquid chromatograph equipped with a fluorescence detection. Patients were grouped into the non-diabetic retinopathy (NDR), non-proliferating diabetic retinopathy (NPR) and proliferating diabetic retinopathy (PDR) categories. 3. Patients with PDR showed significantly less than those with NDR and NPR (P<0.05). No significant correlation was found in / and NK or severity of retinopathy among the three patient groups. There was no significant difference in serum IL-1β, IL-6 and TNF-α levels among the different patient groups (P>0.05). The serum concentrations of ACTH and cortisone were lower in PDR patients than other groups. There was no significant difference in plasma concentrations of DA and NE among all three groups (P>0.05). 4. Our data suggest that HPA and immune dysfunction might play a role in the development and/or progression of PDR.

  9. Animal Models of Diabetic Retinopathy: Summary and Comparison

    PubMed Central

    Lo, Amy C. Y.

    2013-01-01

    Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086

  10. Proliferative retinopathy predicts nephropathy: a 25-year follow-up study of type 1 diabetic patients.

    PubMed

    Karlberg, Charlotte; Falk, Christine; Green, Anders; Sjølie, Anne Katrin; Grauslund, Jakob

    2012-08-01

    We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same cohort. All type 1 diabetic patients from Fyn County, Denmark, were identified as of 1 July 1973. One hundred and eighty four patients were examined in 1981-1982 (baseline) and in 2007-2008 (follow-up). The level of retinopathy was graded by ophthalmoscopy at baseline and nine-field digital colour fundus photographs at follow-up. Single spot urine was used to evaluate nephropathy at both examinations. Proliferative retinopathy was present in 29 patients (15.8%) at baseline. At follow-up, these patients were more likely to macroalbuminuria (20.7% vs. 6.5%) than patients without proliferative retinopathy at baseline. In a multivariate logistic regression adjusted for baseline age, sex, duration of diabetes, smoking, HbA(1,) systolic and diastolic blood pressure, odds ratio of nephropathy (micro- and macroalbuminuria combined) was 2.98 (95% confidence interval 1.18-7.51, p = 0.02) for patients with proliferative retinopathy at baseline as compared to those without. At follow-up, there was a close relation between retinopathy and nephropathy. The level of macroalbuminuria was 4.3, 4.6 and 13.0% for patients with no or mild non-proliferative retinopathy, moderate non-proliferative retinopathy and proliferative retinopathy, respectively. In conclusion, proliferative retinopathy is an independent marker of long-term nephropathy in type 1 diabetes. Upcoming studies should examine whether these microvascular complications are also causally linked in type 1 diabetes.

  11. 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.

  12. Risk Factors for Retinopathy and DME in Type 2 Diabetes-Results from the German/Austrian DPV Database.

    PubMed

    Hammes, Hans-Peter; Welp, Reinhard; Kempe, Hans-Peter; Wagner, Christian; Siegel, Erhard; Holl, Reinhard W

    2015-01-01

    To assess the prevalence and risk factors for early and severe diabetic retinopathy and macular edema in a large cohort of patients with type 2 diabetes Retinopathy grading (any retinopathy, severe retinopathy, diabetic macular edema) and risk factors of 64784 were prospectively recorded between January 2000 and March 2013 and analyzed by Kaplan-Meier analysis and logistic regression. Retinopathy was present in 20.12% of subjects, maculopathy was found in 0.77%. HbA1c > 8%, microalbuminuria, hypertension, BMI > 35 kg/m2 and male sex were significantly associated with any retinopathy, while HbA1c and micro- and macroalbuminuria were the strongest risk predictors for severe retinopathy. Presence of macroalbuminuria increased the risk for DME by 177%. Retinopathy remains a significant clinical problem in patients with type 2 diabetes. Metabolic control and blood pressure are relevant factors amenable to treatment. Concomitant kidney disease identifies high risk patients and should be emphasized in interdisciplinary communication.

  13. Association of obesity with diabetic retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS Report no. 8).

    PubMed

    Raman, Rajiv; Rani, Padmaja Kumari; Gnanamoorthy, Perumal; Sudhir, R R; Kumaramanikavel, Govindasamy; Sharma, Tarun

    2010-09-01

    The aim of the study was to report the prevalence of obesity indices in individuals with diabetes and find out their association with diabetic retinopathy in the urban Indian population. Subjects (n = 1,414) were recruited from Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetics Study (SN-DREAMS-I), a cross-sectional study between 2003 and 2006. Anthropometric measurements were carried out, and all patients' fundi were photographed using 45 degrees four-field stereoscopic digital photography. The diagnosis of diabetic retinopathy was based on the modified Klein classification. Generalized obesity and abdominal obesity were defined using WHO Asia Pacific guidelines with the BMI (body mass index) cutoff as > or =23 kg/m(2), WC (waist circumference) cutoffs as > or =90 cm in men and > or =80 cm in women and WHO guidelines using WHR (waist-to-hip ratio) cutoffs as > or =0.90 for men and > or =0.85 for women. Prevalence of obesity defined by BMI and WC was more in women compared to men, and that defined by WHR was more in men compared to women (P < 0.001). The prevalence of isolated generalized obesity, isolated abdominal obesity and combined obesity were 5.4, 10.1 and 58% in men and 4.5, 10.8 and 74.4% in women, respectively. The prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy was more in the isolated abdominal obesity group (26.35 and 6.08%, respectively) than in other subgroups. On logistic regression analysis, isolated abdominal obesity (OR 2.02, 95% CI: 1.06-3.86) and increased WHR in women (OR 1.48 95% CI: 1.10-2.38) were associated with diabetic retinopathy; BMI > or = 23 (OR 0.66, 95% CI: 0.48-0.90) and combined obesity (OR 0.72, 95% CI: 0.53-0.99) had a protective role for any diabetic retinopathy in the overall group. In the urban south Indian population, isolated abdominal obesity and higher WHR in women were associated with diabetic retinopathy, but not with the severity of diabetic retinopathy.

  14. [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.

  15. Diabetic retinopathy, duration of diabetes and risk factors of atherosclerotic cardiovascular disease.

    PubMed

    Job, D; Eschwège, E; Tchobroutsky, G; Guyot-Argenton, C; Aubry, J P; Dérot, N

    1975-01-01

    The present study, concerning 145 insulin-dependent diabetics showed positive relationships between the severity of retinal disease on the one hand, and body weight, blood pressure, and serum cholesterol level on the other. These relationships remain significant when the duration of the clinical diabetes and the age of the patient are taken into account. Two interpretations are suggested. They are not incompatible. In diabetic subjects, either the increase in blood pressure and serum cholesterol level causes an aggravation of diabetic retinopathy or there exists a common factor at the origin of retinal lesions and of an increase in risk of cardiovascular disease through atherosclerosis.

  16. 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

  17. 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

  18. Predominant cone photoreceptor dysfunction in a hyperglycaemic model of non-proliferative diabetic retinopathy.

    PubMed

    Alvarez, Yolanda; Chen, Kenneth; Reynolds, Alison L; Waghorne, Nora; O'Connor, John J; Kennedy, Breandán N

    2010-01-01

    Approximately 2.5 million people worldwide are clinically blind because of diabetic retinopathy. In the non-proliferative stage, the pathophysiology of this ocular manifestation of diabetes presents as morphological and functional disruption of the retinal vasculature, and dysfunction of retinal neurons. However, it is uncertain whether the vascular and neuronal changes are interdependent or independent events. In addition, the identity of the retinal neurons that are most susceptible to the hyperglycaemia associated with diabetes is unclear. Here, we characterise a novel model of non-proliferative diabetic retinopathy in adult zebrafish, in which the zebrafish were subjected to oscillating hyperglycaemia for 30 days. Visual function is diminished in hyperglycaemic fish. Significantly, hyperglycaemia disrupts cone photoreceptor neurons the most, as evidenced by prominent morphological degeneration and dysfunctional cone-mediated electroretinograms. Disturbances in the morphological integrity of the blood-retinal barrier were also evident. However, we demonstrate that these early vascular changes are not sufficient to induce cone photoreceptor dysfunction, suggesting that the vascular and neuronal complications in diabetic retinopathy can arise independently. Current treatments for diabetic retinopathy target the vascular complications. Our data suggest that cone photoreceptor dysfunction is a clinical hallmark of diabetic retinopathy and that the debilitating blindness associated with diabetic retinopathy may be halted by neuroprotection of cones.

  19. Erythrocyte aldose reductase activity and sorbitol levels in diabetic retinopathy

    PubMed Central

    Satyanarayana, A.; Balakrishna, N.; Ayyagari, Radha; Padma, M.; Viswanath, K.; Petrash, J. Mark

    2008-01-01

    Purpose Activation of polyol pathway due to increased aldose reductase (ALR2) activity has been implicated in the development of diabetic complications including diabetic retinopathy (DR), a leading cause of blindness. However, the relationship between hyperglycemia-induced activation of polyol pathway in retina and DR is still uncertain. We investigated the relationship between ALR2 levels and human DR by measuring ALR2 activity and its product, sorbitol, in erythrocytes. Methods We enrolled 362 type 2 diabetic subjects (T2D) with and without DR and 66 normal subjects in this clinical case-control study. Clinical evaluation of DR in T2D patients was done by fundus examination. ALR2 activity and sorbitol levels along with glucose and glycosylated hemoglobin (HbA1C) levels in erythrocytes were determined. Results T2D patients with DR showed significantly higher specific activity of ALR2 as compared to T2D patients without DR. Elevated levels of sorbitol in T2D patients with DR, as compared to T2D patients without DR, corroborated the increased ALR2 activity in erythrocytes of DR patients. However, the increased ALR2 activity was not significantly associated with diabetes duration, age, and HbA1C in both the DR group and total T2D subjects. Conclusions Levels of ALR2 activity as well as sorbitol in erythrocytes may have value as a quantitative trait to be included among other markers to establish a risk profile for development of DR. PMID:18385795

  20. Spectrally optimal illuminations for diabetic retinopathy detection in retinal imaging

    NASA Astrophysics Data System (ADS)

    Bartczak, Piotr; Fält, Pauli; Penttinen, Niko; Ylitepsa, Pasi; Laaksonen, Lauri; Lensu, Lasse; Hauta-Kasari, Markku; Uusitalo, Hannu

    2017-01-01

    Retinal photography is a standard method for recording retinal diseases for subsequent analysis and diagnosis. However, the currently used white light or red-free retinal imaging does not necessarily provide the best possible visibility of different types of retinal lesions, important when developing diagnostic tools for handheld devices, such as smartphones. Using specifically designed illumination, the visibility and contrast of retinal lesions could be improved. In this study, spectrally optimal illuminations for diabetic retinopathy lesion visualization are implemented using a spectrally tunable light source based on digital micromirror device. The applicability of this method was tested in vivo by taking retinal monochrome images from the eyes of five diabetic volunteers and two non-diabetic control subjects. For comparison to existing methods, we evaluated the contrast of retinal images taken with our method and red-free illumination. The preliminary results show that the use of optimal illuminations improved the contrast of diabetic lesions in retinal images by 30-70%, compared to the traditional red-free illumination imaging.

  1. Pupillary responses in non-proliferative diabetic retinopathy

    PubMed Central

    Park, Jason C.; Chen, Yi-Fan; Blair, Norman P.; Chau, Felix Y.; Lim, Jennifer I.; Leiderman, Yannek I.; Shahidi, Mahnaz; McAnany, J. Jason

    2017-01-01

    The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities. PMID:28332564

  2. Diabetic Retinopathy in Italy: Epidemiology Data and Telemedicine Screening Programs

    PubMed Central

    Midena, Edoardo

    2016-01-01

    In Italy, the number of people living with diabetes is about 3.5 million (5.5% of the population), with an increase by about 60% in the last 20 years and with 1 person out of 3 older than 65 years. The Italian Health Service system estimates that 10 billion euros is spent annually on caring for patients with diabetes, a figure that increases yearly. No national data on prevalence and incidence of legal blindness in patients with diabetes and no national registry of patients with diabetic retinopathy (DR) are currently available. However, the available epidemiological data (in several locations throughout the country) are consistent with those reported in other European countries. The use of telemedicine for the screening of DR in Italy is confined to geographically limited locations. The available data in the literature on implementation and use of telematic screening proved to be successful from patient, caregiver, and authorities point of view. This review addresses the available epidemiological data on DR and telematic screening realities in Italy and thus may help in establishing a national screening program. PMID:27990441

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

    PubMed

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

    2012-07-01

    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.

  4. 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

  5. Prevalence and factors associated with diabetic retinopathy among diabetic patients at Arbaminch General Hospital, Ethiopia: Cross sectional study

    PubMed Central

    Chisha, Yilma; Terefe, Wondwossen; Assefa, Huruy; Lakew, Serawit

    2017-01-01

    Background Currently 93 million people are estimated as living with diabetic retinopathy worldwide. The prevalence and risk factors of diabetic retinopathy in developed countries have been well documented; but in Ethiopia, data on prevalence and associated factors of diabetic retinopathy is lacking. Objective To determine prevalence and factors associated with development of diabetic retinopathy among diabetic patients at Arbaminch General Hospital, Ethiopia. Method Cross-sectional study design with record review of 400 diabetic patients was conducted at Arbaminch General Hospital from November to January 2015. Among 400 diabetic patients, 270 patients with baseline information and without history of hypertension at baseline were included in this study. But patients with gestational diabetes and with retinopathy at baseline were excluded from the study. Consecutive sampling technique was applied to select study participants. Data of cohorts was extracted from medical record using pre tested structured extraction check list. Data cleaning, coding, categorizing, merging and analysis carried out by STATA version 12. Descriptive statistics was done and presented accordingly. Bivariate binary logistic regression analysis was done to select potential candidates for the full model at P-value cutoff point ≤ 0.25 and multivariable binary logistic regression analysis was made to estimate the independent effect of predictors on the occurrence of diabetic retinopathy. Model diagnostic tests were done, final model fitness was checked using Hosmer and Lemeshow chi square test. Finally, statistical significance was tested at P-value <0.05. Result Prevalence of diabetic retinopathy among diabetic patients at Arbaminch General Hospital was 13%. Adjusted analysis showed that the odds of diabetic retinopathy were statistically and significantly associated with baseline age (AOR = 6.06: 95%CI; 2.42, 15.21), baseline systolic blood pressure level (AOR = 4.38: 95%CI; 1.64, 11

  6. Automated microaneurysm detection in diabetic retinopathy using curvelet transform

    NASA Astrophysics Data System (ADS)

    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.

  7. Ocular and cardiovascular autonomic function in diabetic patients with varying severity of retinopathy.

    PubMed

    Datta, Shivaji; Biswas, N R; Saxena, Rohit; Deepak, K K; Menon, Vimla; Garg, S P; Tandon, Radhika

    2005-04-01

    The study was conducted to assess the ocular and cardiovascular autonomic function in diabetic patients with varying severity of diabetic retinopathy. Ocular and cardiovascular autonomic function tests were performed in 30 patients with type 2 Diabetes Mellitus (10 in each group of proliferative retinopathy, non-proliferative retinopathy and no retinopathy) of more than 5 years duration and 10 normal controls. Ocular autonomic function tests were done by measuring pupil cycle time and denervation hypersensitivity with 0.125% pilocarpine and 0.5% phenylephrine. Cardiovascular autonomic function was measured by a battery of standard tests. Denervation hypersensitivity to 0.125% pilocarpine and to 0.5% phenylephrine and pupil cycle time showed statistically significant differences (P value < 0.001) between controls and patients with proliferative retinopathy (PDR) and also between no retinopathy and PDR (P < 0.001). Systemic autonomic function tests namely expiration--inspiration ratio, difference in heart rate, 30th beat and 15th beat ratio in head up tilt and difference in diastolic blood pressure in head up tilt test also showed significant difference (P < 0.01) between controls and all 3 groups of diabetics. There was statistically significant difference found in para-sympathetic ocular autonomic dysfunction between NPDR and controls. Ocular and systemic autonomic dysfunctions are related to the severity of diabetic retinopathy.

  8. 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.

  9. [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.

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

    PubMed Central

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

    2015-01-01

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

  11. Neovascular glaucoma after vitrectomy in patients with proliferative diabetic retinopathy

    PubMed Central

    Kwon, Jin-woo; Jee, Donghyun; La, Tae Yoon

    2017-01-01

    Abstract To evaluate the prevalence and risk factors of neovascular glaucoma (NVG) after vitrectomy in patients with vitreous hemorrhage associated with proliferative diabetic retinopathy (PDR). This retrospective, noncomparative, observational study included 127 eyes of 127 patients with PDR who received vitrectomy with a follow-up period of at least 6 months. The prevalence of NVG and associated risk factors were assessed including sex, age, previous panretinal photocoagulation, baseline intraocular pressure, combined phacovitrectomy, and pretreatment with intravitreal bevacizumab (IVB) before vitrectomy for the treatment of vitreous hemorrhage. NVG developed in 15 (11.8%) of 127 patients. Of the 15 eyes with NVG, 11 cases (73.3%) postoperatively developed NVG within 6 months. Postoperative NVG was associated with preoperative IVB treatment (odds ratio, 4.43; P = 0.019). The prevalence of NVG after vitrectomy was 11.8%, and an associated risk factor for NVG was preoperative IVB for the treatment of vitreous hemorrhage. PMID:28272234

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

    PubMed Central

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

    2015-01-01

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

  13. 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

  14. Peripapillary Retinal Nerve Fiber Layer Changes in Preclinical Diabetic Retinopathy: A Meta-Analysis

    PubMed Central

    Chen, Xiaofei; Nie, Chuang; Gong, Yan; Zhang, Ying; Jin, Xin; Wei, Shihui; Zhang, Maonian

    2015-01-01

    Background Diabetic retinopathy is a microvascular neurodegenerative disorder in diabetic patients. Peripapillary retinal nerve fiber layer changes have been described in patients with preclinical diabetic retinopathy, but study results have been inconsistent. Objective To assess changes in peripapillary retinal nerve fiber layer thickness in diabetic patients with preclinical diabetic retinopathy. Methods A literature search was conducted through PubMed, EMBASE, Web of Science and Cochrane Library. Case-control studies on RNFL thickness in preclinical diabetic retinopathy patients and healthy controls were retrieved. A meta-analysis of weighted mean difference and a sensitivity analysis were performed using RevMan 5.2 software. Results Thirteen case-control studies containing 668 diabetic patients and 556 healthy controls were selected. Peripapillary RNFL thickness was significantly reduced in patients with preclinical diabetic retinopathy compared to healthy controls in studies applying Optical Coherence Tomography (-2.88μm, 95%CI: -4.44 to -1.32, P = 0.0003) and in studies applying Scanning Laser Polarimeter (-4.21μm, 95%CI: -6.45 to -1.97, P = 0.0002). Reduction of RNFL thickness was significant in the superior quadrant (-3.79μm, 95%CI: -7.08 to -0.50, P = 0.02), the inferior quadrant (-2.99μm, 95%CI: -5.44 to -0.54, P = 0.02) and the nasal quadrant (-2.88μm, 95%CI: -4.93 to -0.82, P = 0.006), but was not significant in the temporal quadrant (-1.22μm, 95%CI: -3.21 to 0.76, P = 0.23), in diabetic patients. Conclusion Peripapillary RNFL thickness was significantly decreased in preclinical diabetic retinopathy patients compared to healthy control. Neurodegenerative changes due to preclinical diabetic retinopathy need more attention. PMID:25965421

  15. Diabetic Retinopathy Screening Using Telemedicine Tools: Pilot Study in Hungary

    PubMed Central

    Eszes, Dóra J.; Szabó, Dóra J.; Russell, Greg; Kirby, Phil; Paulik, Edit; Nagymajtényi, László

    2016-01-01

    Introduction. Diabetic retinopathy (DR) is a sight-threatening complication of diabetes. Telemedicine tools can prevent blindness. We aimed to investigate the patients' satisfaction when using such tools (fundus camera examination) and the effect of demographic and socioeconomic factors on participation in screening. Methods. Pilot study involving fundus camera screening and self-administered questionnaire on participants' experience during fundus examination (comfort, reliability, and future interest in participation), as well as demographic and socioeconomic factors was performed on 89 patients with known diabetes in Csongrád County, a southeastern region of Hungary. Results. Thirty percent of the patients had never participated in any ophthalmological screening, while 25.7% had DR of some grade based upon a standard fundus camera examination and UK-based DR grading protocol (Spectra™ software). Large majority of the patients were satisfied with the screening and found it reliable and acceptable to undertake examination under pupil dilation; 67.3% were willing to undergo nonmydriatic fundus camera examination again. There was a statistically significant relationship between economic activity, education and marital status, and future interest in participation. Discussion. Participants found digital retinal screening to be reliable and satisfactory. Telemedicine can be a strong tool, supporting eye care professionals and allowing for faster and more comfortable DR screening. PMID:28078306

  16. 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

  17. Automated detection of diabetic retinopathy: barriers to translation into clinical practice

    PubMed Central

    Abramoff, Michael D; Niemeijer, Meindert; Russell, Stephen R

    2010-01-01

    Automated identification of diabetic retinopathy (DR), the primary cause of blindness and visual loss for those aged 18–65 years, from color images of the retina has enormous potential to increase the quality, cost–effectiveness and accessibility of preventative care for people with diabetes. Through advanced image analysis techniques, retinal images are analyzed for abnormalities that define and correlate with the severity of DR. Translating automated DR detection into clinical practice will require surmounting scientific and nonscientific barriers. Scientific concerns, such as DR detection limits compared with human experts, can be studied and measured. Ethical, legal and political issues can be addressed, but are difficult or impossible to measure. The primary objective of this review is to survey the methods, potential benefits and limitations of automated detection in order to better manage translation into clinical practice, based on extensive experience with the systems we have developed. PMID:20214432

  18. The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy

    PubMed Central

    Dietrich, Nadine; Kolibabka, Matthias; Busch, Stephanie; Bugert, Petra; Kaiser, Ulrike; Lin, Jihong; Fleming, Thomas; Morcos, Michael; Klein, Thomas; Schlotterer, Andrea; Hammes, Hans-Peter

    2016-01-01

    Background/aims Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. Methods Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1.1 (immunohistochemistry), nuclei in the ganglion cell layer, GFAP (western blot), and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR) were determined. In C. elegans, neuronal function was determined using worm tracking software. Results Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency) was significantly prevented in C. elegans. Conclusion Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit. PMID:27942008

  19. Novel vitreous modulators for pharmacologic vitreolysis in the treatment of diabetic retinopathy.

    PubMed

    Costa, Elaine de Paula Fiod; Rodrigues, Eduardo B; Farah, Michel E; Sebag, Jerry; Meyer, Carsten H

    2011-03-01

    Vitreous constitutes about 80% of the volume of the human eye. It is an extended extracellular matrix that is composed of collagen, hyaluronan, and other extracellular matrix molecules, but mostly water. In both health as well as disease, especially diabetic retinopathy (DR), special attention should be drawn to the posterior vitreous cortex and its relation to the retinal surface. The important role of vitreous in the pathogenesis of proliferative DR has already been demonstrated by several experimental and clinical studies. Thus, vitreo-retinal separation by pharmacologic vitreolysis and/or removal by surgical means are appropriate approaches to interrupt the pathogenic contribution of vitreous and prevent progression of diabetic retinopathy to more advanced stages. This review describes various aspects of the molecular morphology and structural anatomy of vitreous and the vitreo-retinal interface, as well as the role of vitreous in the pathophysiology of DR. Lastly, this treatise provides a critical analysis of novel vitreous modulators for pharmacologic vitreolysis in the treatment of DR. Microplasmin is currently the most promising approach to treat vitreoretinal traction by pharmacologic vitreolysis.

  20. [Trial treatment of diabetic retinopathy by inhibition of pituitary somatotropin secretion with MAP].

    PubMed

    Bruni, B; Bruni-Bocher, K; Della Valle, A; Gamba, S

    1975-03-21

    The recent literature relating to the pathogenesis of diabetic retinopathy, with or without nephropaty, is critically reviewed. Particular attention is given to the Growth Hormone (GH) hypothesis. The various procedures of hypophysectomy are discussed, including the possible ways of suppressing growth hormone production or overproduction by drugs, and expecially by medroxyprogesterone acetate (MAP). Personal results obtained with long-term administration of MAP in deposit form on alternate days in 10 patients with advanced retinopathy are described. An icostant and rely significant suppression of the GH response to insulin-induced hypoglicemia was noted in 6 cases, showing that a complete pituitary inactivation had been achieved. Therefore, the modifications observed in the fundus picture (studied with retinal photographs according to the Hammersmith Hospital Standards) seem to have no relationship with such a condition. The features involved were Microaneurysms and Haemorrhages (HAEMS) and Exudates (EX);New Vessels (NV) and Retinitis Proliferans (RP) were unaffected. Subjective improvement is visual acuity appeared to be more frequent, with various possible explanations. MAP was without appreciable effect on the clinical and metabolic course of the diabetes, or on renal function in cases of concomitant nephropathy. In the light of these preliminary results, further investigations might seem to be justified.

  1. Multiple factors in the prediction of risk of proliferative diabetic retinopathy.

    PubMed

    Rand, L I; Krolewski, A S; Aiello, L M; Warram, J H; Baker, R S; Maki, T

    1985-12-05

    To identify risk factors for the development of proliferative diabetic retinopathy, we compared 111 patients with longstanding insulin-dependent diabetes who had proliferative retinopathy (cases) with 81 patients with diabetes of similar duration (an average of 26 years) who did not have proliferative diabetic retinopathy (controls). The cases had diabetes that was more difficult to manage, as evidenced by their more frequent blood sugar levels above 200 mg per deciliter (11 mmol per liter) on routine clinic visits (odds ratio, 1.6 for each increment of 10 per cent in the relative frequency), and they expended less effort in managing their diabetes, as indicated by their less frequent testing of urine for sugar (odds ratio, 0.3). Among those who did not have myopia, the cases also had an excess of the HLA-DR phenotypes 4/0, 3/0, or X/X (odds ratio, 10.0). Among those with myopia, these phenotypes did not carry an increased risk of proliferative retinopathy. These results support a multifactorial model for the development of proliferative diabetic retinopathy; however, the mechanisms of action of the identified factors remain unknown.

  2. Urinary 6-sulfatoxymelatonin level in diabetic retinopathy patients with type 2 diabetes.

    PubMed

    Chen, Wei; Cao, Hui; Lu, Qian-Yi; Wang, Na; Zhao, Shu-Zhi; Xu, Xun; Zheng, Zhi

    2014-01-01

    Melatonin is a powerful antioxidant. Decreased melatonin excretion has been reported to be associated with several oxidative stress-related diseases. The urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), has proved to be a very reliable index of melatonin production. The present study aims to evaluate the level of urinary aMT6s in patients with type 2 diabetes mellitus and diabetic retinopathy. Urine samples were collected from 10 patients with diabetes and no diabetic retinopathy (NDR), 19 patients with nonproliferative diabetic retinopathy (NPDR), 38 patients with proliferative diabetic retinopathy (PDR), and 16 subjects without diabetes mellitus, who served as controls. The level of aMT6s in specimens was assayed by a commercial aMT6s ELISA kit, creatinine levels were also measured for each sample to get urinary aMT6s/creatinine ratio. Creatinine-adjusted urinary aMT6s values were compared among four groups. The urinary aMT6s (mean ± SD) levels were 9.95 ± 2.42, 9.90 ± 2.28, 8.40 ± 1.84 and 5.58 ± 1.33 ng/mg creatinine in the controls and in patients with NDR, NPDR, or PDR, respectively. The urinary aMT6s level of the PDR group was significantly lower than that of the control, NDR and DR groups. No significant difference was found among the control, NDR and DR groups. After adjustment for various factors (age, smoking, cancer, and coronary heart disease) that may influence the aMT6s level, the odds-ratio of urinary aMT6s comparing PDR patients to controls was 0.246 (95% confidence interval = 0.108-0.558, P = 0.001). Therefore, the urinary aMT6s level is significantly decreased in diabetic patients with PDR but not in diabetic patients without PDR, which indicates that decreased urinary aMT6s level may be associated with the pathogenesis of PDR.

  3. [Present state of diagnostic and screening of the diabetic retinopathy and diabetic macular oedema].

    PubMed

    Kalvodová, B

    2013-03-01

    Diabetic retinopathy (DR) and its complications are worldwide one ofthe main causes ofthe visual impairment and blindness. An incidence of DR is substantially raised due to increasing amount of diabetic patients in population. Systematic screening of diabetic eye complications makes possible a timely incorporation of patients with diabetes mellitus to a lifelong preventive ophthalmological treatment. According to an extent of progress of the DR, these patients are treated by retinal laser coagulation or inhibitors of growth factors and/or surgical treatment of retinal complications by the pars plana vitrectomy. Essential aspects of the effective prevention of the origin and development of diabetic eye complications are cooperation of diabetologist and ophthalmologist, education of patients and their active approach to the treatment.

  4. 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

  5. Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy

    PubMed Central

    Srivastav, Khushboo; Mahdi, Abbas A.; Shukla, Rajendra K.; Meyer, Carsten H.; Akduman, Levent; Khanna, Vinay K.

    2016-01-01

    Purpose To study the correlation between serum levels of vitamin B12, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT). Methods In a tertiary care center–based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40–65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B12 and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables. Results Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B12 and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001). Conclusions This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy. PMID:27994434

  6. Automatic screening and classification of diabetic retinopathy and maculopathy using fuzzy image processing.

    PubMed

    Rahim, Sarni Suhaila; Palade, Vasile; Shuttleworth, James; Jayne, Chrisina

    2016-12-01

    Digital retinal imaging is a challenging screening method for which effective, robust and cost-effective approaches are still to be developed. Regular screening for diabetic retinopathy and diabetic maculopathy diseases is necessary in order to identify the group at risk of visual impairment. This paper presents a novel automatic detection of diabetic retinopathy and maculopathy in eye fundus images by employing fuzzy image processing techniques. The paper first introduces the existing systems for diabetic retinopathy screening, with an emphasis on the maculopathy detection methods. The proposed medical decision support system consists of four parts, namely: image acquisition, image preprocessing including four retinal structures localisation, feature extraction and the classification of diabetic retinopathy and maculopathy. A combination of fuzzy image processing techniques, the Circular Hough Transform and several feature extraction methods are implemented in the proposed system. The paper also presents a novel technique for the macula region localisation in order to detect the maculopathy. In addition to the proposed detection system, the paper highlights a novel online dataset and it presents the dataset collection, the expert diagnosis process and the advantages of our online database compared to other public eye fundus image databases for diabetic retinopathy purposes.

  7. Longitudinal Commercial Claims–Based Cost Analysis of Diabetic Retinopathy Screening Patterns

    PubMed Central

    Fitch, Kathryn; Weisman, Thomas; Engel, Tyler; Turpcu, Adam; Blumen, Helen; Rajput, Yamina; Dave, Purav

    2015-01-01

    Background Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service. Objective To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes. Methods Truven Health MarketScan commercial databases (2000–2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001–2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001–2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1–4, 5–7, and 8–10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables. Results In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts’ mean incremental cost increase was $185 between the 0- and 1–4–year cohorts (P <.003) and $202 between the 0- and 5–7–year cohorts (P <.023). The

  8. 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

  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.

  11. 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

  12. 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 ...

  13. Intravitreal bevacizumab for persistent macular edema with proliferative diabetic retinopathy.

    PubMed

    Gulkilik, Gokhan; Taskapili, Muhittin; Kocabora, Selim; Muftuoglu, Gulipek; Demirci, Goktug

    2010-12-01

    To evaluate the effectiveness of an intravitreal bevacizumab injection on retinal neovascularization and diabetic macular edema (DME) refractory to laser photocoagulation therapy. Thirty-four eyes of 22 patients with proliferative diabetic retinopathy and DME refractory to laser photocoagulation therapy received an intravitreal injection of 1.25 mg/0.05 ml of bevazicumab. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), regression of neovascularization over time, and correlation between BCVA and CMT were evaluated. Follow-up visits were at weeks 1, 2 and 4 and months 3 and 6. Mean BCVA was significantly better than baseline only at week 2 (P = 0.036). Mean CMT decreased significantly from baseline at weeks 1, 2, and 4 (P = 0.001). At months 3 and 6, mean CMT increased, albeit insignificantly (P = 0.804 and P = 1.0). The decrease in fluorescein leakage was moderate in all eyes at the end of week 1. At week 2, there was total resolution of fluorescein leakage in 24 (70.5%) eyes and moderate resolution in 10 (29.5%) eyes. At the end of month 3, the fluorescein leakage was fully resolved in 5 (14.7%) eyes, moderately resolved in 24 (70.5%) eyes, and was similar to baseline in 5 (14.7%) eyes. At month 6, the fluorescein leakage was fully resolved in 3 (8.8%) eyes, moderately resolved in 20 (58.8%) eyes, and was similar to baseline in 11 (32.4%) eyes. A moderate but insignificant negative correlation was found between visual acuity and CMT (P > 0.05). Persistence or recurrence of neovascular tissue after panretinal photocoagulation may be attributed to the production of vascular endothelial growth factor by the residual ischemic retina, which also results in persistent or recurrent DME despite macular grid photocoagulation.

  14. 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

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

    PubMed

    Das, Undurti N

    2016-10-01

    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.

  16. Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England

    PubMed Central

    Jones, Colin D.; Greenwood, Richard H.; Misra, Aseema; Bachmann, Max O.

    2012-01-01

    OBJECTIVE To estimate the incidence of diabetic retinopathy in relation to retinopathy grade at first examination and other prognostic characteristics. RESEARCH DESIGN AND METHODS This was a dynamic cohort study of 20,686 people with type 2 diabetes who had annual retinal photography up to 14 times between 1990 and 2006. Cumulative and annual incidence rates were estimated using life tables, and risk factors for progression were identified using Cox regression analysis. RESULTS Of 20,686 patients without proliferative diabetic retinopathy (PDR) or sight-threatening maculopathy at their first retinal examination (baseline), 16,444 (79%) did not have retinopathy, 3,632 (18%) had nonproliferative retinopathy, and 610 (2.9%) had preproliferative retinopathy. After 5 years, few patients without retinopathy at baseline developed preproliferative retinopathy (cumulative incidence 4.0%), sight-threatening maculopathy (0.59%), or PDR (0.68%); after 10 years, the respective cumulative incidences were 16.4, 1.2, and 1.5%. Among those with nonproliferative (background) retinopathy at baseline, after 1 year 23% developed preproliferative retinopathy, 5.2% developed maculopathy, and 6.1% developed PDR; after 10 years, the respective cumulative incidences were 53, 9.6, and 11%. Patients with nonproliferative retinopathy at baseline were five times more likely to develop preproliferative, PDR, or maculopathy than those without retinopathy at baseline (adjusted hazard ratio 5.0 [95% CI 4.4–5.6]). CONCLUSIONS Few patients without diabetic retinopathy at the initial screening examination developed preproliferative retinopathy, PDR, or sight-threatening maculopathy after 5–10 years of follow-up. Screening intervals longer than a year may be appropriate for such patients. PMID:22279031

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

    PubMed

    Murthy, G V S; Das, Taraprasad

    2016-01-01

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

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

    PubMed Central

    Murthy, GVS; Das, Taraprasad

    2016-01-01

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

  19. Elevation of serum apelin-13 associated with proliferative diabetic retinopathy in type 2 diabetic patients

    PubMed Central

    Du, Jun-Hui; Li, Xia; Li, Rong; Xu, Lin; Ma, Ran-Ran; Liu, Song-Fang; Zhang, Zhong; Sun, Hong-Zhi

    2014-01-01

    AIM To compare apelin-13, a ligand of G-protein-coupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor (VEGF) serum levels in type 2 diabetes mellitus (T2DM) with or without retinopathy, and to investigate the relationship between the serum concentration of apelin-13 and diabetes retinopathy. METHODS Sixty-nine patients with T2DM were enrolled. Of the 69 patients, 16 had proliferative diabetic retinopathy (PDR group), 23 had non-PDR (NPDR group) and 30 had no retinopathy (T2DM group). Subjects' information, including demographics, medical history, and use of medications were recorded. Their serum samples were collected for measuring the levels of C-reactive protein (CRP), serum lipid and glycosylated hemoglobin. Apelin-13 and VEGF serum levels were measured by enzyme-linked immunosorbent assay. Kruskal-Wallis test and one-way ANOVA were used to compare the differences among these groups. Chi-square test was used to assess categorical variables. Correlations between variables were investigated by Spearman rho correlation test and stepwise regression analysis. All statistical analyses were performed through SPSS 17.0 software. RESULTS Sex, age, body mass index (BMI), blood pressure, CRP, hemoglobin A1c (HbA1c) have no significantly difference in the three groups. Serum level of apelin-13 was significantly elevated in PDR group as compared with T2DM group (P=0.041). Differences of VEGF serum concentration in the three groups were statistically significant (P=0.007, P=0.007 and P<0.001, respectively). Spearman rho correlation test showed that serum apelin-13 was positively correlated with BMI, serum triglycerides, VEGF, but not with age, duration of diabetes, blood pressure, CRP, HbA1c and total-cholesterol. Stepwise regression analysis showed that BMI also significantly associated with serum apelin-13 (P=0.002), while VEGF and serum triglycerides were irrelevant. CONCLUSION This study elucidated a positive

  20. The Association between Vitamin D Deficiency and Diabetic Retinopathy in Type 2 Diabetes: A Meta-Analysis of Observational Studies

    PubMed Central

    Luo, Bang-An; Gao, Fan; Qin, Lu-Lu

    2017-01-01

    Emerging evidence from in vivo and in vitro studies have shown that vitamin D may play an important role in the development of diabetic retinopathy (DR), but individually published studies showed inconclusive results. The aim of this study was to quantitatively summarize the association between vitamin D and the risk of diabetic retinopathy. We conducted a systematic literature search of Pubmed, Medline, and EMBASE updated in September 2016 with the following keywords: “vitamin D” or “cholecalciferol” or “25-hydroxyvitamin D” or “25(OH)D” in combination with “diabetic retinopathy” or “DR”. Fifteen observational studies involving 17,664 subjects were included. In this meta-analysis, type 2 diabetes patients with vitamin D deficiency (serum 25(OH)D levels <20 ng/mL) experienced a significantly increased risk of DR (odds ratio (OR) = 2.03, 95% confidence intervals (CI): 1.07, 3.86), and an obvious decrease of 1.7 ng/mL (95% CI: −2.72, −0.66) in serum vitamin D was demonstrated in the patients with diabetic retinopathy. Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect. In conclusion, the evidence from this meta-analysis indicates an association between vitamin D deficiency and an increased risk of diabetic retinopathy in type 2 diabetes patients. PMID:28335514

  1. [Effects of complex therapy with emoxipin on the course of diabetic retinopathy].

    PubMed

    Kozlov, S A; Khyshiktuev, B S; Logunov, N A

    2003-01-01

    The efficacy of 1% emoxipin solution (eye drops) in the nonproliferative stage of diabetic retinopathy was studied. The inhibition of lipid peroxidation and an enhancement of antioxidizing guard were observed both after the therapy by the above preparation and 3 months later. It was concluded that emoxipin was effective for leveling the biochemical violations in the "lipid peroxidation--antioxidants" system of lachrymal fluid in patients with the nonproliferative stage of diabetic retinopathy. The prescription of emoxipin eye drops can enhance the efficacy of therapy at the early stages of the disease.

  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. Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

    PubMed Central

    2014-01-01

    Purpose Increased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for ‘Diabetes Vision Function’, on diabetic retinopathy. Methods Streptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at ~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1β and NF-kB. Results Diabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3–4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1β and NF-kB levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities. Conclusions Nutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow

  4. Advanced Glycation End Products and Diabetic Complications

    PubMed Central

    Singh, Varun Parkash; Bali, Anjana; Singh, Nirmal

    2014-01-01

    During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed. PMID:24634591

  5. 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.

  6. 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).

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

    PubMed Central

    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

    2016-01-01

    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)-Leprdb/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. 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

  9. 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…

  10. 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.

  11. Assessment of the Relationship between Diabetic Retinopathy and Nailfold Capillaries in Type 2 Diabetics with a Noninvasive Method: Nailfold Videocapillaroscopy

    PubMed Central

    Balkarlı, Ayşe; Yeşil, Bayram; Tokuç, Abdullah; Durmaz, Doğan; Görar, Süheyla; Çekin, Ayhan Hilmi

    2016-01-01

    Background and Objectives. Nailfold capillaroscopy is an easy and noninvasive technique used to investigate dermal microvasculature. Traditional investigations of vascularity do not detect changes until they are well-established in type 2 diabetics. The objective of the current study was to evaluate nailfold capillaries in type 2 diabetes mellitus patients and to determine the association of retinopathy with changes in the nailfold capillaries. Materials and Methods. Capillaroscopic findings by nailfold capillaroscopy and fundoscopic examinations were assessed in 216 patients with type 2 diabetes mellitus and 101 healthy controls included in this prospective study. Results. Retinopathy was detected in 43.05% of diabetic patients (n = 93). Capillaroscopic findings including tortuosity (p < 0.001), bushy capillary (p < 0.001), neoformation (p < 0.001), bizarre capillary (p < 0.001), microhemorrhage (p = 0.001), capillary ectasia (p = 0.002), and aneurysm (p = 0.004) were significantly higher in diabetic group than control group. In logistic regression analysis, only tortuosity was shown significant (OR, 2.16; p = 0.036). There was also a significant relation between diabetes duration and most of the capillaroscopic findings. Conclusion. Capillaroscopic changes were found to be correlated with diabetic retinopathy, in particular with longer disease duration in our study. Capillaroscopic imaging could be a useful new technique for assessment of diabetic microvascular changes. PMID:28058264

  12. Diabetes Onset at 31–45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes

    PubMed Central

    Zou, Wenjun; Ni, Lisha; Lu, Qianyi; Zou, Chen; Zhao, Minjie; Xu, Xun; Chen, Haibing; Zheng, Zhi

    2016-01-01

    This hospital-based, cross-sectional study investigated the effect of age of diabetes onset on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. A total of 5,214 patients with type 2 DM who were referred to the Department of Ophthalmology at the Shanghai First People’s Hospital from 2009 to 2013 was eligible for inclusion. Diabetic retinopathy status was classified using the grading system of the Early Treatment Diabetic Retinopathy Study (ETDRS). Logistic and hierarchical regression analyses were used to identify independent variables affecting the development of DR. Upon multiple logistic regression analysis, patient age at the time of diabetes onset was significantly associated with development of DR. Further, when the risk of retinopathy was stratified by patient age at the onset of diabetes, the risk was highest in patients in whom diabetes developed at an age of 31–45 years (odds ratio [OR] 1.815 [1.139–2.892]; p = 0.012). Furthermore, when patients were divided into four groups based on the duration of diabetes, DR development was maximal at a diabetes onset age of 31–45 years within each group. A diabetes onset age of 31–45 years is an independent risk factor for DR development in Chinese type 2 DM patients. PMID:27897261

  13. Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

    PubMed Central

    Gonzalez-Salinas, Roberto; Garcia-Gutierrez, Maria C; Garcia-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul; Soberon-Ventura, Vidal R; Gonzalez, Victoria; Lechuga, Rodrigo; Garcia-Solis, Pablo; Garcia-Gutierrez, David G; Garcia-Solis, Marco Vinicio; Saenz de Viteri, Manuel; Solis-S, Juan C

    2017-01-01

    AIM To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). METHODS A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. RESULTS In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P=0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963: D'=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963: D'=0.505, r2=0.0214, P=0.142. CONCLUSION This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that

  14. Pharmacy Staff Opinions Regarding Diabetic Retinopathy Screenings in the Community Setting: Findings from a Brief Survey

    PubMed Central

    Law, Miranda G.; Komura, Stephanie; Murchison, Ann P.; Pizzi, Laura T.

    2013-01-01

    Background Diabetic retinopathy is a retinal vascular disorder that affects more than 4.1 million people in the United States. New methods of detecting and ensuring adequate follow-up of this life-altering disease are vital to improving patient outcomes. Wills Eye Hospital and the Centers for Disease Control and Prevention are conducting a collaborative study to initiate a novel diabetic retinopathy screening in the community setting. Objective To evaluate the feasibility of a more widespread, large-scale implementation of this novel model of care for diabetic retinopathy screening in the community setting. Methods A simple, self-administered survey was distributed to pharmacists, pharmacy technicians, student pharmacists, and Wills Eye Hospital interns. The survey consisted of open-ended questions and responders were given 1 week to respond. A total of 22 surveys were distributed and 16 were completed. The responses were culled and analyzed to assess the feasibility of implementing this novel screening model in the pharmacy. Results The response rate to this pilot survey was 72%. The majority of the responding pharmacy staff members indicated that diabetic retinopathy screening in community pharmacies would greatly benefit patients and could improve patient care. However, they also noted barriers to implementing the screening, such as concerns about the cost of carrying out the screenings, the cost of the equipment needed to be purchased, and the lack of time and shortage of pharmacy staff. Conclusion The potential exists for pharmacists to positively influence diabetes care by implementing retinopathy care through the early detection of the disease and reinforcement of the need for follow-up; however, real-world barriers must be addressed before widespread adoption of such a novel model of care becomes feasible. PMID:24991381

  15. 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

  16. 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

  17. The course of nonproliferative diabetic retinopathy following ECCE with posterior chamber IOL implantation.

    PubMed

    Raniel, Y; Teichner, Y; Friedman, Z

    1994-01-01

    A prospective study on the effect of ECCE + IOL implantation on the course of diabetic retinopathy (DR) in 59 eyes showed that in one to three years following surgery, progression of DR, including the development of newly formed one, occurred in 28.8% of the eyes. This was more marked in patient with IDDM (IDDM-46%, NIDDM-24%) as well as in eyes with pre-operative BDR (pre-operative BDR-62.5%, no pre-operative BDR-16.3%). Final visual acuity was better in eyes without pre-operative DR as well as in eyes that did not show progression of the retinopathy.

  18. Characterization of a novel polymorphism in PPARG regulatory region associated with type 2 diabetes and diabetic retinopathy in Italy.

    PubMed

    Costa, Valerio; Casamassimi, Amelia; Esposito, Katherine; Villani, Angela; Capone, Mariaelena; Iannella, Rosa; Schisano, Bruno; Ciotola, Miryam; Di Palo, Carmen; Corrado, Feliciantonia Capone; Santangelo, Franco; Giugliano, Dario; Ciccodicola, Alfredo

    2009-01-01

    Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes-particularly diabetic women with the proliferative retinopathy-were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not.

  19. 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

  20. CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina.

    PubMed

    Wang, Jing; Lin, Jihong; Schlotterer, Andreas; Wu, Liang; Fleming, Thomas; Busch, Stephanie; Dietrich, Nadine; Hammes, Hans-Peter

    2014-10-01

    Diabetes induces vasoregression, neurodegeneration and glial activation in the retina. Formation of advanced glycation endoproducts (AGEs) is increased in diabetes and contributes to the pathogenesis of diabetic retinopathy. CD74 is increased in activated microglia in a rat model developing both neurodegeneration and vasoregression. In this study, we aimed at investigating whether glucose and major AGE precursor methylglyoxal induce increased CD74 expression in the retina. Expression of CD74 in retinal microglia was analyzed in streptozotocin-diabetic rats by wholemount immunofluorescence. Nondiabetic mice were intravitreally injected with methylglyoxal. Expression of CD74 was studied by retinal wholemount immunofluorescence and quantitative real-time PCR, 48 h after the injection. CD74-positive cells were increased in diabetic 4-month retinas. These cells represented a subpopulation of CD11b-labeled activated microglia and were mainly located in the superficial vascular layer (13.7-fold increase compared to nondiabetic group). Methylglyoxal induced an 9.4-fold increase of CD74-positive cells in the superficial vascular layer and elevated gene expression of CD74 in the mouse retina 2.8-fold. In summary, we identified CD74 as a microglial activation marker in the diabetic retina. Exogenous methylglyoxal mimics the response in normoglycemic retina. This suggests that methylglyoxal is important in mediating microglial activation in the diabetic retina.

  1. Automated segmentation of retinal blood vessels and identification of proliferative diabetic retinopathy.

    PubMed

    Jelinek, Herbert F; Cree, Michael J; Leandro, Jorge J G; Soares, João V B; Cesar, Roberto M; Luckie, A

    2007-05-01

    Proliferative diabetic retinopathy can lead to blindness. However, early recognition allows appropriate, timely intervention. Fluorescein-labeled retinal blood vessels of 27 digital images were automatically segmented using the Gabor wavelet transform and classified using traditional features such as area, perimeter, and an additional five morphological features based on the derivatives-of-Gaussian wavelet-derived data. Discriminant analysis indicated that traditional features do not detect early proliferative retinopathy. The best single feature for discrimination was the wavelet curvature with an area under the curve (AUC) of 0.76. Linear discriminant analysis with a selection of six features achieved an AUC of 0.90 (0.73-0.97, 95% confidence interval). The wavelet method was able to segment retinal blood vessels and classify the images according to the presence or absence of proliferative retinopathy.

  2. 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.

  3. [The origin of papillary neovascularization in patients with proliferative diabetic retinopathy].

    PubMed

    Sdobnikova, S V; Mazurina, N K

    2004-01-01

    The case study covers examinations of 63 patients with diabetes mellitus (DM), type 1, and with proliferative diabetic retinopathy (PDR). According to the results of fluorescence angiography, the patients were shared between 3 groups: Group 1--early contrasting of papillary vascular neoplasms; Group 2--late contrasting; and Group 3--mixed contrasting. We explained the available differences by that the vascular neoplasms of the optic nerve disk (OND) originate from 2 main blood supply basins, i.e. choroidal and retinal ones. They reflect, with respect to the above stated, the hemodynamic properties of the choroidal mycocirculation, which is characterized by a higher hemodynamic load and a higher intravascular pressure, or the retinal hemomicrocirculation. The pathological signs of diabetic retinopathy in the choroidal system may fail to correlate with changes in the retinal vascular system itself. Therefore, the findings of fluorescence angiography do not always represent the genuine scope of pathological manifestations occurring in the hemomicrocirculation system in case of PDR.

  4. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier.

    PubMed

    Kaya, Abdullah; Kar, Taner; Aksoy, Yakup; Özalper, Veysel; Başbuğ, Barbaros

    2013-12-01

    Diabetic retinopathy regresses after spontaneous infarction or surgical ablation of pituitary gland. Growth hormone deficiency seems to be a protective factor for development of diabetic retinopathy in dwarfs. Despite the same glycemic control, development of diabetic retinopathy is significantly higher in pubertal subjects than pre-pubertal subjects. These evidences indicate a strong relationship between growth hormone and progression of diabetic retinopathy. Insulin like growth factor-1 (IGF-1) is the most important mediator of effects of growth hormone (GH). It stimulates IGF-1 receptor. Insulin analogues also stimulate IGF-1 receptor. Therefore insulin analogues may show similar effects like growth hormone and deteriorate diabetic retinopathy. However we suggest that impairment degree of inner blood-retinal barrier should be considered for this claim. We hypothesize that insulin analogues have dual effects (beneficial and worsening) depending on stage of impairment of inner blood-retinal barrier. Insulin analogues protect pericytes and blood-retinal barrier by decreasing blood glucose level. Analogues may pass into the retinal tissue in very low amounts when inner blood-retinal barrier is intact. Therefore, insulin analogues may not deteriorate diabetic retinopathy but also have beneficial effect by protecting blood-retinal barrier at this stage. However, they may pass into the retinal tissue in much more amounts when inner blood-retinal barrier impairs. Analogues may deteriorate cellular composition of retina through stimulation of IGF-1 receptors. A number of different cell types, including glia, retinal pigment epithelial cells and fibroblast-like cells have been identified in diabetic epiretinal tissues. Insulin analogues may cause proliferation in these cells. A type of glial cell named Non-astrocytic Inner Retinal Glia-like (NIRG) cell was identified to be stimulated and proliferate by IGF-1. IGF has been reported to generate traction force in retinal

  5. More Impact of Microalbuminuria on Retinopathy Than Moderately Reduced GFR Among Type 2 Diabetic Patients

    PubMed Central

    Chen, Yu-Hsin; Chen, Harn-Shen; Tarng, Der-Cherng

    2012-01-01

    OBJECTIVE The current study aimed to investigate whether microalbuminuria or moderately decreased glomerular filtration rate (GFR) is a better predictor for the development and progression of retinopathy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Type 2 diabetic patients without cardiovascular diseases, malignancy, pregnancy, and acute intercurrent illness were enrolled between 1 August 2001 and 31 December 2002. All participants provided their detailed medical history and underwent an eye fundus examination. They were followed up in outpatient clinics, and serum creatinine, urinary albumin-to-creatinine ratio (UACR), and retinal photographs were followed up annually until 31 December 2009. The primary outcomes were development and progression of diabetic retinopathy and nephropathy. The secondary outcomes were cardiovascular events and all-cause mortality. RESULTS Among 487 participants, 81 subjects had normoalbuminuria and moderate renal impairment (baseline eGFR 30–59.9 mL/min/1.73 m2), and 106 subjects had microalbuminuria and baseline eGFR ≥60 mL/min/1.73 m2. Patients with microalbuminuria and eGFR ≥60 mL/min/1.73 m2 had a significantly greater risk for development and progression of diabetic retinopathy (HR 3.34 [95% CI 1.04–10.70]) compared with those with moderate renal impairment and normoalbuminuria after multivariate adjustment. Risks for renal outcome, cardiovascular events, and all-cause mortality were not significantly different between the two groups. CONCLUSIONS Microalbuminuria has a greater impact on predicting the development and progression of diabetic retinopathy compared with moderate decline in GFR among type 2 diabetic patients. PMID:22338100

  6. Visual Acuity, Retinal Sensitivity, and Macular Thickness Changes in Diabetic Patients without Diabetic Retinopathy after Cataract Surgery.

    PubMed

    Stunf Pukl, Spela; Vidović Valentinčič, Nataša; Urbančič, Mojca; Irman Grčar, Irena; Grčar, Rok; Pfeifer, Vladimir; Globočnik Petrovič, Mojca

    2017-01-01

    Aim. Functional and morphological macular study after cataract surgery in a group of diabetics without diabetic retinopathy compared to nondiabetics to evaluate the effect of surgical oxidative stress on diabetic retina. Methods. Prospective, comparative study. Preoperative eye exam, best corrected visual acuity (BCVA) measured by ETDRS letters, and optical coherence tomography (OCT) were followed by standard cataract surgery. The follow-up visits at 1, 3, and 6 months postoperatively included BCVA, OCT, and microperimetry, to analyze changes within and between the groups. Results. The BCVA improved significantly in diabetics and controls: 64.2 to 81.0 and 61.9 to 82.1 ETDRS at 6 months, respectively. The central macula at OCT significantly thickened in both groups, while the central 5 fields, corresponding to the microperimetry area, subclinically thickened from 284.20 to 291.18 μm at 6 months only in diabetics (p = 0.026). A matching slight decrease in the microperimetry sensitivity from 1 to 6 months was found also only in diabetics, with mean average difference -0.75 dB (p = 0.04). Conclusion. Underlying diabetes does not influence the surgical outcome in diabetics without diabetic retinopathy. However, slight thickening of wider macula and corresponding decrease in retinal sensitivity observed in diabetics 6 months postoperatively might influence visual function on long term.

  7. Visual Acuity, Retinal Sensitivity, and Macular Thickness Changes in Diabetic Patients without Diabetic Retinopathy after Cataract Surgery

    PubMed Central

    Irman Grčar, Irena; Grčar, Rok; Pfeifer, Vladimir

    2017-01-01

    Aim. Functional and morphological macular study after cataract surgery in a group of diabetics without diabetic retinopathy compared to nondiabetics to evaluate the effect of surgical oxidative stress on diabetic retina. Methods. Prospective, comparative study. Preoperative eye exam, best corrected visual acuity (BCVA) measured by ETDRS letters, and optical coherence tomography (OCT) were followed by standard cataract surgery. The follow-up visits at 1, 3, and 6 months postoperatively included BCVA, OCT, and microperimetry, to analyze changes within and between the groups. Results. The BCVA improved significantly in diabetics and controls: 64.2 to 81.0 and 61.9 to 82.1 ETDRS at 6 months, respectively. The central macula at OCT significantly thickened in both groups, while the central 5 fields, corresponding to the microperimetry area, subclinically thickened from 284.20 to 291.18 μm at 6 months only in diabetics (p = 0.026). A matching slight decrease in the microperimetry sensitivity from 1 to 6 months was found also only in diabetics, with mean average difference −0.75 dB (p = 0.04). Conclusion. Underlying diabetes does not influence the surgical outcome in diabetics without diabetic retinopathy. However, slight thickening of wider macula and corresponding decrease in retinal sensitivity observed in diabetics 6 months postoperatively might influence visual function on long term. PMID:28243608

  8. Proliferative retinopathy and neovascularization of the anterior segment in female type 2 diabetic rats

    PubMed Central

    2013-01-01

    Background To examine the presence of diabetic retinopathy in a female rat model of type 2 diabetes fed on a high-fat diet (HFD). Methods Wistar rats were injected with streptozotocin (STZ) at the age of two days and fed on an HFD from eight weeks onwards. Five diabetic animals were euthanized at 110 weeks of disease, together with a control group of age-matched, non-diabetic animals. A group of diabetic animals at 57 weeks of disease was included for comparison. Cross sections of the rats’ corneas, iris and retinas were histologically examined and analysed by immunohistochemistry and immunofluorescence, using glial-fibrillary-acidic-protein (GFAP), the vascular endothelial growth factor (VEGF) and the Von Willebrand factor (vWF). The trypsine digestive technique was used for the pericytes count. Results Neovascularization was only found in the retinas, irises and corneas of the diabetic animals of 110 weeks of disease. There was also a significantly lower number of pericytes in these animals than in the controls. Conclusion The female rat model of type 2 diabetes fed on an HFD may prove useful in evaluating the mechanisms involved in diabetic retinopathy, together with strategies to reduce its severity. PMID:24499599

  9. Emerging Roles of Transforming Growth Factor β Signaling in Diabetic Retinopathy.

    PubMed

    Wheeler, Sarah E; Lee, Nam Y

    2017-03-01

    Diabetic retinopathy (DR) is a serious complication of diabetes mellitus affecting about one third of diabetic adults. Despite its prevalence, treatment options are limited and often implemented only in the later stages of the disease. To date, the pathogenesis of DR has been extensively characterized in the context of elevated glucose, insulin, and VEGF signaling, although a growing number of other growth factors and molecules, including transforming growth factor β (TGF-β) are being recognized as important contributors and/or therapeutic targets. Here, we review the complex roles of TGF-β signaling in DR pathogenesis and progression. J. Cell. Physiol. 232: 486-489, 2017. © 2016 Wiley Periodicals, Inc.

  10. Information fusion for diabetic retinopathy CAD in digital color fundus photographs.

    PubMed

    Niemeijer, Meindert; Abramoff, Michael D; van Ginneken, Bram

    2009-05-01

    The purpose of computer-aided detection or diagnosis (CAD) technology has so far been to serve as a second reader. If, however, all relevant lesions in an image can be detected by CAD algorithms, use of CAD for automatic reading or prescreening may become feasible. This work addresses the question how to fuse information from multiple CAD algorithms, operating on multiple images that comprise an exam, to determine a likelihood that the exam is normal and would not require further inspection by human operators. We focus on retinal image screening for diabetic retinopathy, a common complication of diabetes. Current CAD systems are not designed to automatically evaluate complete exams consisting of multiple images for which several detection algorithm output sets are available. Information fusion will potentially play a crucial role in enabling the application of CAD technology to the automatic screening problem. Several different fusion methods are proposed and their effect on the performance of a complete comprehensive automatic diabetic retinopathy screening system is evaluated. Experiments show that the choice of fusion method can have a large impact on system performance. The complete system was evaluated on a set of 15,000 exams (60,000 images). The best performing fusion method obtained an area under the receiver operator characteristic curve of 0.881. This indicates that automated prescreening could be applied in diabetic retinopathy screening programs.

  11. Diagnosing and ranking retinopathy disease level using diabetic fundus image recuperation approach.

    PubMed

    Somasundaram, K; Rajendran, P Alli

    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.

  12. Diabetic retinopathy equity profile in a multi-ethnic, deprived population in Northern England

    PubMed Central

    Kliner, M; Fell, G; Gibbons, C; Dhothar, M; Mookhtiar, M; Cassels-Brown, A

    2012-01-01

    Purpose Equity profiles are an established public health tool used to systematically identify and address inequity within health and health services. Our aim was to conduct an equity profile to identify inequity in eye health across Leeds and Bradford. This paper presents results of findings for diabetic retinopathy in Bradford and Airedale. Methods A variety of routine health data were included and sub-analysed by measures of equity, including age, sex, ethnicity, and deprivation to identify inequity in eye health and healthcare. The Spearman Rank Correlation Coefficient was used to determine the association between variables. Results The prevalence of diagnosed diabetes in Bradford and Airedale district is 6.6% compared to 4.3% in nearby Leeds and 5.1% nationally. The age-standardised prevalence of diagnosed diabetic retinopathy within Bradford and Airedale is 2.21% (95% CI 1.54–2.26%), with a disproportionately high prevalence of disease in the Pakistani population and the most deprived parts of the population. There was a poorer uptake of diabetic retinopathy screening in more deprived parts of the district and the proportions with a higher rate of referral to ophthalmology following the screening in Black and Minority Ethnic populations compared with the white population (13.2% vs6.9%). Uptake of secondary care outpatient appointments is much lower in more deprived populations. Conclusion Inequalities are inherent in diabetic retinopathy prevalence, diagnosis, and treatment. The reasons for these inequities are multi-factorial and further investigation of reasons for poor uptake of services is required. Addressing the inequalities in eye health and healthcare requires cross-organisational collaboration. PMID:22302063

  13. Association between transcription factor 7-like 2 rs7903146 polymorphism and diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis.

    PubMed

    Ding, Yuzhi; Hu, Zizhong; Yuan, Songtao; Xie, Ping; Liu, Qinghuai

    2015-11-01

    As one of the vascular complications of type 2 diabetes mellitus, the incidence of diabetes retinopathy is greatly increasing worldwide. Both genetic and environmental factors are involved in the pathologies. A meta-analysis was conducted to assess the association between transcription factor 7-like 2 polymorphism (rs7903146) and type 2 diabetic retinopathy. Published literature from PubMed, Web of Science and China National Knowledge Infrastructure were retrieved. Pooled odds ratios with 95% confidence intervals were calculated to estimate the strength of the association. Eight studies including 6422 participants were included in the final meta-analysis. Our analysis provides substantial evidence that the rs7903146 variant is significantly associated with the risk of diabetic retinopathy in Caucasian populations while not in East Asian populations. The variant of rs7903146 appeared more likely to be a promising genetic biomarker of diabetic retinopathy in Caucasians.

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

    PubMed Central

    Rahimi, Zohreh; Moradi, Mahmoudreza; Nasri, Hamid

    2014-01-01

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

  15. Prevalence and incidence of retinopathy in elderly diabetic patients receiving early diagnosis and treatment

    PubMed Central

    LI, XIN; WANG, ZHAOYAN

    2013-01-01

    Diabetic retinopathy (DR) is one of the most common and specific complications of diabetes. Thus, intervention is required to lower the incidence and prevalence of sight-threatening retinopathy. The aim of this study was to investigate the prevalence and incidence of diabetic retinopathy in elderly diabetic patients receiving early diagnosis and proper treatment and to explore risk factors for DR. From May 2005 to May 2011, fundus examination was performed for elderly diabetic patients during routine medical examinations. The presence of a microaneurysm or more severe presentations was used to diagnose DR, which was followed by fundus fluorescein angiography. Logistic regression analysis was employed to analyze the risk factors for DR development within 5 years. A total of 2,194 diabetic patients were recruited and followed-up for a mean of 5.8 years. The prevalence of DR was 15.38–16.20% and the incidence of DR was 8.38/1,000 person-years. Logistic multiple stepwise regression revealed that fasting plasma glucose (FPG), mean arterial pressure (MAP), duration of diabetes, body mass index (BMI) and microalbuminuria (MAU) were significantly associated with the occurrence of DR (all P<0.05). In the present study, the prevalence and incidence of DM were higher compared with those reported in the general population; however, the prevalence and incidence of DR were lower compared with those reported in similar studies. This suggests that favorable control of blood glucose, blood pressure and blood lipids effectively prevents the occurrence of DR in diabetic patients. PMID:23737887

  16. Dynamic DNA methylation of matrix metalloproteinase-9 in the development of diabetic retinopathy

    PubMed Central

    Kowluru, Renu A.; Shen, Yang; Mishra, Manish

    2016-01-01

    Diabetes elevates matrix metalloproteinase-9 (MMP-9) in the retina and its capillary cells, and activated MMP-9 damages mitochondria, accelerating retinal capillary cell apoptosis, a phenomenon which precedes the development of retinopathy. Diabetes also favors epigenetic modifications regulating expression of many genes. DNA methylation is maintained by methylating-hydroxymethylating enzymes, and retinal DNA methyltransferase (Dnmt) is activated in diabetes. Our aim is to investigate the role of DNA methylation in MMP-9 regulation. Effect of high glucose on 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and binding of Dnmt1 and hydroxymethylating enzyme (Tet2) on MMP-9 promoter were quantified in retinal endothelial cells. Specific role of Tet2 in MMP-9 activation was validated using Tet2-siRNA. The results were confirmed in the retina from streptozotocin-induced diabetic mouse. Although glucose increased Dnmt1 binding at MMP-9 promoter, it decreased 5mC levels. At the same promoter site, Tet2 binding and 5hmC levels were elevated. Tet2-siRNA ameliorated increase in 5hmC and MMP-9 transcription, and protected mitochondrial damage. Diabetic mice also presented similar dynamic DNA methylation changes in the retinal MMP-9 promoter. Thus, in diabetes transcription of retinal MMP-9 is maintained, in part, by an active DNA methylation-hydroxymethylation process, and regulation of this machinery should help maintain mitochondrial homeostasis and inhibit the development/ progression of diabetic retinopathy. PMID:27454437

  17. 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.

  18. Comparison of Efficacy and Side Effects of Multispot Lasers and Conventional Lasers for Diabetic Retinopathy Treatment

    PubMed Central

    Çeliker, Hande; Erdağı Bulut, Azer; Şahin, Özlem

    2017-01-01

    Panretinal photocoagulation (PRP) is a standard treatment for proliferative diabetic retinopathy. Conventional laser (CL) therapy is performed in one or more sessions in single spot mode. Visual disabilities have been reported after treatment with CL, including central vision loss due to macular edema and peripheral visual field loss resulting from extensive inner retinal scarring. Multispot laser (MSL) photocoagulation has recently been introduced to clinical practice. Studies comparing PRP conducted with MSL and CL have reported that MSLs resulted in less retinal tissue damage and pain, and greater patient comfort compared to CL. The aim of this review was to compare the efficacy and side effects of MSLs and CLs for diabetic retinopathy treatment. PMID:28182169

  19. Downregulated Brain-Derived Neurotrophic Factor-Induced Oxidative Stress in the Pathophysiology of Diabetic Retinopathy.

    PubMed

    Behl, Tapan; Kotwani, Anita

    2017-04-01

    Brain-derived neurotrophic factor (BDNF), a member of neurotrophin growth factor family, physiologically mediates induction of neurogenesis and neuronal differentiation, promotes neuronal growth and survival and maintains synaptic plasticity and neuronal interconnections. Unlike the central nervous system, its secretion in the peripheral nervous system occurs in an activity-dependent manner. BDNF improves neuronal mortality, growth, differentiation and maintenance. It also provides neuroprotection against several noxious stimuli, thereby preventing neuronal damage during pathologic conditions. However, in diabetic retinopathy (a neuromicrovascular disorder involving immense neuronal degeneration), BDNF fails to provide enough neuroprotection against oxidative stress-induced retinal neuronal apoptosis. This review describes the prime reasons for the downregulation of BDNF-mediated neuroprotective actions during hyperglycemia, which renders retinal neurons vulnerable to damaging stimuli, leading to diabetic retinopathy.

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

    PubMed Central

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

    2016-01-01

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

  1. Stronger relationship of serum apolipoprotein A-1 and B with diabetic retinopathy than traditional lipids

    PubMed Central

    Ankit, B. S.; Mathur, G.; Agrawal, R. P.; Mathur, K. C.

    2017-01-01

    Aim: Diabetic retinopathy (DR) is the most common preventable cause of blindness where early detection and treatment can be sight-saving. Search for biomarkers of the disease has been relentless. We aimed to determine whether lipoproteins apolipoproteins A1 and B1 (Apo-A1 and Apo-B1) have stronger associations with DR in contrast to conventionally measured low-density lipoprotein (LDL) and high-density lipoprotein cholesterol levels. Materials and Methods: We performed a cross-sectional study and studied 117 patients. Serum lipid profile was assessed by autoanalyzer. Serum Apo-A1 and Apo-B were measured using immunoturbidimetric kit on an autoanalyzer. Apo-B/A1 ratio was calculated. Retinopathy was graded from the digital retinal photographs, taken with nonmydriatic auto fundus camera and classified according to International Clinical DR Disease Severity Scale. Results: Mean Apo-A1 for mild, moderate, severe retinopathy, and proliferative DR (PDR) shows a significant negative correlation (P = 0.001) with severity of retinopathy. Mean Apo-B for mild, moderate, severe, PDR displayed a significant positive correlation with severity of retinopathy (P = 0.001). Mean Apo-B/A1 for mild, moderate, severe, PDR showed highly significant positive correlation with severity of retinopathy (P < 0.001). In contrast, mean LDL for mild, moderate, severe, PDR showed insignificant association with severity of DR (P = 0.081). Conclusion: Apo-A1 and Apo-B have a stronger association with the development of DR than traditional lipids and can thus facilitate early detection and treatment of the disease. PMID:28217507

  2. Danish Nationwide Data Reveal a Link between Diabetes Mellitus, Diabetic Retinopathy, and Glaucoma

    PubMed Central

    Petrovski, Beáta Éva; Torp-Pedersen, Christian

    2016-01-01

    Aims. To determine the association between treatment against diabetes mellitus (DM) and treatment with antiglaucomatous drugs in the entire Danish population and to investigate the comorbidity between DM and its complications with antiglaucomatous treatment. Methods. Retrospective nationwide cohort study with data over a 16-year follow-up period. The National Danish Registry of Medicinal Products Statistics was used to identify all claimed prescriptions for antiglaucomatous medication and DM drugs. ICD-10 classifications were furthermore used to identify comorbidities between antiglaucomatous medication and the DM complications, diabetic retinopathy (DR), and nephropathy. Results. A total of 6,343,747 individuals in the period between 1996 and 2012 were analyzed. The overall incidence rate of new-onset glaucoma patients was 0.07 per 1000 person-years for the reference population compared to 36 per 1000 person-years for all diagnosed DM cases. Patients treated with DM drugs had about two times higher relative risk of glaucoma, when adjusting for a range of factors. The presence of DR alone or in combination with nephropathy increased the risk of glaucoma. Conclusions. The present study reports a strong association between DM and onset of glaucoma treatment in the entire Danish population. PMID:27872861

  3. Glucocorticoids: structure, signaling and molecular mechanisms in the treatment of diabetic retinopathy and diabetic macular edema.

    PubMed

    Zhang, X; Wang, N; Schachat, A P; Bao, S; Gillies, M C

    2014-03-01

    Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and dyslipidemia. Ocular treatments include vascular endothelial growth factor A (VEGF-A) inhibitors, laser photocoagulation and surgery. While anti-VEGF therapy has become as first-line treatment for diabetic macular edema (DME) that causes reduced vision, intravitreal glucocorticoids also have been shown to be efficacious in this situation. It has been reported that all the major pathological processes of DR are susceptible to glucocorticoid treatment. The effects of glucocorticoids on vascular leakage and angiogenesis may be mediated through their well established anti-inflammatory role. Alternatively, glucocorticoids may affect other mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of glucocorticoids include blockage of cytokine production and inhibition of leukocyte adhesion induced by VEGF-A. Glucocorticoids decrease the expression of VEGF-A directly, and increase the production, or decrease phosphorylation, of tight junction-associated proteins. Glucocorticoids have also been shown to be neuroprotective, in contrast to VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review outlines the biological properties of synthetic glucocorticoids, with particular emphasis on the potential beneficial effect of combining glucocorticoids with anti-VEGF treatment for DME and DR.

  4. Inverse Association between Serum Bilirubin Levels and Retinopathy in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Venkatesan, Raghuram; Thankappan, Lekha; Andavar, Raghuram; Devisundaram, Sundar

    2017-01-01

    Introduction Oxidative stress plays a central role in the pathogenesis of Diabetic Retinopathy (DR) and serum bilirubin has been shown to have antioxidant properties. Aim To investigate the association between serum bilirubin concentration and DR in patients with Type 2 Diabetes Mellitus (DM). Materials and Methods This was a hospital based, cross- sectional study where in 86 patients with Type 2 DM and 30 controls were recruited. The study was conducted at a tertiary care centre in Southern India between January 2014 and December 2014. The presence and the severity of DR were determined by fundus examination and grading of colour fundus photographs using the international clinical disease severity scale for DR. Serum total, direct and indirect bilirubin levels were determined in all subjects and the association between bilirubin levels and severity of DR was studied. Results Among the 86 diabetics, 24 had no retinopathy and 62 had DR of varying grades. The mean total bilirubin level among diabetic subjects (0.52±0.17) and controls (0.51±0.19) were found to be similar. The mean total as well as direct bilirubin levels were found to be lower in patients with retinopathy as compared to no retinopathy group (p<0.001). The severity of DR was inversely proportional to the serum bilirubin levels (p=0.010). Serum total bilirubin was found to have a negative association with glycosylated haemoglobin and served as an independent determinant of DR even after adjusting for risk factors known to be associated with DR (p=0.001). Conclusion Low serum bilirubin levels are significantly associated with increased risk of DR independent of classic risk factors. Serum bilirubin can serve as a useful biomarker in identifying patients at risk for developing proliferative DR. PMID:28384901

  5. Fulminant proliferative diabetic retinopathy in the non-photocoagulated eye following acute renal failure.

    PubMed

    Jang, Liuna; Herbort, Carl P

    2016-12-01

    Management of diabetic retinopathy should follow more strict and aggressive rules in patients at risk for severe acute renal impairment. Such patients should be identified and possibly prophylactically laser treated to avoid the severe consequences demonstrated in this case report. A 34-year-old type 2 diabetes patient with a stabilized diabetic retinopathy developed acute and severe retinal decompensation within weeks after acute renal failure complicated his chronic stable renal impairment. Fluorescein angiographic and optical coherence tomographic illustrations of the rapid evolution of the retinal condition are presented. The patient had previously been treated with panretinal photocoagulation in his left eye. After 8 years of regular 6-monthly checked stability, he developed rapid-onset proliferative diabetic retinopathy and macular edema in his right eye within 3 months of his last ocular check-up. Fluorescein angiography showed neovessels and major ischemic areas. Emergency panretinal photocoagulation and a sub-Tenon's injection were necessary to achieve control of the situation with regression of neovessels and complete regression of macular edema. This case shows that it is imperative for nephrologists to be well informed about a patient's ocular situation in order to give timely information to the ophthalmologist who can intervene to protect the retina in case of renal failure. On the other hand, the ophthalmologist should be familiar with the renal function of his patient with renal impairment so that he can decide to perform prophylactic retinal panphotocoagulation that should be imperatively considered even without strict indications in patients with renal impairment at risk for further deterioration of renal function, in order to prevent such explosive ischemic and proliferative retinopathy putting vision at risk.

  6. Assessment of calcium dobesilate in diabetic retinopathy. A double-blind clinical investigation.

    PubMed

    Salama Benarroch, I; Nano, H; Pérez, H; Elizalde, F; Bisceglia, H; Salama, A

    1977-01-01

    In this double-blind, randomized trial, which lasted for 2 years, the authors investigated the efficacy of calcium dobesilate on diabetic retinopathy. 68 patients (51 on the active substance, 17 on placebo) participated in the study. The statistical analysis of the results indicate that calcium dobesilate acts as a potent angioprotector, capable of preventing both intra and extraretinal hemorrhages. The drug also lowers the incidence of exudate formation and improves visual acuity.

  7. 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.

  8. Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections

    PubMed Central

    Levin, Ariana M; Rusu, Irene; Orlin, Anton; Gupta, Mrinali P; Coombs, Peter; D’Amico, Donald J; Kiss, Szilárd

    2017-01-01

    Purpose The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. Methods This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Results Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. Conclusion In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA. PMID:28176934

  9. Oral Administration of Cilostazol Increases Ocular Blood Flow in Patients with Diabetic Retinopathy

    PubMed Central

    Hwang, Duck Jin; Shin, Joo Young

    2017-01-01

    Purpose To investigate the effect of cilostazol on ocular hemodynamics and to determine whether the administration of cilostazol increases the ocular blood flow in patients with diabetic retinopathy. Methods This prospective observational study investigated the effect of orally administered cilostazol on diabetic retinopathy. Before and after administration for 1 week, pulsatile ocular blood flow (POBF) and retrobulbar hemodynamics were measured using a POBF analyzer and transcranial Doppler imaging, respectively. Visual acuity, intraocular pressure, and blood pressure were also evaluated before and after treatment. Results Twenty-five eyes of 25 patients were included in this study. POBF increased significantly (16.8 ± 4.6 µL/sec vs. 19.6 ± 6.2 µL/sec, p < 0.001) after administration of cilostazol, while no significant change was identified in visual acuity, intraocular pressure, and blood pressure. Mean flow velocity in the ophthalmic artery as measured with transcranial Doppler imaging also increased significantly after medication (23.5 ± 5.6 cm/sec vs. 26.0 ± 6.9 cm/sec, p = 0.001). The change in POBF directly correlated with the change in mean flow velocity (r = 0.419, p = 0.007). Conclusions Cilostazol was effective in increasing ocular blood flow in patients with diabetic retinopathy, possibly by modulating retrobulbar circulation. PMID:28367040

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

    PubMed Central

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

    2016-01-01

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

  11. 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

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

    PubMed

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

    2015-02-01

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

  13. 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

  14. [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.

  15. Serum magnesium, iron and ferritin levels in patients with diabetic retinopathy attending Makkah Eye Complex, Khartoum, Sudan.

    PubMed

    Hamdan, Hamdan Z; Nasser, Nasser M; Adam, Ammar M; Saleem, Mahgoub A; Elamin, Maha I

    2015-05-01

    Diabetic retinopathy is the most common complications of diabetes mellitus that, in most occasions, lead to blindness. Multiple evidences linked the serum magnesium, iron and ferritin disturbance with diabetes and its complications. A case-control study was conducted at Makkah Eye Complex, Khartoum, Sudan, to compare the levels of serum magnesium, iron and ferritin in patients with diabetic retinopathy with diabetic patients without diabetic retinopathy (controls). Findings indicate that all patients had type 2 diabetes. The two groups (50 in each arm) were well matched in their basic characteristics. Median (25th-75th interquartile) of serum magnesium in patients with diabetic retinopathy were significantly lower than patients without diabetic retinopathy [1.48 (0.75-1.64) vs. 1.92 (1.4-2.3)mg/dl, P = 0.022]. The median of serum iron and ferritin were lower in cases than control group but did not reach a statistical significance [20.5 (17.2-48.0) vs. 27.0 (16.0-54.0) μg/dl, P = 0.568; 98.0 (45.0-134.75) vs. 101.0 (47.0-161.0) μg/l, P = 0.818]. The duration of diabetes [16.5 (9.3) vs. 11.2 (6.6) years; P = 0.014] and haemoglobin level [13.7 (0.9) vs. 12.5 (2.0) g/dl; P = 0.039] were significantly higher in cases group than control group. A significant inverse correlation was observed between serum magnesium and iron levels. Twenty (40 %) patients had severe non-proliferative diabetic retinopathy with mild macular edema, which is the most prevalent type among the cases group. Hypomagnesaemia among diabetic patients was associated with diabetic retinopathy, while serum iron and ferritin have no significant effect in this setting. Severe non-proliferative diabetic retinopathy with mild macular edema is the prevalent type in this study.

  16. Retinal ganglion cell complex changes using spectral domain optical coherence tomography in diabetic patients without retinopathy

    PubMed Central

    Hegazy, Ahmed I.; Zedan, Rasha H.; Macky, Tamer A.; Esmat, Soheir M.

    2017-01-01

    AIM To assess the ganglion cell complex (GCC) thickness in diabetic eyes without retinopathy. METHODS Two groups included 45 diabetic eyes without retinopathy and 21 non diabetic eyes. All subjects underwent full medical and ophthalmological history, full ophthalmological examination, measuring GCC thickness and central foveal thickness (CFT) using the RTVue® spectral domain-optical coherence tomography (SD-OCT), and HbA1C level. RESULTS GCC focal loss volume (FLV%) was significantly more in diabetic eyes (22.2% below normal) than normal eyes (P=0.024). No statistically significant difference was found between the diabetic group and the control group regarding GCC global loss volume (GLV%) (P=0.160). CFT was positively correlated to the average, superior and inferior GCC (P=0.001, 0.000 and 0.001 respectively) and negatively correlated to GLV% and FLV% (P=0.002 and 0.031 respectively) in diabetic eyes. C/D ratio in diabetic eyes was negatively correlated to average, superior and inferior GCC (P=0.015, 0.007 and 0.017 respectively). The FLV% was negatively correlated to the refraction and level of HbA1c (P=0.019 and 0.013 respectively) and positively correlated to the best corrected visual acuity (BCVA) in logMAR in diabetic group (P=0.004). CONCLUSION Significant GCC thinning in diabetes predates retinal vasculopathy, which is mainly focal rather than diffuse. It has no preference to either the superior or inferior halves of the macula. Increase of myopic error is significantly accompanied with increased focal GCC loss. GCC loss is accompanied with increased C/D ratio in diabetic eyes. PMID:28393035

  17. The period effect in the prevalence of proliferative diabetic retinopathy, gross proteinuria, and peripheral neuropathy in type 1 diabetes: A longitudinal cohort study

    PubMed Central

    Horak, Kayla; Lee, Kristine E.; Klein, Barbara E. K.; Klein, Ronald

    2017-01-01

    Aims To investigate whether, for a specific duration of type 1 diabetes, there is a significant change in the prevalence of proliferative diabetic retinopathy, gross proteinuria and peripheral neuropathy in those more recently diagnosed with diabetes (a period effect), in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Where present, to determine how common risk factors for diabetic complications might be associated with it, and what might be driving it. Materials and methods Longitudinal cohort study with seven examination phases between 1980 and 2014. Multivariate logistic regression models and ordinal parameterization were used to test for and evaluate any period effect. Results There is a period effect in the prevalence of gross proteinuria and peripheral neuropathy (decreasing), as seen with proliferative diabetic retinopathy (p < 0.001). Adjusting for changing levels of common risk factors attenuates the period effect, particularly for proliferative diabetic retinopathy. For gross proteinuria and peripheral neuropathy, however there is a persistent period effect in spite of adjusting for the major risk factors. Conclusions There are period effects in the prevalence of proliferative diabetic retinopathy, gross proteinuria and peripheral neuropathy that cannot be fully explained by changes in common risk factors for complications of type 1 diabetes in this cohort. The role of other potential confounders warrants further exploration. PMID:28362881

  18. Incentives and barriers to retinopathy screening among African-Americans with diabetes.

    PubMed

    Walker, E A; Basch, C E; Howard, C J; Zybert, P A; Kromholz, W N; Shamoon, H

    1997-01-01

    Diabetes-related ophthalmic complications are the leading cause of newly diagnosed blindness among adults. These eye complications are often asymptomatic in the early stages, yet the majority of diabetes patients are not screened yearly. To develop a health promotion intervention to increase the rate of screening for diabetic retinopathy by dilated fundus exam (DFE), we assessed the knowledge and health beliefs related to preventing diabetic eye complications among a sample of African-Americans with diabetes. The study design was cross-sectional, using a telephone interview to collect data. From a random sample of 104 African-Americans with diabetes, 67 (64%) were completed: 54 women; mean age of 58 years. The telephone interview schedule contained items grouped into subscales for Perceived Incentives, Perceived Barriers to getting a DFE, Causes of Eye Problems, Risk of Eye Problems, and Effective Treatments for Eye Problems. Descriptive statistics were used to analyze the quantitative data. Transcribed qualitative responses to the open-ended questions were analyzed for themes. The incentives "having eye problems" and "doctor said it was important to go" each had 91% responding it was an incentive to go for a DFE. Only about one-third agreed that any particular item was a barrier to receiving a DFE (e.g., economic factors). In the subscale for Risk of Eye Problems, "retinopathy" had the lowest level of perceived risk (30%). Only 21% of the sample reported there were effective treatments for retinopathy. Eighty-seven percent reported the faulty belief that "diabetic eye problems have symptoms." Only 36% of the sample said they had heard of retinopathy and of those, only 8% could describe it correctly. Among general response themes were: fear, spirituality (faith and hope), priorities, economic or logistical factors, and external/internal motivation. Perceived incentives for receiving a DFE were acknowledged at far greater rates than perceived barriers. Having a

  19. Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy.

    PubMed

    Elahy, Mina; Baindur-Hudson, Swati; Cruzat, Vinicius F; Newsholme, Philip; Dass, Crispin R

    2014-09-01

    Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties.

  20. 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

  1. Radiation retinopathy.

    PubMed Central

    Zamber, R W; Kinyoun, J L

    1992-01-01

    Radiation therapy is effective against many cancerous and noncancerous disease processes. As with other therapeutics, side effects must be anticipated, recognized, and managed appropriately. Radiation retinopathy is a vision-threatening complication of ocular, orbital, periorbital, facial, nasopharyngeal, and cranial irradiation. Factors that appear important in the pathogenesis of radiation retinopathy include total radiation dosage, fraction size, concomitant chemotherapy, and preexisting vascular disorders. Clinical manifestations of the disorder include macular edema and nonproliferative and proliferative retinopathy, similar to changes seen in diabetic retinopathy. Argon laser photocoagulation has proved efficacious for managing macular edema and fibrovascular proliferation in some of these patients. Ongoing basic laboratory and clinical research efforts have led to a better understanding of the pathogenesis, natural history, and treatment response of radiation retinopathy. The ultimate goal of this knowledge is to improve the prevention, recognition, and management of this vision-threatening complication. Images PMID:1441494

  2. 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.

  3. 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

  4. Characterization of a Novel Polymorphism in PPARG Regulatory Region Associated with Type 2 Diabetes and Diabetic Retinopathy in Italy

    PubMed Central

    Costa, Valerio; Casamassimi, Amelia; Esposito, Katherine; Villani, Angela; Capone, Mariaelena; Iannella, Rosa; Schisano, Bruno; Ciotola, Miryam; Di Palo, Carmen; Capone Corrado, Feliciantonia; Santangelo, Franco; Giugliano, Dario; Ciccodicola, Alfredo

    2009-01-01

    Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes—particularly diabetic women with the proliferative retinopathy—were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not. PMID:19125195

  5. White Dots as a Novel Marker of Diabetic Retinopathy Severity in Ultrawide Field Imaging

    PubMed Central

    Dodo, Yoko; Murakami, Tomoaki; Unoki, Noriyuki; Ogino, Ken; Uji, Akihito; Yoshitake, Shin; Yoshimura, Nagahisa

    2016-01-01

    Purpose To characterize white dots in diabetic retinopathy (DR) and their association with disease severity using ultra-wide-field scanning laser ophthalmoscopy. Methods We randomly selected 125 eyes of 77 patients (25 eyes from individual categories of the international classification of DR severity) for which ultrawide field photographs were obtained. We characterized white dots, which were delineated by higher signal levels on green but not red laser images, and evaluated the relationship between the number of white dots and the international severity scale of DR. Results Most white dots were located in nonperfused areas, and the number of total white dots was significantly correlated to that of dots in nonperfused areas. White dots corresponded to microaneurysms around the boundary between nonperfused areas and perfused areas or unknown lesions in nonperfused areas. Eyes with DR had significantly more white dots than those with no apparent retinopathy. The numbers of white dots in moderate nonproliferative diabetic retinopathy (NPDR) or more severe grades were significantly higher than in mild NPDR. The area under the receiver operating characteristics curve (AROC) analyses demonstrated that the number of white dots had the significance in the diagnosis of DR (0.908–0.986) and moderate NPDR or more severe grades (0.888–0.974). Conclusions These data suggest the clinical relevance of white dots seen on ultrawide field images in the diagnosis of the severity of DR. PMID:27812207

  6. 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

  7. Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy

    PubMed Central

    Liao, Po-Lin; Lin, Cheng-Hui; Li, Ching-Hao; Tsai, Chi-Hao; Ho, Jau-Der; Chiou, George C. Y.; Kang, Jaw-Jou; Cheng, Yu-Wen

    2017-01-01

    Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O2) for quicker induction of early-stage retinopathy in C57BL/6 mice. We also compared the effects of a high glucose condition combined with hypoxia (1% O2) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy. In the retina of DM/hypoxic C57BL/6 mice, abnormal a-wave and b-wave activity, yellowish-white spots, hyperfluorescence, and reduced retinal thickness were found using electroretinography (ERG), fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Shikonin dose-dependently (0.5–50 mg/kg, per os) prevented DM/hypoxia-induced lesions. In eye tissue, administration of shikonin also attenuated DM/hypoxia-induced pre-apoptotic protein BAX expression as well as the production of inflammatory proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). We also demonstrated that shikonin administration rescues high glucose/hypoxia (1% O2)-induced inflammation, decreased junction protein expression, and permeability in RPE cells. These results indicate that shikonin treatment may prevent the loss of vision associated with DR. PMID:28322323

  8. Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

    PubMed Central

    Savolainen, Markku J.

    2016-01-01

    Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p = 0.001), and 76.1 (48.2) for NoDR (p = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p > 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR. PMID:28090539

  9. 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

  10. 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.

  11. A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy.

    PubMed

    Santos, Julia M; Tewari, Shikha; Kowluru, Renu A

    2012-11-01

    In the pathogenesis of diabetic retinopathy, an increase in retinal oxidative stress precedes mitochondrial dysfunction and capillary cell apoptosis. This study is designed to understand the mechanism responsible for the protection of mitochondria damage in the early stages of diabetic retinopathy. After 15 days-12 months of streptozotocin-induced diabetes in rats, retina was analyzed for mitochondria DNA (mtDNA) damage by extended length PCR. DNA repair enzyme and replication machinery were quantified in the mitochondria, and the binding of mitochondrial transcriptional factor A (TFAM) with mtDNA was analyzed by ChIP. Key parameters were confirmed in the retinal endothelial cells incubated in 20mM glucose for 6-96h. Although reactive oxygen species (ROS) were increased within 15 days of diabetes, mtDNA damage was observed at 6 months of diabetes. After 15 days of diabetes DNA repair/replication enzymes were significantly increased in the mitochondria, but at 2 months, their mitochondrial accumulation started to come down, and mtDNA copy number and binding of TFAM with mtDNA became significantly elevated. However, at 6 months of diabetes, the repair/replication machinery became subnormal and mtDNA copy number significantly decreased. A similar temporal relationship was observed in endothelial cells exposed to high glucose. Thus, in the early stages of diabetes, increased mtDNA biogenesis and repair compensates for the ROS-induced damage, but, with sustained insult, this mechanism is overwhelmed, and mtDNA and electron transport chain (ETC) are damaged. The compromised ETC propagates a vicious cycle of ROS and the dysfunctional mitochondria fuels loss of capillary cells by initiating their apoptosis.

  12. High Levels of Serum Prolactin Protect Against Diabetic Retinopathy by Increasing Ocular Vasoinhibins

    PubMed Central

    Arnold, Edith; Rivera, José C.; Thebault, Stéphanie; Moreno-Páramo, Daniel; Quiroz-Mercado, Hugo; Quintanar-Stéphano, Andrés; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2010-01-01

    OBJECTIVE Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for the development of sight-threatening proliferative diabetic retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR. Here, we investigate the circulating levels of PRL in association with DR in men and test whether increased circulating PRL, by serving as a source of ocular vasoinhibins, can reduce the pathological RVP in diabetes. RESEARCH DESIGN AND METHODS Serum PRL was evaluated in 40 nondiabetic and 181 diabetic men at various stages of DR. Retinal vasoinhibins were measured in rats rendered hyperprolactinemic by placing two anterior pituitary grafts under the kidney capsule and in PRL receptor–null mice. RVP was determined in hyperprolactinemic rats subjected to the intraocular injection of vascular endothelial growth factor (VEGF) or made diabetic with streptozotocin. RESULTS The circulating levels of PRL increased in diabetes and were higher in diabetic patients without retinopathy than in those with proliferative DR. In rodents, hyperprolactinemia led to vasoinhibin accumulation within the retina; genetic deletion of the PRL receptor prevented this effect, indicating receptor-mediated incorporation of systemic PRL into the eye. Hyperprolactinemia reduced both VEGF-induced and diabetes-induced increase of RVP. This reduction was blocked by bromocriptine, an inhibitor of pituitary PRL secretion, which lowers the levels of circulating PRL and retinal vasoinhibins. CONCLUSIONS Circulating PRL influences the progression of DR after its intraocular conversion to vasoinhibins. Inducing hyperprolactinemia may represent a novel therapy against DR. PMID:20823101

  13. Automatic recognition of severity level for diagnosis of diabetic retinopathy using deep visual features.

    PubMed

    Abbas, Qaisar; Fondon, Irene; Sarmiento, Auxiliadora; Jiménez, Soledad; Alemany, Pedro

    2017-03-28

    Diabetic retinopathy (DR) is leading cause of blindness among diabetic patients. Recognition of severity level is required by ophthalmologists to early detect and diagnose the DR. However, it is a challenging task for both medical experts and computer-aided diagnosis systems due to requiring extensive domain expert knowledge. In this article, a novel automatic recognition system for the five severity level of diabetic retinopathy (SLDR) is developed without performing any pre- and post-processing steps on retinal fundus images through learning of deep visual features (DVFs). These DVF features are extracted from each image by using color dense in scale-invariant and gradient location-orientation histogram techniques. To learn these DVF features, a semi-supervised multilayer deep-learning algorithm is utilized along with a new compressed layer and fine-tuning steps. This SLDR system was evaluated and compared with state-of-the-art techniques using the measures of sensitivity (SE), specificity (SP) and area under the receiving operating curves (AUC). On 750 fundus images (150 per category), the SE of 92.18%, SP of 94.50% and AUC of 0.924 values were obtained on average. These results demonstrate that the SLDR system is appropriate for early detection of DR and provide an effective treatment for prediction type of diabetes.

  14. Activation of Melanocortin Receptors MC 1 and MC 5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy.

    PubMed

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

    2016-01-01

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

  15. Telemedicine screening of diabetic retinopathy using a hand-held fundus camera.

    PubMed

    Yogesan, K; Constable, I J; Barry, C J; Eikelboom, R H; McAllister, I L; Tay-Kearney, M L

    2000-01-01

    The objective was to evaluate digital images of the retina from a handheld fundus camera (Nidek NM-100) for suitability in telemedicine screening of diabetic retinopathy. A handheld fundus camera (Nidek) and a standard fundus camera (Zeiss) were used to photograph 49 eyes from 25 consecutive patients attending our diabetic clinic. One patient had cataracts, making it impossible to get a quality image of one of the eyes (retina). The Nidek images were digitized, compressed, and stored in a Fujix DF-10M digitizer supplied with the camera. The digital images and the photographs were presented separately in a random order to three ophthalmologists. The quality of the images was ranked as good, acceptable or unacceptable for diabetic retinopathy diagnosis. The images were also evaluated for the presence of microaneurysms, blot hemorrhages, exudates, fibrous tissue, previous photocoagulation, and new vessel formation. kappa Values were computed for agreement between the photographs and digital images. Overall agreement between the photographs and digital images was poor (kappa < 0.30). On average, only 24% of the digital images were graded as being good quality and 56% as having an acceptable quality. However, 93% of the photographs were graded as good-quality images for diagnosis. The results indicate that the digital images from the handheld fundus camera may not be suitable for diagnosis of diabetic retinopathy. The images shown on the liquid crystal display (LCD) screen of the camera were of good quality. However, the images produced by the digitizer (Fujix DF-10M) attached to the camera were not as good as the images shown on the LCD screen. A better digitizing system may produce better quality images from the Nidek camera.

  16. Retinopathy Signs Improved Prediction and Reclassification of Cardiovascular Disease Risk in Diabetes: A prospective cohort study

    PubMed Central

    Ho, Henrietta; Cheung, Carol Y.; Sabanayagam, Charumathi; Yip, Wanfen; Ikram, Mohammad Kamran; Ong, Peng Guan; Mitchell, Paul; Chow, Khuan Yew; Cheng, Ching Yu; Tai, E. Shyong; Wong, Tien Yin

    2017-01-01

    CVD risk prediction in diabetics is imperfect, as risk models are derived mainly from the general population. We investigate whether the addition of retinopathy and retinal vascular caliber improve CVD prediction beyond established risk factors in persons with diabetes. We recruited participants from the Singapore Malay Eye Study (SiMES, 2004–2006) and Singapore Prospective Study Program (SP2, 2004–2007), diagnosed with diabetes but no known history of CVD at baseline. Retinopathy and retinal vascular (arteriolar and venular) caliber measurements were added to risk prediction models derived from Cox regression model that included established CVD risk factors and serum biomarkers in SiMES, and validated this internally and externally in SP2. We found that the addition of retinal parameters improved discrimination compared to the addition of biochemical markers of estimated glomerular filtration rate (eGFR) and high-sensitivity C-reactive protein (hsCRP). This was even better when the retinal parameters and biomarkers were used in combination (C statistic 0.721 to 0.774, p = 0.013), showing improved discrimination, and overall reclassification (NRI = 17.0%, p = 0.004). External validation was consistent (C-statistics from 0.763 to 0.813, p = 0.045; NRI = 19.11%, p = 0.036). Our findings show that in persons with diabetes, retinopathy and retinal microvascular parameters add significant incremental value in reclassifying CVD risk, beyond established risk factors. PMID:28148953

  17. BARRIERS TO AN EFFECTIVE DIABETIC RETINOPATHY SERVICE IN IBADAN, NIGERIA (SUB -SAHARAN AFRICA) - A PILOT QUALITATIVE STUDY

    PubMed Central

    Ibrahim, O.A.; Foster, A.; Oluleye, T.S.

    2015-01-01

    Background: Diabetic retinopathy is an increasing cause of blindness. The prevalence of retinopathy in hospital attending diabetics in Ibadan is reported to be 42 %. This study assessed the barriers identified by patients and service providers to delivering good services for diabetic retinopathy in Ibadan, Nigeria, Sub-Saharan Africa. Methods: A qualitative survey using non-participatory observation, in-depth interviews (patients and healthcare providers), and focus group discussion for diabetic patients in the eye clinic in University College Hospital, Ibadan was done. Semistructured interview and topic guides were used to evaluate the barriers to effective service. The participants were selected using a non-probability, purposive sampling strategy. Twenty participants were involved in the pilot study. There were ten in-depth interviews of patients and two focus group discussions of patients (3 in each group). Four healthcare providers were interviewed (a retinal surgeon, a senior registrar, an endocrinologist and a public health nurse). Results: Lack of awareness that diabetes causes irreversible blindness was identified as a major barrier by both patients and providers. Cost of treatment of diabetes and treatment of retinopathy was also an important barrier. The long waiting time before consultation, staff attitudes to patients and appointment scheduling problems deterred patients from using the service. Conclusions: More diabetic patients can be encouraged to use eye service by providing more detailed information/counselling and making clinic attendance less costly and more convenient. PMID:26807085

  18. Dietary taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in streptozotocin-induced Sprague-Dawley rats.

    PubMed

    Yu, Xiaoping; Xu, Zhaoxia; Mi, Mantian; Xu, Hongxia; Zhu, Jundong; Wei, Na; Chen, Ka; Zhang, Qianyong; Zeng, Kaihong; Wang, Jian; Chen, Fang; Tang, Yong

    2008-03-01

    The purpose of this study was to investigate whether taurine ameliorate the diabetic retinopathy, and to further explore the underlying mechanisms. The Sprague-Dawley rats were injected with streptozotocin to establish experimental diabetic model, then fed without or with 1.2% taurine for additional 4-12 weeks. After that, the protective effects of dietary taurine supplementation on diabetic retinopathy were estimated. Our results showed that chronic taurine supplement effectively improved diabetic retinopathy as changes of histopathology and ultrastructure. The supplementation could not lower plasma glucose concentration (P > 0.05), but caused an elevation in taurine content and a decline in levels of glutamate and gamma-aminobutyric acid (GABA) in diabetic retina (P < 0.05). Moreover, chronic taurine supplementation increased glutamate transporter (GLAST) expression (P < 0.05), decreased intermediate filament glial fibrillary acidic protein (GFAP) and N-methyl-D: -aspartate receptor subunit 1 (NR1) expression in diabetic retina (P < 0.05). These results demonstrated that chronic taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in rats.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Ramsey, David J; Arden, G B

    2015-12-01

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

  1. A modified matched filter with double-sided thresholding for screening proliferative diabetic retinopathy.

    PubMed

    Zhang, Lei; Li, Qin; You, Jane; Zhang, David

    2009-07-01

    The early diagnosis of proliferative diabetic retinopathy (PDR), a common complication of diabetes that damages the retina, is crucial to the protection of the vision of diabetes sufferers. The onset of PDR is signaled by the appearance of neovascular net. Such neovascular nets might be identified using retinal vessel extraction techniques. The commonly used matched filter methods often produce false positive detections of neovascular nets due to their proneness to detect nonline edges as well as lines. In this paper, we propose a modified matched filter for retinal vessel extraction that applies a local vessel cross-section analysis using double-sided thresholding to reduce false responses to nonline edges. Our proposed modified matched filters demonstrated higher true positive rate and lesser false detection than existing matched-filter-based schemes in vessel extraction.

  2. [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.

  3. 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

  4. 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

  5. Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R)

    PubMed Central

    Gunnlaugsdottir, E.; Halldorsdottir, S.; Klein, R.; Eiriksdottir, G.; Klein, B. E.; Benediktsson, R.; Harris, T. B.; Launer, L. J.; Aspelund, T.; Gudnason, V.

    2012-01-01

    Aims/hypothesis We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. Methods The study population consisted of 4,994 persons aged ≥67 years, who participated in the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA1c ≥6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. Results The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA1c, insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Conclusions/interpretation Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged. PMID:22134840

  6. Prevalence and Cardiovascular Associations of Diabetic Retinopathy and Maculopathy: Results from the Gutenberg Health Study

    PubMed Central

    Raum, Philipp; Lamparter, Julia; Ponto, Katharina A.; Peto, Tunde; Hoehn, René; Schulz, Andreas; Schneider, Astrid; Wild, Philipp S.; Pfeiffer, Norbert; Mirshahi, Alireza

    2015-01-01

    Objective Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany. Research Design and Methods The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases. Results Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955–0.992]; p = 0.006) arterial hypertension (1.90 [1.190–3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504–7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068–1.114]; p<0.0001 and 1.18 [1.137–1.222]; p<0.0001, respectively). Conclusions Our calculations suggest that more than a quarter-million persons have vision-threatening diabetic retinal disease in Germany. Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus. PMID:26075604

  7. 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

  8. Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy.

    PubMed

    Yun, Jang-Hyuk; Park, Sung Wook; Kim, Kyung-Jin; Bae, Jong-Sup; Lee, Eun Hui; Paek, Sun Ha; Kim, Seung U; Ye, Sangkyu; Kim, Jeong-Hun; Cho, Chung-Hyun

    2017-05-01

    Vascular inflammation is characteristic feature of diabetic retinopathy. In diabetic retina, a variety of the pro-inflammatory cytokines are elevated and involved in endothelial dysfunction. STAT3 transcription factor has been implicated in mediating cytokine signaling during vascular inflammation. However, whether and how STAT3 is involved in the direct regulation of the endothelial permeability is currently undefined. Our studies revealed that IL-6-induced STAT3 activation increases retinal endothelial permeability and vascular leakage in retinas of mice through the reduced expression of the tight junction proteins ZO-1 and occludin. In a co-culture model with microglia and endothelial cells under a high glucose condition, the microglia-derived IL-6 induced STAT3 activation in the retinal endothelial cells, leading to increasing endothelial permeability. In addition, IL-6-induced STAT3 activation was independent of ROS generation in the retinal endothelial cells. Moreover, we demonstrated that STAT3 activation downregulates the ZO-1 and occludin levels and increases the endothelial permeability through the induction of VEGF production in retinal endothelial cells. These results suggest the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. J. Cell. Physiol. 232: 1123-1134, 2017. © 2016 Wiley Periodicals, Inc.

  9. 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

  10. 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

  11. Inhibition of Stat3 by a Small Molecule Inhibitor Slows Vision Loss in a Rat Model of Diabetic Retinopathy

    PubMed Central

    Vanlandingham, Phillip A.; Nuno, Didier J.; Quiambao, Alexander B.; Phelps, Eric; Wassel, Ronald A.; Ma, Jian-Xing; Farjo, Krysten M.; Farjo, Rafal A.

    2017-01-01

    Purpose Diabetic retinopathy is a leading cause of vision loss. Previous studies have shown signaling pathways mediated by Stat3 (signal transducer and activator of transcription 3) play a primary role in diabetic retinopathy progression. This study tested CLT-005, a small molecule inhibitor of Stat3, for its dose-dependent therapeutic effects on vision loss in a rat model of diabetic retinopathy. Methods Brown Norway rats were administered streptozotocin (STZ) to induce diabetes. CLT-005 was administered daily by oral gavage for 16 weeks at concentrations of 125, 250, or 500 mg/kg, respectively, beginning 4 days post streptozotocin administration. Systemic and ocular drug concentration was quantified with mass spectrometry. Visual function was monitored at 2-week intervals from 6 to 16 weeks using optokinetic tracking to measure visual acuity and contrast sensitivity. The presence and severity of cataracts was visually monitored and correlated to visual acuity. The transcription and translation of multiple angiogenic factors and inflammatory cytokines were measured by real-time polymerase chain reaction and Multiplex immunoassay. Results Streptozotocin-diabetic rats sustain progressive vision loss over 16 weeks, and this loss in visual function is rescued in a dose-dependent manner by CLT-005. This positive therapeutic effect correlates to the positive effects of CLT-005 on vascular leakage and the presence of inflammatory cytokines in the retina. Conclusions The present study indicates that Stat3 inhibition has strong therapeutic potential for the treatment of vision loss in diabetic retinopathy. PMID:28395025

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

    PubMed Central

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

    2012-01-01

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

  13. Animal models of diabetic retinopathy: doors to investigate pathogenesis and potential therapeutics.

    PubMed

    Jo, Dong Hyun; Cho, Chang Sik; Kim, Jin Hyoung; Jun, Hyoung Oh; Kim, Jeong Hun

    2013-06-20

    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.

  14. [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.

  15. 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.

  16. 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.

  17. 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.

  18. [Role of vascular endothelial growth factor and monocyte chemoattractant protein-1 in the development of endothelial dysfunction in types 1 and 2 diabetes mellitus complicated by diabetic retinopathy].

    PubMed

    Nikitina, V V; Zakharova, N B; Kamenskikh, T G

    2011-06-01

    The paper presents the results of a study of the serum levels of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) in 120 patients with types 1 and 2 diabetes mellitus complicated by diabetic retinopathy. All the patients with diabetes have been ascertained to show a rise in the levels of MCP-1 and VEGF. Calculation of VEGF/MCP-1 ratio is proposed to evaluate vascular bed lesion in diabetic patients.

  19. 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

  20. Prediction of risk of diabetic retinopathy for all-cause mortality, stroke and heart failure

    PubMed Central

    Zhu, Xiao-Rong; Zhang, Yong-Peng; Bai, Lu; Zhang, Xue-Lian; Zhou, Jian-Bo; Yang, Jin-Kui

    2017-01-01

    Abstract To examine and quantify the potential relation between diabetic retinopathy (DR) and risk of all-cause mortality, stroke and heart failure (HF). The resources of meta-analysis of epidemiological observational studies were from Pub-med, EMBASE, CINAHL, Cochrane Library, conference, and proceedings. Random/fixed effects models were used to calculate pooled subgroup analysis stratified by different grades of DR was performed to explore the potential source of heterogeneity. Statistical manipulations were undertaken using program STATA. Of the included 25 studies, comprising 142,625 participants, 19 studies were concluded to find the relation of DR to all-cause mortality, 5 for stroke, and 3 for HF. Risk ratio (RR) for all-cause mortality with the presence of DR was 2.33 (95% CI 1.92–2.81) compared with diabetic individuals without DR. Evidences showed a higher risk of all-cause mortality associated with DR in patients with T2D or T1D (RR 2.25, 95% CI 1.91–2.65. RR 2.68, 95% CI 1.34–5.36). According to different grades of DR in patients with T2D, RR for all-cause mortality varied, the risk of nonproliferative diabetic retinopathy (NPDR) was 1.38 (1.11–1.70), while the risk of proliferative diabetic retinopathy (PDR) was 2.32 (1.75–3.06). There was no evidence of significant heterogeneity (Cochran Q test P = 0.29 vs 0.26, I2 = 19.6% vs 22.6%, respectively). Data from 5 studies in relation to DR and the risk of stroke showed that DR was significantly associated with increased risk of stroke (RR = 1.74, 95%CI: 1.35–2.24), compared with patients without DR. Furthermore, DR (as compared with individuals without DR) was associated with a marginal increased risk of HF in patients with diabetes mellitus (DM) (n = 3 studies; RR 2.24, 95% CI 0.98–5.14, P = 0.056). Our results showed that DR increased the risk of all-cause mortality, regardless of the different stages, compared with the diabetic individuals without DR. DR predicted

  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. Organotypic retinal explant cultures as in vitro alternative for diabetic retinopathy studies.

    PubMed

    Valdés, Joaquín; Trachsel-Moncho, Laura; Sahaboglu, Ayse; Trifunović, Dragana; Miranda, María; Ueffing, Marius; Paquet-Durand, François; Schmachtenberg, Oliver

    2016-01-01

    Diabetic retinopathy (DR) is a major cause of vision loss and one of the most common and debilitating complications of diabetes. Research to prevent DR is hindered by a lack of experimental model systems that faithfully reproduce the disease pathology, in particular for type 2 diabetes, which requires prolonged disease progression in animals to develop some hallmarks of DR. Here, we introduce an alternative in vitro model system for DR, based on serum-free, organotypic rodent retinal explant cultures, which allow physiological and pharmacological manipulation of the retina for up to two weeks under tightly controlled conditions. Retinal explant cultures have the advantage of isolating direct neuronal consequences of diabetic conditions from indirect systemic effects mediated via the retinal vasculature or the immune system. Exposed to conditions emulating type 1 or type 2 diabetes, retinal explants displayed elevated cell death rates among inner retinal neurons as well as photoreceptors, with a particularly strong loss of cone photoreceptors. Our results support a direct impact of diabetic conditions on retinal neurons and may help explain color vision defects observed in DR patients. This serum-free in vitro DR model avoids the animal suffering of established DR models and reduces the overall number of animals needed for such research. It should prove useful to study the mechanisms of neuronal cell death caused by DR and to screen for potential future DR treatments.

  3. 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

  4. Changes in Frequency-Doubling Perimetry in Patients with Type I Diabetes prior to Retinopathy

    PubMed Central

    Pinilla, Isabel; Ferreras, Antonio; Idoipe, Miriam; Sanchez-Cano, Ana I.; Perez-Garcia, Diana; Herrera, Laura X.; Pinilla, Maria J.

    2013-01-01

    Purpose. To evaluate the ability of frequency-doubling technology (FDT) perimetry in detecting visual field defects in young adults with type I diabetes prior to retinopathy or with minor retinovascular changes. Methods. This comparative cross-sectional study included 30 healthy subjects and 73 age-matched patients with type I diabetes mellitus. All subjects underwent a full ocular examination including an FDT with the threshold C-20-5 strategy. Only one eye per subject was randomly included in the statistical analysis. FDT results and time to perform the test were compared between the groups. Results. The mean age was 27.1 years in the control group and 26.6 years in the diabetic group (P = 0.875). The mean period from the onset of diabetes was 12.6 ± 6.7 years, while minimal retinovascular changes were observed in 18 eyes. Mean deviation of FDT did not differ between the groups. Although global indices of FDT were within normal limits, pattern standard deviation of FDT was higher in the diabetic group (P = 0.035). The area under the receiver operating characteristic curve was 0.647 for pattern standard deviation of FDT (standard error = 0.052; P = 0.017). Conclusion. FDT can detect retinal dysfunctions in diabetic patients prior to the onset of significant vascular complications. PMID:24319681

  5. [Effectiveness of bio-regulators in the treatment of diabetic retinopathy].

    PubMed

    Trofimova, S V; Khavinson, V Kh

    2001-01-01

    Treatment of diabetic retinopathy remains a most important problem of modern ophthalmology. Bioregulatory therapy has been widely used in recent years as one of promising trends in clinical medicine. The purpose of this study was to evaluate the efficiency of peptide bioregulators in combined treatment of diabetic retinopathy. A total of 104 patients were administered bioregulatory therapy (retinal preparation retinalamine, epiphysis preparation epithalamine, cerebral cortex preparation cortexine,) and 42 patients were controls. Peptide bioregulators in 90% cases promoted improvement of vision acuity, improved the ophthalmoscopic picture of the fundus oculi (resolution of hemorrhages, plasmorrhages, decreased macular edema) and in all cases improved the functional activity of the retina and retinal bloodflow. No negative changes in the clinical picture were observed after peptide bioregulators in any of the cases. Peptide bioregulators normalized carbohydrate metabolism (sugar level and glycosylated hemoglobin in the blood), phagocytosis, and improved the subjective well-being of patients. Hence, the data indicate a pathogenetic effect of this therapeutic method and its good prospects in ophthalmology.

  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.

  7. Micro RNA-19a suppresses interleukin-10 in peripheral B cells of patients with diabetic retinopathy

    PubMed Central

    Wang, Cong; You, Qisheng; Cao, Xusheng; Guo, Huiling; Gao, Xinxiao; Peng, Xiaoyan

    2017-01-01

    A number of patients with diabetes suffer from retinopathy; the pathogenesis is to be further investigated. Recent reports indicate that micro RNA (miR) plays critical roles in the development of immune inflammation. This study test a hypothesis that miR-17-92 cluster is associated with the pathogenesis of diabetes retinopathy (DR). In this study, peripheral blood samples were collected from DR patients and healthy subjects. B cells were isolated from the blood samples to be analyzed the expression of interleukin (IL)-10. The results showed that lower levels of IL-10 were detected in peripheral B cells of DR patients as compared with healthy subjects. miR-19a was increased in B cells of DR patients, which was negatively correlated with the IL-10 expression. Exposure of naive B cells to IL-17 increased the expression of miR-19a and suppression of IL-10 expression in the B cells, in which histone deacetylase 11 (HDAC 11) played a critical role. In conclusion, the IL-17 suppresses IL-10 expression in peripheral B cells via enhancing miR-19a expression and HDAC activity in DR patients. The miR-19a and HDAC 11 may be novel therapeutic targets in the treatment of DR. PMID:28386366

  8. 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.

  9. 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

  10. Ultra-wide field retinal imaging in detection, classification, and management of diabetic retinopathy.

    PubMed

    Soliman, Ahmed Z; Silva, Paolo S; Aiello, Lloyd Paul; Sun, Jennifer K

    2012-01-01

    Current ultra-wide field (UWF) retinal imaging systems utilize scanning laser ophthalmoscope technology combined with an ellipsoidal mirror to capture up to 200 degrees of the retina in a single image. When compared with mydriatic ETDRS-protocol, 7 standard field photographs and clinical examination, nonmydriatic UWF images appear to have excellent agreement in allowing the detection and classification of diabetic retinopathy (DR), although larger, definitive validation studies are still forthcoming. UWF imaging and angiography allow visualization of peripheral retinal nonperfusion, vascular leakage and neovascularization in patients with DR that may not be captured on 7 standard fields. Prospective randomized controlled trials are needed to evaluate whether modified laser treatment algorithms based on improved visualization of the retinal periphery might improve patient outcomes. Nonmydriatic UWF imaging has potential applications for ocular diabetic telehealth programs, but validation of newer, more portable, and more affordable UWF imaging models is needed.

  11. 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

  12. Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser

    PubMed Central

    Oshima, Y.; Emi, K.; Yamanishi, S.; Motokura, M.

    1999-01-01

    AIMS—To evaluate the scanning retinal thickness analyser (RTA), a novel non-invasive imaging instrument, in diagnosing and quantitatively characterising diabetic macular oedema, and to investigate the relation between central macula thickness measured by RTA and other clinical examinations.
METHODS—Central macular thickness was measured using the RTA in 40 normal subjects and 60 patients with diabetic retinopathy. The reproducibility of the retinal thickness measurements was evaluated by calculating the mean of the inter- and intrasession variations. Central macular thickness was correlated with the results of visual acuity measurements, biomicroscopy, and fluorescein angiography.
RESULTS—Intra- and intersession reproducibility of the RTA in normal subjects was plus or minus 5.2% (16 µm) and plus or minus 6.1% (19 µm), respectively. The mean central macular thickness was 182 (SD 16) µm in normal subjects, 283 (116) µm in diabetic eyes without clinically significant macular oedema (CSMO), and 564 (168) µm in diabetic eyes with CSMO. Central macular thickness was significantly greater (p<0.001) in eyes with diabetic retinopathy than in normal subjects, even when macular thickening did not meet the standard for CSMO (p=0.019) measured by biomicroscopy. Although greater fluorescein leakage at the macula results in greater central macular thickness, only eyes with diffuse leakage had statistically significant macular thickening compared with normal subjects (p=0.022). Central macular thickness measured with the RTA was significantly correlated with the logarithmic converted visual acuity (r2= 0.76) in diabetic eyes.
CONCLUSION—Scanning RTA, which has good reproducibility, might be useful to quantitatively detect and monitor macular thickening in diabetic retinopathy. Central macular thickness was highly correlated with logarithmic converted visual acuity in diabetic macular oedema.

 Keywords: scanning retinal thickness analyser; macular

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

    PubMed Central

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

    2016-01-01

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

  15. Relationship between C-Reactive Protein Level and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Song; Duan, Hongtao; Kong, Jiahui; Li, Zedong

    2015-01-01

    Objectives To date, the relationship between C-reactive protein (CRP) level and diabetic retinopathy (DR) remains controversial. Therefore, a systematic review and meta-analysis was used to reveal the potential relationship between CRP level and DR. Methods A systematic search of PubMed, Embase.com, and Web of Science was performed to identify all comparative studies that compared the CRP level of two groups (case group and control group). We defined that diabetic patients without retinopathy and /or matched healthy persons constituted the control group, and patients with DR were the case group. Results Two cross sectional studies and twenty case control studies including a total of 3679 participants were identified. After pooling the data from all 22 studies, obvious heterogeneity existed between the studies, so a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the blood CRP levels in the case group were observed to be higher than those in the control group [SMD = 0.22, 95% confidence interval (CI), 0.11–0.34], and the blood CRP levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group [SMD = 0.50, 95% CI, 0.30–0.70]. Conclusions The results from this current meta-analysis indicate that the CRP level might be used as a biomarker to determine the severity of DR. PMID:26636823

  16. Neurodegeneration in the Pathogenesis of Diabetic Retinopathy: Molecular Mechanisms and Therapeutic Implications

    PubMed Central

    Stem, Maxwell S.; Gardner, Thomas W.

    2014-01-01

    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 complications 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 neural apoptosis 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 might 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

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

    PubMed Central

    Khandekar, Rajiv

    2012-01-01

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

  18. 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

  19. Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy

    PubMed Central

    Arima, Mitsuru; Cui, Dan; Kimura, Tokuhiro; Sonoda, Koh-Hei; Ishibashi, Tatsuro; Matsuda, Satoshi; Ikeda, Eiji

    2016-01-01

    Despite the advance in medical technology, diabetic retinopathy (DR) is still an intractable disease which leads to the damage of retinal cells and finally the visual loss. Impairment of retinal vascular barrier triggered by an admixture of multiple inflammatory cytokines is a core of pathophysiology of DR. Therefore, the molecules involved commonly in multiple cytokines-induced impairment of vascular barrier would be the targets of curative treatment of DR. Here, we demonstrate that basigin, a transmembrane molecule expressed in neural barrier-forming endothelial cells, is the molecule essential for vascular barrier impairment which is shared by various triggers including VEGF, TNFα and IL-1β. In vitro data with neural microvascular endothelial cells indicated that stimulation with cytokines decreases the levels of claudin-5 in cell membranes and consequently impairs the barrier function in a manner dependent on the interaction of claudin-5 with basigin and caveolin-1. In addition, the increased vascular permeability in retinas of streptozotocin-induced diabetic mice was shown to be clearly normalized by intravitreous injection of siRNAs specific for basigin. This study has highlighted basigin as a common essential molecule for various stimuli-induced impairment of retinal vascular barrier, which can be a target for strategies to establish a curative treatment of DR. PMID:27917946

  20. United Kingdom National Ophthalmology Database Study: Diabetic Retinopathy; Report 1: prevalence of centre-involving diabetic macular oedema and other grades of maculopathy and retinopathy in hospital eye services

    PubMed Central

    Keenan, T D L; Johnston, R L; Donachie, P H J; Sparrow, J M; Stratton, I M; Scanlon, P

    2013-01-01

    Aims To report estimates of the prevalence of diabetic retinopathy (DR) and maculopathy grades for a large cohort of patients managed by the UK hospital eye service (HES). Methods Anonymised data were extracted from 30 UK NHS hospital trusts using a single ophthalmic electronic medical record (EMR) for the period from April 2000 to November 2010 to create the National Ophthalmology Database (NOD). From 2007, the EMR facilitated capture of a nationally agreed-upon standardised data set (DR Structured Assessment) relating to the presence or absence of clinical signs of DR and maculopathy. An algorithm in the software automatically calculated the Early Treatment of Diabetic Retinopathy Study grades of retinopathy and maculopathy. Results Between 2007 and 2010, 307 538 patients had data on the NOD, with 76 127 (24.8%) patients having been recorded as having diabetes. The proportion of patients with diabetes who had a structured assessment increased from 50.7% (2007) to 86.8% (2010). In each NHS year, 12.6–20.6% of eyes with structured assessments had no DR; 59.6–67.3% had non-proliferative DR; and 18.3–20.9% had active or regressed proliferative DR. Clinically significant macular oedema was present in 15.8–18.1% of eyes, and in 8.7–10.0% of eyes, this involved the central macula. Conclusion This study provides contemporary estimates of the prevalence of retinopathy and maculopathy grades in a large cohort of patients with diabetes managed by the UK HES. Centre-involving diabetic macular oedema, potentially amenable to anti-VEGF therapy, is present in the eyes of almost 10% of these patients. This information is useful for clinicians, health-care economists, and commissioners involved in planning and delivering diabetic eye services. PMID:24051410

  1. New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes

    DTIC Science & Technology

    2005-11-01

    who do not. The 3 major complications to be evaluated are diabetic nephropathy , diabetic neuropathy, and diabetic retinopathy. This is an...families for diabetic nephropathy , autonomic neuropathy, and retinopathy. Body The title of this study is “Genetic Screening in Diabetes .” This is an...susceptibility and/or development of diabetic nephropathy , neuropathy, and retinopathy. It is expected that WRAMC will enroll up to 100 probands and

  2. 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.

  3. The Negative Relationship between Bilirubin Level and Diabetic Retinopathy: A Meta-Analysis

    PubMed Central

    Wu, Xiaomei; Ning, Kang; Jiang, Feng; Zhang, Lu

    2016-01-01

    Objectives Findings on the relationship between total bilirubin level (TBL) and diabetic retinopathy (DR) are inconsistent. Thus, we carried out a meta-analysis to investigate the relationship between TBL and the risk of DR. Methods Relevant studies were selected from six databases up to 31 May 2016 using a search strategy. The relevant data were extracted from the included studies according to the inclusion and exclusion criteria, and the mean value with standard errors or odds ratio (OR) with 95% confidence intervals (CIs) were calculated. We compared TBL in patients with DR with that in patients with diabetes but without retinopathy (NDR), and analyzed the dose-response relationship between TBL and the risk of DR. Results Twenty-four studies were selected in this meta-analysis. Twenty studies were included to calculate the pooled SMD, and the results showed that TBL in the DR group was lower than that in the NDR group (SMD: –0.52, 95% CI: –0.67, –0.38). Nine studies were included to calculate the pooled ORs, and the results showed that there was a significant negative relationship between TBL and the risk of DR (OR: 0.19, 95% CI: 0.14, 0.25). Six studies were included to investigate the dose-response relationship between TBL and the risk of DR, and we found a nonlinear relationship between TBL and the risk of DR. The results of our meta-analysis were found to be reliable using subgroup and sensitivity analyses. Conclusions The results of our meta-analysis indicate that higher TBL may be protective against DR in subjects with diabetes, and TBL could be used as a biomarker to predict the risk of DR. PMID:27571522

  4. 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.

  5. Renal Function but Not Asymmetric Dimethylarginine Is Independently Associated with Retinopathy in Type 2 Diabetes

    PubMed Central

    Krzyzanowska, Katarzyna; Mittermayer, Friedrich; Schernthaner, Gerit H.; Brunner, Simon; Brix, Johanna M.; Aschauer, Stefan; Höllerl, Florian; Wolzt, Michael; Schernthaner, Guntram

    2011-01-01

    Background. Asymmetric dimethylarginine (ADMA) is associated with macrovascular disease and possibly with microangiopathy in type 2 diabetes (T2DM). We tested the hypothesis that ADMA is related to diabetic retinopathy (DR) independently of macrovascular disease. Methods. This cross-sectional study included 127 T2DM patients selected to achieve equal distributions of patients with and without macrovascular disease in the groups with and without DR. Results. Patients with DR had increased ADMA, longer diabetes duration, and reduced glomerular filtration rate (GFR). ADMA correlated with GFR (ρ = -0.35; P < .001), diabetes duration (ρ = 0.19; P = .048), and age (ρ = 0.19; P = .033). Logistic regression analysis revealed an association of ADMA with DR. After adjustment for macrovascular disease, this association remained significant (OR 1.48; 95% CI: 1.02–2.15; P = .039). Inclusion of GFR and T2DM duration into the model abolished this significant relationship. GFR remained the only independent predictor for DR. A 10 mL/min/1.73 m2 GFR decrease was associated with DR in a multivariate model (OR 1.30; 95% CI: 1.08–1.56; P = .006). Conclusions. These findings indicate an association between ADMA and DR in T2DM independent of macrovascular disease. This relationship is modified by GFR, the only parameter significantly related to DR in multivariate analysis. PMID:21629851

  6. Renal function but not asymmetric dimethylarginine is independently associated with retinopathy in type 2 diabetes.

    PubMed

    Krzyzanowska, Katarzyna; Mittermayer, Friedrich; Schernthaner, Gerit H; Brunner, Simon; Brix, Johanna M; Aschauer, Stefan; Höllerl, Florian; Wolzt, Michael; Schernthaner, Guntram

    2011-01-01

    Background. Asymmetric dimethylarginine (ADMA) is associated with macrovascular disease and possibly with microangiopathy in type 2 diabetes (T2DM). We tested the hypothesis that ADMA is related to diabetic retinopathy (DR) independently of macrovascular disease. Methods. This cross-sectional study included 127 T2DM patients selected to achieve equal distributions of patients with and without macrovascular disease in the groups with and without DR. Results. Patients with DR had increased ADMA, longer diabetes duration, and reduced glomerular filtration rate (GFR). ADMA correlated with GFR (ρ = -0.35; P < .001), diabetes duration (ρ = 0.19; P = .048), and age (ρ = 0.19; P = .033). Logistic regression analysis revealed an association of ADMA with DR. After adjustment for macrovascular disease, this association remained significant (OR 1.48; 95% CI: 1.02-2.15; P = .039). Inclusion of GFR and T2DM duration into the model abolished this significant relationship. GFR remained the only independent predictor for DR. A 10 mL/min/1.73 m(2) GFR decrease was associated with DR in a multivariate model (OR 1.30; 95% CI: 1.08-1.56; P = .006). Conclusions. These findings indicate an association between ADMA and DR in T2DM independent of macrovascular disease. This relationship is modified by GFR, the only parameter significantly related to DR in multivariate analysis.

  7. 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

  8. Constructing Benchmark Databases and Protocols for Medical Image Analysis: Diabetic Retinopathy

    PubMed Central

    Kauppi, Tomi; Kämäräinen, Joni-Kristian; Kalesnykiene, Valentina; Sorri, Iiris; Uusitalo, Hannu; Kälviäinen, Heikki

    2013-01-01

    We address the performance evaluation practices for developing medical image analysis methods, in particular, how to establish and share databases of medical images with verified ground truth and solid evaluation protocols. Such databases support the development of better algorithms, execution of profound method comparisons, and, consequently, technology transfer from research laboratories to clinical practice. For this purpose, we propose a framework consisting of reusable methods and tools for the laborious task of constructing a benchmark database. We provide a software tool for medical image annotation helping to collect class label, spatial span, and expert's confidence on lesions and a method to appropriately combine the manual segmentations from multiple experts. The tool and all necessary functionality for method evaluation are provided as public software packages. As a case study, we utilized the framework and tools to establish the DiaRetDB1 V2.1 database for benchmarking diabetic retinopathy detection algorithms. The database contains a set of retinal images, ground truth based on information from multiple experts, and a baseline algorithm for the detection of retinopathy lesions. PMID:23956787

  9. 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

  10. 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.

  11. Influencing factors on compliance of timely visits among patients with proliferative diabetic retinopathy in southern China: a qualitative study

    PubMed Central

    Duan, Fang; Liu, Yuhong; Chen, Xiang; Congdon, Nathan; Zhang, Jian; Chen, Qianyun; Chen, Lingling; Chen, Xi; Zhang, Xiulan; Yu, Chengpu; Liu, Yizhi

    2017-01-01

    Objective To identify the reasons for low adherence among patients with diabetic retinopathy (DR) in southern China using a qualitative method. Methods Exploratory indepth interviews were conducted in 27 diabetic patients with proliferative diabetic retinopathy who required vitrectomy surgery at Zhongshan Ophthalmic Centre, Sun Yat-sen University, from March to August 2015. Qualitative data analysis and research software (ATLAS.ti7) was used for data processing and analysis. Results Factors influencing the occurrence of timely visits included lack of DR related knowledge, fear and worries about insulin, interactions between patients and society combined with the complexity of emotions and social culture, and the economic burden of treatment. Conclusions Although the reasons for low adherence involved social, emotional, cultural and economic factors, the key issue was the lack of awareness and knowledge of DR. Our findings have several practical implications for health policymakers and programme planners in China. PMID:28348188

  12. A2A Adenosine Receptor (A2AAR) as a Therapeutic Target in Diabetic Retinopathy

    PubMed Central

    Ibrahim, Ahmed S.; El-shishtawy, Mamdouh M.; Zhang, Wenbo; Caldwell, Ruth B.; Liou, Gregory I.

    2011-01-01

    In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. A2A adenosine receptor (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in DR. Here, we evaluate the role of A2AAR and its underlying signaling in retinal complications associated with diabetes. Initial studies in wild-type mice revealed that the treatment with the A2AAR agonist resulted in marked decreases in hyperglycemia-induced retinal cell death and tumor necrosis factor (TNF)-α release. To further assess the role of A2AAR in DR, we studied the effects of A2AAR ablation on diabetes-induced retinal abnormalities. Diabetic A2AAR−/− mice had significantly more terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, TNF-α release, and intercellular adhesion molecule-1 expression compared with diabetic wild-type mice. To explore a potential mechanism by which A2AAR signaling regulates inflammation in DR, we performed additional studies using microglial cells treated with Amadori-glycated albumin, a risk factor in diabetic disorders. The results showed that activation of A2AAR attenuated Amadori-glycated albumin-induced TNF-α release in a cAMP/exchange protein directly activated by cAMP-dependent mechanism and significantly repressed the inflammatory cascade, C-Raf/extracellular signal-regulated kinase (ERK), in activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in DR and suggests that the retinal protective effect of A2AAR is mediated by abrogating the inflammatory response that occurs in microglia via interaction with C-Raf/ERK pathway. PMID:21514428

  13. Diabetic Retinopathy

    MedlinePlus

    ... Courier services use: Rockville, MD 20852) 301-451-2020 Research at NEI Office of the Scientific Director ... Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and Aging ...

  14. Dilated eye examination screening guideline compliance among patients with diabetes without a diabetic retinopathy diagnosis: the role of geographic access

    PubMed Central

    Lee, David J; Kumar, Naresh; Feuer, William J; Chou, Chiu-Fang; Rosa, Potyra R; Schiffman, Joyce C; Morante, Alexis; Aldahan, Adam; Staropoli, Patrick; Fernandez, Cristina A; Tannenbaum, Stacey L; Lam, Byron L

    2014-01-01

    Objective To estimate the prevalence of, and factors associated with, dilated eye examination guideline compliance among patients with diabetes mellitus (DM), but without diabetic retinopathy. Research design and methods Utilizing the computerized billing records database, we identified patients with International Classification of Diseases (ICD)-9 diagnoses of DM, but without any ocular diagnoses. The available medical records of patients in 2007–2008 were reviewed for demographic and ocular information, including visits through 2010 (n=200). Patients were considered guideline compliant if they returned at least every 15 months for screening. Participant street addresses were assigned latitude and longitude coordinates to assess their neighborhood socioeconomic status (using the 2000 US census data), distance to the screening facility, and public transportation access. Patients not compliant, based on the medical record review, were contacted by phone or mail and asked to complete a follow-up survey to determine if screening took place at other locations. Results The overall screening compliance rate was 31%. Patient sociodemographic characteristics, insurance status, and neighborhood socioeconomic measures were not significantly associated with compliance. However, in separate multivariable logistic regression models, those living eight or more miles from the screening facility were significantly less likely to be compliant relative to those living within eight miles (OR=0.36 (95% CI 0.14 to 0.86)), while public transit access quality was positively associated with screening compliance (1.34 (1.07 to 1.68)). Conclusions Less than one-third of patients returned for diabetic retinopathy screening at least every 15 months, with transportation challenges associated with noncompliance. Our results suggest that reducing transportation barriers or utilizing community-based screening strategies may improve compliance. PMID:25452871

  15. Foveal slope measurements in diabetic retinopathy: Can it predict development of sight-threatening retinopathy? Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS II, Report no 8)

    PubMed Central

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

    2015-01-01

    Aim: The aim was to assess the foveal slope configuration in subjects with type 2 diabetes in a population-based study. Materials and Methods: A subset of 668 subjects from Sankara Nethralaya Diabetic Retinopathy (DR) Epidemiology and Molecular Genetics Study II, a population-based study, were included in the current study. All the subjects underwent comprehensive ophthalmic evaluation including spectral domain optical coherence tomography. Foveal thickness was assessed in five central early treatment DR study quadrants from the three-dimensional scan and foveal slope was calculated in all the four quadrants. Results: Subjects with sight-threatening DR (STDR) had significantly shallow foveal slope in inferior quadrant (STDR: 7.33 ± 6.26 vs. controls: 10.31 ± 3.44; P = 0.021) when compared to controls and in superior (STDR: 7.62 ± 5.81 vs. no DR: 9.11 ± 2.82; P = 0.033), inferior (STDR: 7.33 ± 6.26 vs. no DR: 8.81 ± 2.81; P = 0.048), and temporal quadrants (STDR: 6.69 ± 5.70 vs. no DR: 7.97 ± 2.33; P = 0.030) when compared to subjects with no DR. Foveal slope was significantly shallow among the older age groups in subjects with no DR (P < 0.001) and non-STDR (P = 0.027). Average foveal slope in the diabetic subjects was independently and significantly correlated with increase in age (r = −0.241; P < 0.001) and central subfield thickness (r = −0.542; P < 0.001). Conclusion: Changes in foveal slope were seen with increasing age; however, in diabetes these segmental slope changes can be seen in late DR (STDR). PMID:26265635

  16. Optomap ultrawide field imaging identifies additional retinal abnormalities in patients with diabetic retinopathy

    PubMed Central

    Price, Liam D; Au, Stephanie; Chong, N Victor

    2015-01-01

    Purpose To compare diabetic retinopathy (DR) severity grading between Optomap ultrawide field scanning laser ophthalmoscope (UWFSLO) 200° images and an Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard field view. Methods Optomap UWFSLO images (total: 266) were retrospectively selected for evidence of DR from a database of eye clinic attendees. The Optomap UWFSLO images were graded for DR severity by two masked assessors. An ETDRS seven-field mask was overlaid on the Optomap UWFSLO images, and the DR grade was assessed for the region inside the mask. Any interassessor discrepancies were adjudicated by a senior retinal specialist. Kappa agreement levels were used for statistical analysis. Results Fifty images (19%) (P<0.001) were assigned a higher DR level in the Optomap UWFSLO view compared to the ETDRS seven-field view, which resulted in 40 images (15%) (P<0.001) receiving a higher DR severity grade. DR severity grades in the ETDRS seven-field view compared with the Optomap UWFSLO view were identical in 85% (226) of the images and within one severity level in 100% (266) of the images. Agreement between the two views was substantial: unweighted κ was 0.74±0.04 (95% confidence interval: 0.67–0.81) and weighted κ was 0.80±0.03 (95% confidence interval: 0.74–0.86). Conclusion Compared to the ETDRS seven-field view, a significant minority of patients are diagnosed with more severe DR when using the Optomap UWFSLO view. The clinical significance of additional peripheral lesions requires evaluation in future prospective studies using large cohorts. PMID:25848202

  17. Involvement of RhoA/ROCK1 signaling pathway in hyperglycemia-induced microvascular endothelial dysfunction in diabetic retinopathy

    PubMed Central

    Lu, Qian-Yi; Chen, Wei; Lu, Li; Zheng, Zhi; Xu, Xun

    2014-01-01

    Diabetic retinopathy (DR) is a well-known serious complication of diabetes mellitus (DM), and can eventually advance to end-stage blindness. In the early stage of DR, endothelial cell barrier disorganized primarily and tight junction (TJ) protein composition transformed subsequently. The small GTPase RhoA and its downstream effector Rho-associated coiled-coil containing protein kinase 1 (ROCK1) regulate a mass of cellular processes, including cell adherence, proliferation, permeability and apoptosis. Although RhoA inhibitors have provided substantial clinical benefit as hypertonicity therapeutics, their use is limited by complex microenvironment as DR. While ample evidence indicates that TJ can be influenced by the RhoA/ROCK1 signaling, the underlying mechanisms remain incompletely understood. Here, we have uncovered a significant signaling network involved in diabetic retinal microvascular endothelial dysfunction (RMVED). Our results indicated that the activation of RhoA/ROCK1 pathway due to high glucose played a key role in microvascular endothelial cell dysfunction (MVED) by way of directly inducing TJ proteins over-expression during DR. We demonstrated that inhibition of RhoA/ROCK1 may attenuate the hypertonicity of endothelial cell caused by high glucose microenvironment meanwhile. Besides, chemical and pharmacological inhibitors of RhoA/ROCK1 pathway may partly block inflammation due to DR. Simultaneously, the apoptosis aroused by high glucose was also prevented considerably by fasudil, a kind of pharmacological inhibitor of RhoA/ROCK1 pathway. These findings indicate that RhoA/ROCK1 signaling directly modulates MVED, suggesting a novel therapeutic target for DR. PMID:25400825

  18. A Hybrid PSO-DEFS Based Feature Selection for the Identification of Diabetic Retinopathy.

    PubMed

    Balakrishnan, Umarani; Venkatachalapathy, Krishnamurthi; Marimuthu, Girirajkumar S

    2015-01-01

    Diabetic Retinopathy (DR) is an eye disease, which may cause blindness by the upsurge of insulin in blood. The major cause of visual loss in diabetic patient is macular edema. To diagnose and follow up Diabetic Macular Edema (DME), a powerful Optical Coherence Tomography (OCT) technique is used for the clinical assessment. Many existing methods found out the DME affected patients by estimating the fovea thickness. These methods have the issues of lower accuracy and higher time complexity. In order to overwhelm the above limitations, a hybrid approaches based DR detection is introduced in the proposed work. At first, the input image is preprocessed using green channel extraction and median filter. Subsequently, the features are extracted by gradient-based features like Histogram of Oriented Gradient (HOG) with Complete Local Binary Pattern (CLBP). The texture features are concentrated with various rotations to calculate the edges. We present a hybrid feature selection that combines the Particle Swarm Optimization (PSO) and Differential Evolution Feature Selection (DEFS) for minimizing the time complexity. A binary Support Vector Machine (SVM) classifier categorizes the 13 normal and 75 abnormal images from 60 patients. Finally, the patients affected by DR are further classified by Multi-Layer Perceptron (MLP). The experimental results exhibit better performance of accuracy, sensitivity, and specificity than the existing methods.

  19. Addressing risk factors, screening, and preventative treatment for diabetic retinopathy in developing countries: a review.

    PubMed

    Lin, Stephanie; Ramulu, Pradeep; Lamoureux, Ecosse L; Sabanayagam, Charumathi

    2016-05-01

    The number of people with diabetic retinopathy (DR) has increased with the increasing prevalence of diabetes mellitus worldwide, especially in developing countries. In recent years, the successful implementation of public health programs in developed countries has been thought to contribute to decreases in blindness from DR. Developing countries, however, have not seen the same improvements, and their public health interventions still face significant challenges. In this review we describe the current state of public health approaches including risk factor control, screening and treatment techniques for DR in developing countries, and suggest recommendations. While the awareness of DR is variable, specific knowledge about DR is low, such that many patients have already experienced vision loss by the time they are screened. Attempts to improve rates of screening, in particular through non-mydriatic cameras and tele-screening, are ongoing and promising, although challenges include collaboration with healthcare systems and technology failures. Laser treatment is the most readily available, with anti-VEGF therapy and vitreo-retinal surgery increasingly sought after and provided. Recommendations include the use of 'targeted mydriasis' for fundus imaging to address high rates of ungradable images, increased communication with diabetes management services to improve patient retention and mobilization of access to DR treatments.

  20. 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

  1. Continued Reduction in the Prevalence of Retinopathy in Adolescents With Type 1 Diabetes

    PubMed Central

    Downie, Elizabeth; Craig, Maria E.; Hing, Stephen; Cusumano, Janine; Chan, Albert K.F.; Donaghue, Kim C.

    2011-01-01

    OBJECTIVE To examine trends in microvascular complications in adolescents with type 1 diabetes between 1990 and 2009 in Sydney, Australia. RESEARCH DESIGN AND METHODS We used analysis of complications in 1,604 adolescents (54% female, aged 12–20 years, median duration 8.6 years), stratified by four time periods using Generalized Estimation Equations as follows: T1 (1990–1994), T2 (1995–1999), T3 (2000–2004), and T4 (2005–2009). Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) using timed overnight urine collections, and albumin-to-creatinine ratio (ACR) and peripheral nerve function using thermal and vibration threshold. RESULTS Retinopathy declined (53, 38, 23, and 12%; P < 0.001), as did borderline elevation of AER/ACR (45, 30, 26, and 30%; P < 0.001) and microalbuminuria (8, 4, 3, and 3%; P = 0.006). Multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) use increased (17, 54, 75, and 88%; P < 0.001), median HbA1c decreased (9.1, 8.9, 8.5, and 8.5%; P < 0.001), and severe hypoglycemia was unchanged (6, 8, 10, and 7%; P = 0.272). Retinopathy was associated with diabetes duration (odds ratio [OR] 1.12 [95% CI 1.08–1.17]), age (1.13 [1.06–1.20]), HbA1c (1.16 [1.08–1.25]), systolic blood pressure (BP) SDS (1.31 [1.16–1.48]), socioeconomic disadvantage (1.42 [1.04–1.95]), and 1 to 2 injections per day (vs. MDI/CSII; 1.35 [1.05–1.73]); borderline AER/ACR with male sex (1.32 [1.02–1.70]), age (1.19 [1.12–1.26]), HbA1c (1.18 [1.08–1.29]), weight SDS (1.31 [1.21–1.53]), insulin dose per kilograms (1.64 [1.13–2.39]), 1 to 2 injections per day (1.41 [1.08–1.84]), and socioeconomic disadvantage (1.68 [1.23–2.31]); and microalbuminuria with age (1.14 [1.01–1.29]), HbA1c (1.20 [1.05–1.37]), diastolic BP SDS (1.76 [1.26–2.46]), and 1 to 2 injections per day (1.95 [1.11–3.41]). CONCLUSIONS The decline in retinopathy supports contemporary guidelines that

  2. 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

  3. A Case of Proliferative Diabetic Retinopathy with HIV Infection in Which HAART Possibly Influenced the Prognosis of Visual Function

    PubMed Central

    Kitagaki, Takakuni; Sato, Takaki; Hirai, Junko; Kimura, Daisaku; Kakurai, Keigo; Fukumoto, Masanori; Tajiri, Kensuke; Kobayashi, Takatoshi; Kida, Teruyo; Kojima, Shota; Ikeda, Tsunehiko

    2016-01-01

    Background We report on a patient with proliferative diabetic retinopathy (PDR) and human immunodeficiency virus (HIV) infection who exhibited extremely active PDR followed by a rapid onset of blindness in the right eye. The progression of visual disturbance in the patient's left eye was slowed after starting highly active anti-retroviral therapy (HAART), and vision in that eye was rescued after vitrectomy. Case Report A 72-year-old male developed pneumocystis carinii pneumonia stemming from an HIV infection and began HAART at the Department of Hematology, Osaka Medical College, Takatsuki City, Japan. Prior to HAART, the patient had shown rapidly progressing retinopathy in the right eye accompanied by vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma, ultimately leading to early-onset blindness. After starting HAART, the progression of the retinopathy in the left eye became slower compared to the right eye, with corrected visual acuity improving to 0.6 after vitrectomy, despite being accompanied by vitreous hemorrhage. The patient's overall condition has remained stable following the operation, and the condition of the ocular fundus in the left eye has also settled. Conclusion Significant differences were found in the progression rate of PDR with HIV infection between before and after starting HAART. Our findings suggest that early administration of HAART to HIV patients with diabetic retinopathy is crucial for maintaining visual function. PMID:27990117

  4. 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

  5. The Relationship between Serum Carbonic Anhydrase I-II Autoantibody Levels and Diabetic Retinopathy in Type 1 Diabetes Patients

    PubMed Central

    Türk, Adem; Mollamehmetoğlu, Süleyman; Alver, Ahmet; Menteşe, Ahmet; Nuhoğlu, İrfan; Erem, Cihangir; İmamoğlu, Halil İbrahim

    2017-01-01

    Objectives: To investigate the relationship between serum carbonic anhydrase I-II (CA-I and II) autoantibody levels and diabetic retinopathy (DRP) in cases with type 1 diabetes. Materials and Methods: A total of 37 type-1 diabetic patients, 17 with DRP (group 1) and 20 without (group 2), and 38 healthy control subjects (group 3) were included. CA-I and CA-II autoantibody levels were measured in serum samples obtained from each of the three groups and compared statistically. Additionally, the correlation between CA-I and CA-II autoantibody levels and the presence of diabetic macular edema was examined. Results: Mean measured CA-I autoantibody levels were 0.145±0.072, 0.117±0.047, and 0.138±0.061 ABSU in group 1, group 2, and group 3, respectively (p=0.327). The average CA-II autoantibody levels achieved in the same groups were 0.253±0.174, 0.155±0.137, and 0.131±0.085 ABSU, respectively (p=0.005). No significant difference was obtained between the subgroups of group 1, with macular edema (n=8) and without (n=9), in terms of both CA-I and CA-II autoantibody levels (p=0.501, p=0.178, respectively). Conclusion: A significant correlation was observed between the development of DRP and serum CA-II autoantibody levels in type 1 diabetic cases. However, there was no correlation between the autoantibody levels and the presence of diabetic macular edema in cases with DRP.

  6. The Cost-Effectiveness of Three Screening Alternatives for People with Diabetes with No or Early Diabetic Retinopathy

    PubMed Central

    Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Allaire, Benjamin A; Song, Michael S; Klein, Ronald; Saaddine, Jinan B

    2011-01-01

    Objective To determine whether biennial eye evaluation or telemedicine screening are cost-effective alternatives to current recommendations for the estimated 10 million people aged 30–84 with diabetes but no or minimal diabetic retinopathy. Data Sources United Kingdom Prospective Diabetes Study, National Health and Nutrition Examination Survey, American Academy of Ophthalmology Preferred Practice Patterns, Medicare Payment Schedule. Study Design Cost-effectiveness Monte Carlo simulation. Data Collection/Extraction Methods Literature review, analysis of existing surveys. Principal Findings Biennial eye evaluation was the most cost-effective treatment option when the ability to detect other eye conditions was included in the model. Telemedicine was most cost-effective when other eye conditions were not considered or when telemedicine was assumed to detect refractive error. The current annual eye evaluation recommendation was costly compared with either treatment alternative. Self-referral was most cost-effective up to a willingness to pay (WTP) of U.S.$37,600, with either biennial or annual evaluation most cost-effective at higher WTP levels. Conclusions Annual eye evaluations are costly and add little benefit compared with either plausible alternative. More research on the ability of telemedicine to detect other eye conditions is needed to determine whether it is more cost-effective than biennial eye evaluation. PMID:21492158

  7. 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

  8. Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

    PubMed Central

    Zhou, Ai-Yi; Zhou, Chen-Jing; Yao, Jing; Quan, Yan-Long; Ren, Bai-Chao; Wang, Jian-Ming

    2016-01-01

    AIM To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria. METHODS The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated. RESULTS Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular

  9. 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

  10. 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

  11. Problem-solving therapy for adults with diabetic retinopathy and diabetes-specific distress: a pilot randomized controlled trial

    PubMed Central

    Rees, Gwyneth; O'Hare, Fleur; Saeed, Marian; Sudholz, Bronwyn; Sturrock, Bonnie A; Xie, Jing; Speight, Jane; Lamoureux, Ecosse L

    2017-01-01

    Objective To provide preliminary evidence for the impact of problem-solving therapy for diabetes (PST-D) in adults with diabetic retinopathy (DR) and diabetes distress. Research design and methods In a pilot randomized controlled trial, 40 participants with DR and diabetes distress were allocated to the PST-D or control groups. Diabetes distress (DDS), depressive symptoms (PHQ-9), self-care activities (SDSCA), and HbA1c were assessed at baseline, and 3 and 6-month follow-ups. Results At the 6-month follow-up, the PST-D group showed significant improvements relative to the control group, in ‘regimen-related distress’ (PST-D: −1.3±1.4; control: −0.4±1.1), depressive symptoms (PST-D: −4.3±6.1; control: −0.3±4.6), and HbA1c (PST-D: −1.2%±1.01; control: 0.2%±1.2%) (all p<0.05). In multiple regression analysis, adjusting for baseline values and sociodemographic factors, PST-D was associated with significant improvement in ‘regimen-related distress’, depressive symptoms, and HbA1c at the 6-month follow-up (p<0.05). Conclusions PST-D is a promising intervention for improving psychological outcomes and glycemic control. A fully powered study is required to confirm these findings and examine mechanisms of change in HbA1c. Trial registration number ACTRN12616001010482; results. PMID:28243448

  12. Choosing preclinical study models of diabetic retinopathy: key problems for consideration

    PubMed Central

    Mi, Xue-Song; Yuan, Ti-Fei; Ding, Yong; Zhong, Jing-Xiang; So, Kwok-Fai

    2014-01-01

    Diabetic retinopathy (DR) is the most common complication of diabetes mellitus in the eye. Although the clinical treatment for DR has already developed to a relative high level, there are still many urgent problems that need to be investigated in clinical and basic science. Currently, many in vivo animal models and in vitro culture systems have been applied to solve these problems. Many approaches have also been used to establish different DR models. However, till now, there has not been a single study model that can clearly and exactly mimic the developmental process of the human DR. Choosing the suitable model is important, not only for achieving our research goals smoothly, but also, to better match with different experimental proposals in the study. In this review, key problems for consideration in choosing study models of DR are discussed. These problems relate to clinical relevance, different approaches for establishing models, and choice of different species of animals as well as of the specific in vitro culture systems. Attending to these considerations will deepen the understanding on current study models and optimize the experimental design for the final goal of preventing DR. PMID:25429204

  13. Modulation of microglia in the retina: new insights into diabetic retinopathy.

    PubMed

    Arroba, Ana I; Valverde, Ángela M

    2017-03-27

    During last decades, the diagnosis of diabetes has been associated with several chronic complications such as diabetic retinopathy (DR). Recent studies of DR have revealed an inflammatory component, which precedes the detection of alterations in the visual function. During DR, the inflammatory process presents two opposite roles depending on the polarization of resident immune cells of the retina triggering proinflammatory (M1) or antiinflammatory (M2) actions. In an early stage of DR, the M2 response concurs with the M1 and is able to ameliorate inflammation and delay the progression of the disease. However, during the progression of DR, the M1 response is maintained whereas the M2 declines and, in this scenario, the classical proinflammatory signaling pathways are chronically activated leading to retinal neurodegeneration and the loss of visual function. The M1/M2 responses are closely related to the activation and polarization of microglial cells. This review aims to offer an overview of the recent insights into the role of microglial cells during inflammation in DR. We have focused on the possibility of modulating microglia polarization as a new therapeutic strategy in DR treatments.

  14. Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy

    PubMed Central

    Miao, Xiao

    2017-01-01

    Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease. PMID:28265339

  15. Screening for diabetic retinopathy using new mydriasis-free, full-field flicker ERG recording device

    PubMed Central

    Fukuo, Motonobu; Kondo, Mineo; Hirose, Akira; Fukushima, Harumi; Ikesugi, Kengo; Sugimoto, Masahiko; Kato, Kumiko; Uchigata, Yasuko; Kitano, Shigehiko

    2016-01-01

    Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Therefore, it is important to detect DR accurately during mass screening. The purpose of this study was to determine whether a small, hand-held, mydriasis-free, full-field flicker electroretinographic (ERGs) device called RETeval can be used to screen for DR. To accomplish this, we recorded full-field flicker ERGs with this device from 48 normal eyes and 118 eyes with different severities of DR in patients with diabetes mellitus (DM). This system delivered a constant flash retinal luminance by adjusting the flash luminance that compensated for changes in the pupil size. Our results showed that there were significant correlations between the severity of DR and the implicit times (P < 0.001; r = 0.55) and the amplitudes (P = 0.001; r = −0.29). When the implicit time was used for the index, the area under the receiver operating characteristic curve was 0.84 for the detection of DR, and was 0.89 for the detection of DR requiring ophthalmic treatments. These results suggest that the implicit times of the flicker ERGs recorded by the small, mydryasis-free ERG system can be used as an adjunctive tool to screen for DR. PMID:27824158

  16. 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

  17. 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

  18. Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review

    PubMed Central

    2017-01-01

    Background Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus, and more than 75% of patients who have had diabetes for more than 20 years will have some degree of DR. This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age. The current mainstay of treatment is laser photocoagulation, which causes impairment of vision and discomfort to patients. Thus, finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable. Objective To assess the efficacy and safety of the drugs in the statin and/or fibrate groups for the prevention and treatment of DR. Methods In this systematic review, we will select randomized controlled trials of fibrates or statins used for the treatment or prevention of DR. Our search strategy will include free text terms and controlled vocabulary (eg, MeSH, Emtree) for, “diabetic retinopathy”, “statins”, “fibrates”, “hypolipidemic agents”, and for drugs from both groups. Databases that will be used include Medical Literature Analysis and Retrieval System/PubMed, Embase, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Center on Health Sciences Information, Clinicaltrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration’s tool. We will report structured summaries of the included studies and, if possible, conduct meta-analyses. Results This is a protocol for a systematic review, therefore results are not available. We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion. Conclusions

  19. Caspase-14: A novel caspase in the retina with a potential role in diabetic retinopathy

    PubMed Central

    Ahmad, Saif; Megyerdi, Sylvia; Othman, Amira; Baban, Babak; Palenski, Tammy L.; Shin, Eui Seok; Gurel, Zafer; Hsu, Stephen; Sheibani, Nader

    2012-01-01

    Purpose The purpose of this study was to evaluate caspase-14 expression in the retina under normal and diabetic conditions, and to determine whether caspase-14 contributes to retinal microvascular cell death under high glucose conditions. Methods Quantitative real-time polymerase chain reaction and western blot analysis were used to evaluate caspase-14 expression in retinal cells, including pericytes (PCs), endothelial cells (ECs), astrocytes (ACs), choroidal ECs, and retinal pigment epithelium (RPE) cells. We also determined caspase-14 expression in the retinas of human subjects with or without diabetic retinopathy (DR) and in experimental diabetic mice. Retinal ECs and PCs were infected with adenoviruses expressing human caspase-14 or green fluorescent protein. Caspase-14 expression was also assessed in retinal vascular cells cultured under high glucose conditions. The number of apoptotic cells was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling staining and confirmed by determining the levels of cleaved poly (ADP-ribose) polymerase-1 and caspase-3. Results Our experiments demonstrated that retinal ECs, PCs, ACs, choroidal ECs, and RPE cells expressed caspase-14, and DR was associated with upregulation and/or activation of caspase-14 particularly in retinal vasculature. High glucose induced marked elevation of the caspase-14 level in retinal vascular cells. There was a significant increase in the apoptosis rate and the levels of cleaved poly (ADP-ribose) polymerase-1 and caspase-3 in retinal ECs and PCs overexpressing caspase-14. Conclusions Our findings indicate that caspase-14 might play a significant role in the pathogenesis of DR by accelerating retinal PC and EC death. Further investigations are required to elaborate the underlying mechanisms. PMID:22876114

  20. 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.

  1. Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy.

    PubMed

    Zlotcavitch, Leonid; Flynn, Harry W; Avery, Robert L; Rachitskaya, Aleksandra

    2015-01-01

    We report a patient with progression to a macula-off tractional retinal detachment in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection. A 32-year-old diabetic man noted decreased vision in his left eye 1 week following 25 gauge pars plana vitrectomy, gas tamponade, and intraoperative injection of bevacizumab in his right eye. Left eye visual acuity decreased from 20/80 to 20/200, and macula-off tractional retinal detachment was seen on clinical exam and imaging. Progression of tractional retinal detachment associated with proliferative diabetic retinopathy in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection may occur.

  2. 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

  3. Reversal of the Caspase-Dependent Apoptotic Cytotoxicity Pathway by Taurine from Lycium barbarum (Goji Berry) in Human Retinal Pigment Epithelial Cells: Potential Benefit in Diabetic Retinopathy.

    PubMed

    Song, M K; Roufogalis, B D; Huang, T H W

    2012-01-01

    Diabetic retinopathy is a preventable microvascular diabetic complication and a leading cause of vision loss. Retinal pigment epithelial cell apoptosis is an early event in diabetic retinopathy. Taurine is reportedly beneficial for diabetic retinopathy and is abundant in the fruit of Lycium barbarum (LB). We have investigated the effect of pure taurine and an extract of LB rich in taurine on a model of diabetic retinopathy, the retinal ARPE-19 cell line exposed to high glucose. We demonstrate for the first time that LB extract and the active ligand, taurine, dose dependently enhance cell viability following high glucose treatment in the ARPE-19 retinal epithelial cell line. This cytoprotective effect was associated with the attenuation of high glucose-induced apoptosis, which was shown by characteristic morphological staining and the dose-dependent decrease in the number of apoptotic cells, determined by flow cytometry. Moreover, we have shown that LB extract and taurine dose dependently downregulate caspase-3 protein expression and the enzymatic activity of caspase-3. We conclude that taurine, a major component of LB, and the LB extract, have a cytoprotective effect against glucose exposure in a human retinal epithelial cell line and may provide useful approaches to delaying diabetic retinopathy progression.

  4. Reversal of the Caspase-Dependent Apoptotic Cytotoxicity Pathway by Taurine from Lycium barbarum (Goji Berry) in Human Retinal Pigment Epithelial Cells: Potential Benefit in Diabetic Retinopathy

    PubMed Central

    Song, M. K.; Roufogalis, B. D.; Huang, T. H. W.

    2012-01-01

    Diabetic retinopathy is a preventable microvascular diabetic complication and a leading cause of vision loss. Retinal pigment epithelial cell apoptosis is an early event in diabetic retinopathy. Taurine is reportedly beneficial for diabetic retinopathy and is abundant in the fruit of Lycium barbarum (LB). We have investigated the effect of pure taurine and an extract of LB rich in taurine on a model of diabetic retinopathy, the retinal ARPE-19 cell line exposed to high glucose. We demonstrate for the first time that LB extract and the active ligand, taurine, dose dependently enhance cell viability following high glucose treatment in the ARPE-19 retinal epithelial cell line. This cytoprotective effect was associated with the attenuation of high glucose-induced apoptosis, which was shown by characteristic morphological staining and the dose-dependent decrease in the number of apoptotic cells, determined by flow cytometry. Moreover, we have shown that LB extract and taurine dose dependently downregulate caspase-3 protein expression and the enzymatic activity of caspase-3. We conclude that taurine, a major component of LB, and the LB extract, have a cytoprotective effect against glucose exposure in a human retinal epithelial cell line and may provide useful approaches to delaying diabetic retinopathy progression. PMID:22567031

  5. A socioeconomic and behavioral survey of patients with difficult-to-control type 2 diabetes mellitus reveals an association between diabetic retinopathy and educational attainment

    PubMed Central

    Emoto, Naoya; Okajima, Fumitaka; Sugihara, Hitoshi; Goto, Rei

    2016-01-01

    Background We have recently reported that the attitude of patients toward risk could be a factor in the progression of diabetic complications. In general, risk preference is closely related to socioeconomic status (SES), which includes factors such as age, sex, income, and educational attainment. Objective We aimed to determine the effect of SES and behavioral propensity on the progress of diabetic complications in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a survey of 238 patients with difficult-to-control T2DM treated at a hospital in Japan using a modified behavioral economics questionnaire that included questions related to SES. The patients had been referred by general practitioners or other departments in the hospital because of poor metabolic control or unstable complications. Results Educational attainment was significantly associated with progression of retinopathy in patients <65 years of age. Educational attainment of a high school diploma (12 years of education) or lower was a significant risk factor, but there were no differences among levels of attainment beyond high school (13–16 years or more of education). Behavioral propensities were also weakly associated with complications, but not as much as educational attainment. Personal income level and economic status did not show an association with the retinopathy levels. Conclusion Lower educational attainment is a strong risk factor for diabetic retinopathy, and it is independent of the economic status. The result suggests that cognitive function may play an important role in the progression of diabetic retinopathy in patients with T2DM. PMID:27822016

  6. 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

  7. 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.

  8. 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

  9. Functional and Molecular Characterization of Ex Vivo Cultured Epiretinal Membrane Cells from Human Proliferative Diabetic Retinopathy

    PubMed Central

    Veréb, Zoltán; Lumi, Xhevat; Andjelic, Sofija; Globocnik-Petrovic, Mojca; Urbancic, Mojca; Hawlina, Marko; Facskó, Andrea; Petrovski, Goran

    2013-01-01

    Characterization of the cell surface marker phenotype of ex vivo cultured cells growing out of human fibrovascular epiretinal membranes (fvERMs) from proliferative diabetic retinopathy (PDR) can give insight into their function in immunity, angiogenesis, and retinal detachment. FvERMs from uneventful vitrectomies due to PDR were cultured adherently ex vivo. Surface marker analysis, release of immunity- and angiogenesis-pathway-related factors upon TNFα activation and measurement of the intracellular calcium dynamics upon mechano-stimulation using fluorescent dye Fura-2 were all performed. FvERMs formed proliferating cell monolayers when cultured ex vivo, which were negative for endothelial cell markers (CD31, VEGFR2), partially positive for hematopoietic- (CD34, CD47) and mesenchymal stem cell markers (CD73, CD90/Thy-1, and PDGFRβ), and negative for CD105. CD146/MCAM and CD166/ALCAM, previously unreported in cells from fvERMs, were also expressed. Secretion of 11 angiogenesis-related factors (DPPIV/CD26, EG-VEGF/PK1, ET-1, IGFBP-2 and 3, IL-8/CXCL8, MCP-1/CCL2, MMP-9, PTX3/TSG-14, Serpin E1/PAI-1, Serpin F1/PEDF, TIMP-1, and TSP-1) were detected upon TNFα activation of fvERM cells. Mechano-stimulation of these cells induced intracellular calcium propagation representing functional viability and role of these cells in tractional retinal detachment, thus serving as a model for studying tractional forces present in fvERMs in PDR ex vivo. PMID:24195074

  10. Functional and molecular characterization of ex vivo cultured epiretinal membrane cells from human proliferative diabetic retinopathy.

    PubMed

    Veréb, Zoltán; Lumi, Xhevat; Andjelic, Sofija; Globocnik-Petrovic, Mojca; Urbancic, Mojca; Hawlina, Marko; Facskó, Andrea; Petrovski, Goran

    2013-01-01

    Characterization of the cell surface marker phenotype of ex vivo cultured cells growing out of human fibrovascular epiretinal membranes (fvERMs) from proliferative diabetic retinopathy (PDR) can give insight into their function in immunity, angiogenesis, and retinal detachment. FvERMs from uneventful vitrectomies due to PDR were cultured adherently ex vivo. Surface marker analysis, release of immunity- and angiogenesis-pathway-related factors upon TNF α activation and measurement of the intracellular calcium dynamics upon mechano-stimulation using fluorescent dye Fura-2 were all performed. FvERMs formed proliferating cell monolayers when cultured ex vivo, which were negative for endothelial cell markers (CD31, VEGFR2), partially positive for hematopoietic- (CD34, CD47) and mesenchymal stem cell markers (CD73, CD90/Thy-1, and PDGFR β ), and negative for CD105. CD146/MCAM and CD166/ALCAM, previously unreported in cells from fvERMs, were also expressed. Secretion of 11 angiogenesis-related factors (DPPIV/CD26, EG-VEGF/PK1, ET-1, IGFBP-2 and 3, IL-8/CXCL8, MCP-1/CCL2, MMP-9, PTX3/TSG-14, Serpin E1/PAI-1, Serpin F1/PEDF, TIMP-1, and TSP-1) were detected upon TNF α activation of fvERM cells. Mechano-stimulation of these cells induced intracellular calcium propagation representing functional viability and role of these cells in tractional retinal detachment, thus serving as a model for studying tractional forces present in fvERMs in PDR ex vivo.

  11. Anti-angiogenic drugs as an adjunctive therapy in the surgical treatment of diabetic retinopathy.

    PubMed

    Figueroa, Marta S; Contreras, Inés; Noval, Susana

    2009-02-01

    Anti-VEGF drugs may be employed in the surgical treatment of diabetic retinopathy: 1. Prior to surgery. The intravitreal injection of anti-VEGF drugs leads to a significant reduction of neovascularization, with a reduction in the adherence of the fibrovascular complex to the retina. This simplifies viscodelamination and reduces intraoperative bleeding during delamination and segmentation. To minimize the risk of tractional retinal detachment due to the contraction of fibrovascular tissue, vitrectomy must be performed within one week after the injection. 2. To decrease the risk of postoperative bleeding. Recurrent vitreous hemorrhages after vitrectomy are often due to small bleeding from persistent neovascularization. The injection of anti-VEGF drugs at the end of vitrectomy could prevent bleeding from these vessels by blocking the pro-inflammatory stimulus of the surgical procedure. 3. To treat postoperative vitreous hemorrhage. The intravitreal injection of anti-VEGF drugs in patients with postoperative bleeding leads to resolution of the hemorrhage. 4. To treat rubeosis iridis. In eyes with complete panretinal photocoagulation, the combination of cryotherapy and intravitreal anti-VEGF injection in the same surgical procedure produces a disappearance of iris neovascularization together with a long term effect with no recurrences. In neovascular glaucoma, anti-VEGF drugs can also facilitate filtrating surgery.

  12. Simplified Correction of Ischemic Index in Diabetic Retinopathy Evaluated by Ultra-widefield Fluorescein Angiography

    PubMed Central

    Kim, Jeong Hee; Jung, Hyeong-Gi; Chung, Hye Jin; Lee, Kyungmin

    2015-01-01

    Purpose To develop a novel, simplified method for correcting the ischemic index of nonperfused areas in diabetic retinopathy (DR). Methods We performed a retrospective review of 103 eyes with naive DR that underwent ultra-widefield angiography (UWFA) over a year. UWFAs were graded according to the quantity of retinal non-perfusion, and uncorrected ischemic index (UII) and corrected ischemic index (CII) were calculated using a simplified, novel method. Results The average differences between UII and CII in the non-proliferative DR group and the proliferative DR group were 0.7 ± 0.9% in the <25% CII group, 3.0 ± 0.9% in the 25% to 49.9% CII group, and 3.6 ± 0.6% in the >50% CII group, respectively. A CII >25% was critical for determining DR progression (p < 0.001). Conclusions Distortion created by UWFA needs to be corrected because the difference between UII and CII in DR increases with the ischemic index. PMID:26028944

  13. 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.

  14. A Microalbuminuria Threshold to Predict the Risk for the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients

    PubMed Central

    Huang, Yan; Guo, Kaifeng; Lu, Junxi; Zhang, Lei; Yu, Haoyong; Bao, Yuqian; Jia, Weiping

    2012-01-01

    Objective To test the hypothesis that a microalbuminuria (MA) threshold can help predict the risk for the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM)_ patients. Design We conducted a cross-sectional study of 4739 subjects with T2DM and a prospective study of 297 subjects with T2DM in China respectively. Methods Clinical and laboratory data were collected and biologic risk factors associated with any DR were analysed. Results In the cross-sectional study, we found that MA was an independent risk factor for DR development; further, when the patients were divided into MA deciles, odds ratio (ORs) of DR for the patients in the sixth MA decile (10.7 mg/24 h) was 1.579-fold (1.161–2.147) compared to that for patients in the first MA decile. Furthermore, the OR of DR increased with a gradual increase in MA levels. Similarly, in the prospective study, during a mean follow-up of 4.5 years, we found that 51 patients (29.0%) of the 176 subjects with high MA level (10.7–30 mg/24 h) developed DR, while 17 patients (14.1%) of the 121 subjects with lower MA (<10.7 mg/24 h) developed DR, and the relative risk ratio of the development of DR is 2.13(95% CI, 1.58–3.62, P<0.001). Conclusion These data suggest that an MA threshold can predict the risk for the development of DR in type 2 diabetes mellitus, although it is still within the traditionally established normal range. PMID:22590593

  15. 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

  16. Disparities between Ophthalmologists and Patients in Estimating Quality of Life Associated with Diabetic Retinopathy

    PubMed Central

    Zou, Haidong; Xu, Xun; Zhang, Xi

    2015-01-01

    Background This study aimed to evaluate and compare the utility values associated with diabetic retinopathy (DR) in a sample of Chinese patients and ophthalmologists. Methods Utility values were evaluated by both the time trade-off (TTO) and rating scale (RS) methods for 109 eligible patients with DR and 2 experienced ophthalmologists. Patients were stratified by Snellen best-corrected visual acuity (BCVA) in the better-seeing eye. The correlations between the utility values and general vision-related health status measures were analyzed. These utility values were compared with data from two other studies. Results The mean utility values elicited from the patients themselves with the TTO (0.81; SD 0.10) and RS (0.81; SD 0.11) methods were both statistically lower than the mean utility values assessed by ophthalmologists. Significant predictors of patients’ TTO and RS utility values were both LogMAR BCVA in the affected eye and average weighted LogMAR BCVA. DR grade and duration of visual dysfunction were also variables that significantly predicted patients’ TTO utility values. For ophthalmologists, patients’ LogMAR BCVA in the affected eye and in the better eye were the variables that significantly predicted both the TTO and RS utility values. Patients’ education level was also a variable that significantly predicted RS utility values. Moreover, both diabetic macular edema and employment status were significant predictors of TTO and RS utility values, whether from patients or ophthalmologists. There was no difference in mean TTO utility values compared to our American and Canadian patients. Conclusions DR caused a substantial decrease in Chinese patients’ utility values, and ophthalmologists substantially underestimated its effect on patient quality of life. PMID:26630653

  17. Effect of ozone on vascular endothelial growth factor (VEGF) and related inflammatory cytokines in rats with diabetic retinopathy.

    PubMed

    Xie, T Y; Yan, W; Lou, J; Chen, X Y

    2016-05-13

    The aim of this study was to investigate the effect of ozone on inflammatory cytokines in diabetic retinopathy (DR) rats. Male rats (40) weighing 300-360 g were included in this study. Thirty rats were randomly divided into the model and ozone groups after DR was induced by streptozotocin. Ten rats served as the blank group. After the diabetic models were established for one month, the rats in the ozone group were treated with 50 mg/kg ozone coloclysis for one month (three times a week). After the rats were anesthetized by intraperitoneal injection, blood samples from the abdominal aorta were collected, and the supernatant was obtained by centrifugation. Vascular endothelial growth factor (VEGF) and inflammatory cytokine content in the serum was detected by enzyme linked immunosorbent assay. The values of VEGF, intercellular cell adhesion molecule-1, interleukin-1 beta, tumor necrosis factor-a, and IL-6 were significantly different among the three groups (P < 0.05). The cytokine levels in the model group were higher than those in the blank group (P < 0.05). The level of each cytokine in the ozone group was higher than that in the blank group. Compared with the model group, the cytokine levels in the ozone group were significantly reduced (P < 0.05). Ozone had no effect on the blood glucose of diabetic rats. Treatment with ozone coloclysis may effectively reduce the secretion of VEGF and inflammatory cytokines in diabetic retinopathy rats.

  18. 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.

  19. High prevalence in Malawi of sight-threatening retinopathy and visual impairment caused by diabetes: identification of population-specific targets for intervention

    PubMed Central

    Burgess, P I; Allain, T J; García-Fiñana, M; Beare, N A V; Msukwa, G; Harding, S P

    2014-01-01

    Aims To report the prevalence of all grades of diabetic retinopathy and associations with demographic, clinical and biochemical variables in people with diabetes in Southern Malawi. Methods We report baseline data from a 24-month prospective cohort study. Subjects were systematically sampled from two hospital-based, primary care diabetes clinics. Visual acuity, glycaemic control, systolic blood pressure, HIV status, urine albumin–creatinine ratio, and haemoglobin and serum lipid levels were assessed. Retinopathy was graded at an accredited reading centre using modified Wisconsin grading of four-field mydriatic photographs. Results A total of 357 subjects were studied. Of these, 13.4% subjects were HIV-positive and 15.1% had anaemia. The overall prevalence rates of any retinopathy, sight-threatening diabetic retinopathy and proliferative retinopathy were 50.1% (95% CI 44.9–55.3), 29.4% (95% CI 24.7–34.1) and 7.3% (95% CI 4.6–10.0), respectively. In multivariate logistic analysis the presence of sight-threatening retinopathy was associated with duration of diabetes (odds ratio 1.11, 95% CI 1.05–1.17), HbA1c (odds ratio 1.31, 95% CI 1.13–1.50), systolic blood pressure (odds ratio 1.03, 95% CI 1.01–1.04), haemoglobin (odds ratio 0.98, 95% CI 0.96–0.99) and LDL cholesterol (odds ratio 1.63, 95% CI 1.18–2.25). No significant association with HIV status was observed. In all, 3.6 and 1.4% of people in our study cohort had visual acuity worse than 6/18 and 6/60 in the better eye, respectively. Conclusions The present study found a prevalence of sight-threatening retinopathy in diabetes clinics in one Sub-Saharan African country of approximately four times that reported in recent European studies and a prevalence of proliferative retinopathy approximately 10 times higher. The association of sight-threatening retinopathy with lower haemoglobin level is a new finding. Our results highlight the urgent need for provision of services for retinopathy detection

  20. Lycium barbarum (Goji Berry) extracts and its taurine component inhibit PPAR-γ-dependent gene transcription in human retinal pigment epithelial cells: Possible implications for diabetic retinopathy treatment.

    PubMed

    Song, M K; Salam, N K; Roufogalis, Basil D; Huang, T H W

    2011-11-01

    The peroxisome proliferator activated receptor-γ (PPAR-γ) is involved in the pathogenesis of diabetic retinopathy. Diabetic retinopathy is a preventable microvascular diabetic complication that damages human retinal pigment epithelial cells. Taurine is abundant in the fruit of Lycium barbarum (Goji Berry), and is reportedly beneficial for diabetic retinopathy. However, the mechanism of its action is unknown. Hence, we have investigated the mechanism of action of an extract from L. barbarum on a model of diabetic retinopathy, the retinal ARPE-19 cell line, and identified the receptor function of taurine, an active component of L. barbarum (Goji Berry) extract, which is potentially responsible for the protective effect on diabetic retinopathy. We demonstrate for the first time that L. barbarum extract and its taurine component dose-dependently enhance PPAR-γ luciferase activity in HEK293 cell line transfected with PPAR-γ reporter gene. This activity was significantly decreased by a selective PPAR-γ antagonist GW9662. Moreover, L. barbarum extract and taurine dose-dependently enhanced the expression of PPAR-γ mRNA and protein. In an inflammation model where ARPE-19 cells were exposed to high glucose L. barbarum extract and taurine down-regulated the mRNA of pro-inflammatory mediators encoding MMP-9, fibronectin and the protein expression of COX-2 and iNOS proteins. The predicted binding mode of taurine in the PPAR-γ ligand binding site mimics key electrostatic interactions seen with known PPAR-γ agonists. We conclude that PPAR-γ activation by L. barbarum extract is associated with its taurine content and may explain at least in part its use in diabetic retinopathy progression.

  1. 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

  2. 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

  3. Proteasome Activators, PA28α and PA28β, Govern Development of Microvascular Injury in Diabetic Nephropathy and Retinopathy

    PubMed Central

    Mahmoudpour, Ali

    2016-01-01

    Diabetic nephropathy (DN) and diabetic retinopathy (DR) are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice. The improved wellbeing and reduced renal damage was associated with diminished expression of Osteopontin (OPN) and Monocyte Chemoattractant Protein-1 (MCP-1) in the glomeruli of STZ-injected PA28α/PA28β double knockout (Pa28αβDKO) mice and also in cultured mesangial cells and retinal pericytes isolated from Pa28αβDKO mice that were grown in high glucose. The mesangial PA28-mediated expression of OPN under high glucose conditions was suppressed by peptides capable of inhibiting the binding of PA28 to the 20S proteasome. Collectively, our findings demonstrate that diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity in vulnerable perivascular cells resulting in microvascular injury and development of DN and DR. PMID:27830089

  4. 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

  5. Health state utilities in patients with diabetic retinopathy, diabetic macular oedema and age-related macular degeneration: a systematic review

    PubMed Central

    2013-01-01

    Background Health state utility values (HSUVs) are important in the assessment of the cost effectiveness of new interventions. In the case of visual conditions, models generally tend have tended to be built around a set of health states defined by visual acuity (VA). The aim of this review was to assess the impact of VA on HSUVs in patients with diabetic retinopathy, diabetic macular oedema or age-related macular degeneration. Methods A systematic literature search was undertaken in major bibliographic databases to identify articles reporting on the relationship between HSUVs and vision. Data were extracted for population characteristics, visual levels and estimated utilities. Evidence from reported statistical models, where available, was considered in the evaluation of vision in the better-seeing eye and the worse-seeing eye. Due to the heterogeneity of included studies, a narrative synthesis was undertaken. Results Of the 17 relevant studies, 9 studies had data that could be used in the analysis of the impact of vision on HSUVs. Visual loss was associated with a marked impact on health utilities. However, the relationship was not comparable between conditions or by measure of HSUVs. Key results included the finding that overall, self-rated time-trade off estimates were more likely to discriminate between different VA levels than EQ-5D values. Additionally, a stronger correlation was observed between HSUVs and better-seeing eye VA compared to worse-seeing eye VA. Conclusions Visual acuity has a significant impact on HSUVs. Nevertheless, care must be taken in the interpretation and use of estimates in cost-effectiveness models due to differences in measures and population diversity. PMID:24304921

  6. 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

  7. 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

  8. Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

    PubMed Central

    Kutzler, Lydia; Brucklacher, Robert M.; Bronson, Sarah K.; Kimball, Scot R.; Freeman, Willard M.

    2011-01-01

    Background As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies. Methodology/Principal Findings A multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated. Conclusions/Significance These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies. PMID:21249158

  9. Safety of calcium dobesilate in chronic venous disease, diabetic retinopathy and haemorrhoids.

    PubMed

    Allain, Hervé; Ramelet, Albert A; Polard, Elisabeth; Bentué-Ferrer, Danièle

    2004-01-01

    The aim of the present review is to consider the adverse effects and the safety profile of calcium dobesilate. Calcium dobesilate (Doxium) is a veno-tonic drug, which is widely prescribed in more than 60 countries from Europe, Latin America, Asia and the Middle East for three main indications: chronic venous disease, diabetic retinopathy and the symptoms of haemorrhoidal attack. Data sources used for this review comprise the international literature (1970-2003), a postmarketing surveillance (PMS) report for calcium dobesilate from OM Pharma (Geneva, Switzerland) covering the period 1974-1998, and periodic safety update reports (PSUR) covering the period 1995-2003 from the French Regulatory authorities pharmacovigilance database and OM Pharma. Data from the PMS report for 1974-1998 indicated that adverse events with calcium dobesilate did not occur very frequently and had the following distribution in terms of frequency: fever (26%), gastrointestinal disorders (12.5%), skin reactions (8.2%), arthralgia (4.3%), and agranulocytosis (4.3%). No deaths were attributed to calcium dobesilate in the PMS report. Using data on product use in the Swiss Compendium we estimated the prevalence of agranulocytosis to be 0.32 cases/million treated patients, i.e. ten times less than the calculated prevalence of agranulocytosis in the general population. Most adverse events are type B, i.e. rare and unrelated to the pharmacological properties of calcium dobesilate. This review concludes that the risk of an adverse effect with calcium dobesilate 500-1500 mg/day is low and constant over time. The recently raised problem of agranulocytosis (a total of 13 known cases drawn from all data sources) appears to be related to methodological bias. Such a review reinforces the need for a strong international pharmacovigilance organisation using similar methods to detect and analyse the adverse effects of drugs.

  10. 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

  11. Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy

    PubMed Central

    Mitra, Rajendra Narayan; Nichols, Chance A.; Guo, Junjing; Makkia, Rasha; Cooper, Mark J.; Naash, Muna I.; Han, Zongchao

    2017-01-01

    We recently reported that the Ins2Akita 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 Ins2Akita 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 Ins2Akita mice even after 3 months of post-injection. These findings suggest that NP-mediated miR200-b delivery has negatively regulated VEGFR-2 expression in vivo. PMID:27297781

  12. 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.

  13. 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

  14. Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

    PubMed Central

    Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.; Smit, Andries J.; Los, Leonoor I.

    2017-01-01

    Purpose Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. Results Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3–7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 μmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). Conclusions Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients. PMID:28264049

  15. Assessment of awareness of diabetic retinopathy among the diabetics attending the peripheral diabetic clinics in melaka, malaysia.

    PubMed

    Addoor, Krishna R; Krishna, R A; Bhandary, Sulatha V; Khanna, Rajesh; Rao, Lavanya G; Lingam, Kamala D; V S, Binu; Shivaji, Santhosh; Nandannaver, Manjunath

    2011-03-01

    In view of the alarming increase in the incidence of diabetes mellitus in Malaysia, we conducted a study to assess the awareness of complications of diabetes among the diabetics attending the peripheral clinics in Melaka. The study period was from January 2007 to December 2007. 351 patients were included in the study. 79.8% were aware of the complications of diabetes mellitus and 87.2% were aware that diabetes can affect the eyes. However, only 50% of the patients underwent an ophthalmological evaluation. Although awareness was good, the motivation to undergo the assessment was poor.

  16. 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

  17. Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy

    PubMed Central

    Li, Guang-Yi; Li, Zi-Bo; Li, Fang; Dong, Li-Ping; Tang, Liang; Xiang, Ju; Li, Jian-Ming; Bao, Mei-Hua

    2017-01-01

    Type 2 diabetic mellitus (T2DM) is a disease with high prevalence and a major cause for death worldwide. Diabetic retinopathy (DR) is one of the major manifestation of diabetes. Aldehyde dehydrogenease 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. It has been found that the polymorphism in ALDH2 rs671 is probably associated with the risk of T2DM and DR. However, a lot of inconsistency and controversy still exists. In order to get a more precise and comprehensive estimation for the association between ALDH2 polymorphism with the risk of T2DM and DR, we conducted the present meta-analysis. A comprehensive literature search was conducted using databases, such as Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database, for all related studies. The included studies met the inclusion criteria, such as being case-control studies about the association of ALDH2 polymorphism and T2DM or DR susceptibility, with sufficient data for the present analysis. Eight studies with 2374 cases and 6694 controls were involved in the present meta-analysis. The results indicated a significant lower risk of T2DM for *1/*1 genotype in homozygous models (*1/*1 vs. *2/*2, OR = 0.31, 95% CI = 0.11–0.89, p = 0.03) and in the dominant model (*1/*1 vs. *2/*2 + *1/*2, OR = 0.61, 95% CI = 0.37–1.00, p = 0.05). Subgroup analysis by ethnicity found a significant lower risk of T2DM in Chinese in all genotype models. No significant relation was found between ALDH2 rs671 and DR. In conclusion, the current meta-analysis indicated that ALDH2 rs671 was significantly related with T2DM. The ALDH2 rs671 might be able to be used as a predictor for the risk of T2DM. However, due to the existence of heterogeneity and publication bias in the involved studies, our results should be interpreted with caution. PMID:28208752

  18. 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

  19. 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.

  20. Long-Term Outcomes of Primary Trabeculectomy in Diabetic Patients without Retinopathy with Primary Angle-Closure Glaucoma

    PubMed Central

    Liu, Jian; Li, Bin; Wang, Jianrong

    2017-01-01

    Purpose. To evaluate primary trabeculectomy with adjunctive mitomycin-C (MMC) in diabetic patients without retinopathy with primary angle-closure glaucoma (PACG). Design. This is a retrospective case series comparison. Participants. This retrospective trial compared outcomes of 88 eyes that underwent trabeculectomy in patients with diabetes mellitus (DM) without retinopathy and in 97 patients without DM. Methods. In this study, the intraocular pressure (IOP), visual acuity, visual field, and postoperative complications were compared between the two groups. Qualified surgical success is defined as an IOP between 6 and 18 mmHg with or without topical antiglaucoma medication. Results. After a follow-up of 5 years, the IOP decreased from a mean basal IOP of 27.8 ± 7.3 mmHg to 15.0 ± 5.6 mmHg in the DM group and from 27.3 ± 6.0 mmHg to 12.4 ± 5.3 mmHg in the control group. The mean number of antiglaucoma medications was 3.4 ± 1.3 and 3.3 ± 1.2 preoperatively (P = 0.587) whereas it was 1.7 ± 1.5 and 1.1 ± 1.4 at the 5-year follow-up (P = 0.049). The 5-year qualified surgical success rates were 42.9% and 65.4% for both groups (P = 0.046; log-rank test). Encysted blebs were seen in 21 (23.9%) patients in the DM group and in 12 (12.4%) patients in the control group (P = 0.041). Conclusion. PACG patients with DM without retinopathy undergoing primary trabeculectomy with MMC may have a lower long-term surgical survival rate compared with patients without DM. PMID:28337343

  1. 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

  2. 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

  3. 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

  4. Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy.

    PubMed Central

    Limb, G A; Chignell, A H; Green, W; LeRoy, F; Dumonde, D C

    1996-01-01

    AIMS: This study investigated the presence of the cytokine tumour necrosis factor alpha (TNF alpha) and the vascular adhesion glycoproteins ICAM-1, VCAM-1, E-selectin, P-selectin, and PECAM within fibrovascular membranes of eyes with proliferative diabetic retinopathy (PDR). METHODS: The presence of these molecules was determined by immunohistochemical staining using monoclonal antibodies and the APAAP technique. RESULTS: Staining for TNF alpha was observed on the retinal vascular endothelium of five of 12 specimens, on infiltrating cells within all membranes, and on the extracellular matrix of nine specimens. This staining wa abolished by absorption of the monoclonal antibody with human recombinant TNF alpha. Likewise, ICAM-1 staining was given by infiltrating cells and extracellular matrix of nine membranes and by the endothelium of three of the specimens. VCAM-1, E-selectin, and P-selectin staining was observed on the vascular endothelium of 5/12, 4/12, and 3/12 epiretinal membranes respectively. PECAM was expressed by the endothelium of 4/12 specimens, by infiltrating cells of 8/12 membranes, and also by the extracellular matrix of two of the specimens. CONCLUSION: The widespread distribution of TNF alpha and the nature of the adhesion molecules expressed by vascular endothelial cells in PDR membranes suggest that local activation of TNF alpha and enhanced expression of vascular cell adhesion molecules may play an important role in the development of the proliferative phase of diabetic retinopathy. Images PMID:8814750

  5. Attenuation of diabetic retinopathy by enhanced inhibition of MMP-2 and MMP-9 using aspirin and minocycline in streptozotocin-diabetic rats.

    PubMed

    Bhatt, Lokesh Kumar; Addepalli, Veeranjaneyulu

    2010-02-12

    Interruptions of Matrix Metalloproteinase-2 (MMP-2) and Matrix Metalloproteinase-9 (MMP-9) have been shown to reduce the ensuing threatening risk factors of vascular complications of diabetes by alteration in Extracellular Matrix (ECM). We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin, a non-selective COX and tPA inhibitor and this combination can reduce progression of diabetic retinopathy. Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Four weeks after diabetes induction rats were treated with minocycline (50 mg/kg, p.o.) per se, aspirin (50 mg/kg, p.o.) per se, or minocycline in combination with aspirin for a period of four weeks. At the end of eighth week rats were anesthetized and electroretinograms were recorded. B-wave latency, B-wave amplitude and retinal permeability were measured. Histology was done and retinal thickness was measured. Zymography was carried out for MMP-2 and MMP-9 level determinations. B-wave amplitude was significantly decreased while B- wave latency was significantly increased in diabetic group when compared with normo-glycemic rats. Treatment with combination of minocycline and aspirin significantly reversed B-wave amplitude and latency compared with vehicle-treated diabetic controls. Blood retinal permeability and retinal thickness were also significantly attenuated by the treatment of minocycline in combination with aspirin. Results of the present study suggest that MMP-2 and MMP-9 inhibition in presence of COX inhibitor prevents the development of experimental diabetic retinopathy in rats and can be a potential approach for the treatment.

  6. Protective effects of SIRT1 in patients with proliferative diabetic retinopathy via the inhibition of IL-17 expression

    PubMed Central

    LIU, SHULIN; LIN, YU; LIU, XIN

    2016-01-01

    Diabetic retinopathy (DR) is a chronic microvascular complication of diabetes that may lead to loss of vision. The pathogenesis of DR is complex and elevated expression levels of T helper (Th)17 cells and interleukin (IL)-17 have been suggested to be associated with the development and progression of DR. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide+-dependent histone deacetylase that is downregulated in patients with DR. Previous studies have demonstrated that SIRT1 is capable of inhibiting the production of IL-17. In the present study, 19 patients with proliferative diabetic retinopathy (PDR) and 20 non-diabetic controls with idiopathic macular epiretinal membranes were recruited and the SIRT1 expression levels of excised specimens were analyzed using immunohistochemistry. IL-17 expression levels in the sera from patients with PDR and controls were determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, SIRT1 mRNA and protein expression levels in peripheral blood mononuclear cells (PBMCs) from the two groups were analyzed following culture with or without a SIRT1 activator, resveratrol. IL-17 expression levels in the supernatants of PBMCs were determined using ELISA and the results demonstrated that IL-17 expression levels were increased in the sera of patients with PDR, as compared with the controls. Furthermore, increased expression levels of SIRT1 and IL-17 were detected in fibrovascular membranes and PBMCs harvested from patients with PDR, respectively. Notably, SIRT1 mRNA and protein expression levels were decreased in the PBMCs of patients with PDR and IL-17 production was inhibited following SIRT1 activation. The results of the present study indicated that imbalanced IL-17 and SIRT1 expression levels may contribute to the pathogenesis of DR, and SIRT1 may have a protective role in PDR by inhibiting the production of IL-17. PMID:26889251

  7. Effects of photocoagulation on ocular blood flow in patients with severe non-proliferative diabetic retinopathy

    PubMed Central

    Kobayashi, Misato; Yamamoto, Kentaro; Ra, Eimei; Terasaki, Hiroko

    2017-01-01

    Purpose To investigate ocular blood flow and correlations between ocular blood flow and variables in patients with severe non-proliferative diabetic retinopathy (S-NPDR) following panretinal photocoagulation (PRP). Methods In this retrospective, cross-sectional study, the blood flow on the optic nerve head (ONH) and choroid was assessed with laser speckle flowgraphy (LSFG) using the mean blur rate (MBR) in 76 eyes of 76 patients with S-NPDR who underwent PRP, 39 eyes of 39 patients with S-NPDR who did not undergo PRP, and 71 eyes of 71 normal subjects. The correlation between MBR and variables, including visual acuity (VA) and choroidal area determined by binarization method, was analyzed. Results The mean age was 62.9 ± 11.9 years in the S-NPDR with PRP eyes, 55.6 ± 11.4 years in the S-NPDR without PRP eyes, and 60.3 ± 11.1 years in the normal subject eyes. The ONH MBR in vessel and tissue areas and the choroidal MBR were significantly lower in the S-NDR with PRP group than in the other groups (p < 0.001, p < 0.001, and p < 0.001, respectively). The luminal and the stromal areas were significantly smaller in the S-NDR with PRP group than in the other groups (p < 0.001 and p < 0.001, respectively). LogMAR best corrected visual acuity (BCVA) exhibited significant negative correlation with the ONH MBR in vessel (r = −0.386, p < 0.001), tissue (r = −0.348, p < 0.001), and the choroid MBR (r = −0.339, p = 0.002) in the S-NDR with PRP group. Stepwise multiple regression analysis demonstrated that BCVA was a common independent factor associated with the ONH MBR in vessel, tissue, and the choroidal MBR in the S-NDR with PRP group. Conclusions ONH and choroid MBR in addition to choroidal component, including the luminal area, were significantly lower in eyes of patients with S-NPDR after PRP compared with no PRP and normal subjects group. This could suggest that the significantly reduced ocular blood flow in PRP-treated S-NPDR eyes correlated with long

  8. Plasma Plasminogen Activator Inhibitor-1 Is Associated with End-Stage Proliferative Diabetic Retinopathy in the Northern Chinese Han Population

    PubMed Central

    Zhong, Ze-Long; Chen, Song

    2012-01-01

    Objective. To identify predictors of end-stage proliferative diabetic retinopathy (PDR) in a cohort of individuals with type 2 diabetes mellitus (T2DM) from the Northern Chinese Han population. Methods. We investigated characteristics of 153 consecutive diabetic patients with end-stage PDR (62 males, 91 females), 123 consecutive PDR patients without end-stage PDR (48 males, 75 females), and 151 normal subjects (63 males, 88 females). Only one eye of each patient or healthy subject was included in this study. Univariate logistic regression models and multivariate logistic regression models were constructed to evaluate the predictors of end-stage PDR. Results. In univariate analysis, systolic blood pressure, diastolic blood pressure, duration of diabetes, family history of T2DM, and plasminogen activator inhibitor-1 (PAI-1) were significently associated with end-stage PDR. After multivariate analysis, family history of T2DM, plasma PAI-1 levels, smoking, and duration of diabetes were four positive predictors associated with end-stage PDR. Conclusions. Higher plasma levels of PAI-1 were associated with end-stage PDR in the Northern Chinese Han population with T2DM. PMID:23304115

  9. 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

  10. Irisin modulates the association of interleukin-17A with the presence of non-proliferative diabetic retinopathy in patients with type 2 diabetes.

    PubMed

    Wang, Chuan; Wang, Lingshu; Liu, Jinbo; Song, Jun; Sun, Yu; Lin, Peng; Liang, Kai; Liu, Fuqiang; He, Tianyi; Sun, Zheng; Hou, Xinguo; Chen, Li

    2016-08-01

    The role of inflammation in pathogenesis of diabetic retinopathy (DR) is getting increasingly recognized. However, it is unclear whether and how non-proliferative diabetic retinopathy (NPDR) is affected by Interleukin-17A (IL-17A) and Interleukin-22 (IL-22), two well-known inflammatory factors, and irisin, a novel potential anti-inflammatory factor. Here we recruited 40 type 2 diabetes mellitus (T2DM) patients with NPDR, 60 T2DM patients without DR (no-DR), and 20 normal glucose tolerance (NGT) controls. Serum levels of IL-17A, IL-22, and irisin were examined. Compared with NGT and no-DR subjects, NPDR group had significantly higher IL-17A levels. Irisin levels were significantly lower in T2DM patients, while IL-22 levels were not significantly different across all three groups. Multiple logistic regression analysis revealed that IL-17A significantly increased the risk of NPDR (OR = 1.22, P < 0.05) before adjusting for irisin. When irisin was included in the model, neither irisin nor IL-17A was associated with NPDR. Further partial correlation analysis showed that irisin was intrinsically correlated with IL-17A even after multiple adjustment (r = -0.252; P = 0.018). These findings suggest that IL-17A is an independent risk factor of NPDR, and irisin could protect against DR through potential anti-IL-17A effects.

  11. Hydroxychloroquine retinopathy.

    PubMed

    Yusuf, I H; Sharma, S; Luqmani, R; Downes, S M

    2017-03-10

    Hydroxychloroquine (HCQ; Plaquenil) is used increasingly in the management of a variety of autoimmune disorders, with well established roles in dermatology and rheumatology and emerging roles in oncology. Hydroxychloroquine has demonstrated a survival benefit in patients with systemic lupus erythematosus; some clinicians advocate its use in all such patients. However, Hydroxychloroquine and chloroquine (CQ) have been associated with irreversible visual loss due to retinal toxicity. Hydroxychloroquine retinal toxicity is far more common than previously considered; an overall prevalence of 7.5% was identified in patients taking HCQ for greater than 5 years, rising to almost 20% after 20 years of treatment. This review aims to provide an update on HCQ/CQ retinopathy. We summarise emerging treatment indications and evidence of efficacy in systemic disease, risk factors for retinopathy, prevalence among HCQ users, diagnostic tests, and management of HCQ retinopathy. We highlight emerging risk factors such as tamoxifen use, and new guidance on safe dosing, reversing the previous recommendation to use ideal body weight, rather than actual body weight. We summarise uncertainties and the recommendations made by existing HCQ screening programmes. Asian patients with HCQ retinopathy may demonstrate an extramacular or pericentral pattern of disease; visual field testing and retinal imaging should include a wider field for screening in this group. HCQ is generally safe and effective for the treatment of systemic disease but because of the risk of HCQ retinal toxicity, modern screening methods and ideal dosing should be implemented. Guidelines regarding optimal dosing and screening regarding HCQ need to be more widely disseminated.Eye advance online publication, 10 March 2017; doi:10.1038/eye.2016.298.

  12. Perception of care and barriers to treatment in individuals with diabetic retinopathy in India: 11-city 9-state study

    PubMed Central

    Shukla, Rajan; Gudlavalleti, Murthy V. S.; Bandyopadhyay, Souvik; Anchala, Raghupathy; Gudlavalleti, Aashrai Sai Venkat; Jotheeswaran, A. T.; Ramachandra, Srikrishna S.; Singh, Vivek; Vashist, Praveen; Allagh, Komal; Ballabh, Hira Pant; Gilbert, Clare E.

    2016-01-01

    Background: Diabetic retinopathy is a leading cause of visual impairment. Low awareness about the disease and inequitable distribution of care are major challenges in India. Objectives: Assess perception of care and challenges faced in availing care among diabetics. Materials and Methods: The cross-sectional, hospital based survey was conducted in eleven cities. In each city, public and private providers of eye-care were identified. Both multispecialty and standalone facilities were included. Specially designed semi-open ended questionnaires were administered to the clients. Results: 376 diabetics were interviewed in the eye clinics, of whom 62.8% (236) were selected from facilities in cities with a population of 7 million or more. The mean duration of known diabetes was 11.1 (±7.7) years. Half the respondents understood the meaning of adequate glycemic control and 45% reported that they had visual loss when they first presented to an eye facility. Facilities in smaller cities and those with higher educational status were found to be statistically significant predictors of self-reported good/adequate control of diabetes. The correct awareness of glycemic control was significantly high among attending privately-funded facilities and higher educational status. Self-monitoring of glycemic status at home was significantly associated with respondents from larger cities, privately-funded facilities, those who were better educated and reported longer duration of diabetes. Duration of diabetes (41%), poor glycemic control (39.4%) and age (20.7%) were identified as the leading causes of DR. The commonest challenges faced were lifestyle/behavior related. Conclusions: The findings have significant implications for the organization of diabetes services in India. PMID:27144135

  13. Efficacy of intravitreal bevacizumab combined with pan retinal photocoagulation versus panretinal photocoagulation alone in treatment of proliferative diabetic retinopathy

    PubMed Central

    Sameen, Murtaza; Khan, Muhammad Saim; Mukhtar, Ahsan; Yaqub, Muhammad Amer; Ishaq, Mazhar

    2017-01-01

    Objective: To compare effectiveness of pan-retinal photocoagulation alone versus panretinal photocoagulation combined with intravitreal bevacizumab on visual acuity and central macular thickness in patients presenting with proliferative diabetic retinopathy. Methods: This Randomized controlled trial was carried out at Armed Forces Institute of ophthalmology, Pakistan from Jan 2016 to Aug 2016. Seventy six eyes of 50 patients having proliferative diabetic retinopathy and diabetic macular edema were included in the study. All the patients were subjected to detailed clinical examination that included Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), slit lamp examination of anterior and posterior segments. Optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) were carried out and patients were divided in two groups (GP and GI). Three monthly sessions of Pan retinal photocoagulation (PRP) using Pattern Scan Laser (PASCAL) alone was performed in group GP while PRP along with three monthly intravitreal bevacizumab (IVB) was performed in group GI. BCVA and CMT was recorded 04 weeks after the third PRP session in both the groups. Results: Seventy six eyes of 50 patients (38 in each group) were treated with three sessions of PRP alone and PRP with IVB in Group GP and GI respectively. Mean age of the patient in group GP was 57.47± 6.08 years while that in group GI was 55.69 ±6.58. The magnitude of induced change in BCVA was 0.09 ± 0.15 in GP while 0.22 + 0.04 in GI groups while mean induced change in CMT after treatment was 77.44 ± 92.30 um and 117.50 ± 93.82 um in group GP and GI. Conclusion: Laser PRP combined with IVB has superior visual and anatomical outcome than PRP alone in patients with combined presentation of PDR and DME. PMID:28367188

  14. IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling

    PubMed Central

    Qiu, Ao-Wang; Bian, Zheng; Mao, Ping-An; Liu, Qing-Huai

    2016-01-01

    Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2Akita (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling. PMID:27980343

  15. A polymorphism of HMGA1 protects against proliferative diabetic retinopathy by impairing HMGA1-induced VEGFA expression

    PubMed Central

    Chiefari, Eusebio; Ventura, Valeria; Capula, Carmelo; Randazzo, Giorgio; Scorcia, Vincenzo; Fedele, Monica; Arcidiacono, Biagio; Nevolo, Maria Teresa; Bilotta, Francesco Luciano; Vitiello, Michela; Palmieri, Camillo; Gulletta, Elio; Fusco, Alfredo; Foti, Daniela; Vero, Raffaella; Brunetti, Antonio

    2016-01-01

    Diabetic retinopathy (DR) is a major complication of diabetes mellitus, and is the leading cause of blindness in working-age people. Usually, DR progresses from the asymptomatic non-proliferative DR that does not significantly alter vision, to proliferative DR (PDR), which can result in aberrant retinal neovessel formation and blindness. The High-Mobility-Group A1 (HMGA1) protein is a transcriptional master regulator of numerous genes, including metabolic and inflammatory genes, which, by modulating the expression of angiogenic factors, may induce retinal neovascularization, a hallmark of PDR. Herein, we examined the relationship between HMGA1 rs139876191 variant and DR. Results revealed that patients with type 2 diabetes, who were carriers of the HMGA1 rs139876191 variant had a significantly lower risk of developing PDR, compared to non-carrier diabetic patients. From a mechanistic point of view, our findings indicated that, by adversely affecting HMGA1 protein expression and function, the HMGA1 rs139876191 variant played a key role in this protective mechanism by downregulating the expression of vascular endothelial growth factor A (VEGFA), a major activator of neovascularization in DR. These data provide new insights into the pathogenesis and progression of DR, and may offer opportunities for discovering novel biomarkers and therapeutic targets for diagnosis, prevention and treatment of PDR. PMID:27991577

  16. Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus.

    PubMed

    Kirkegaard, C; Nørgaard, K; Snorgaard, O; Bek, T; Larsen, M; Lund-Andersen, H

    1990-06-01

    Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 micrograms octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p less than 0.05), and of the serum levels of IGF-I (p less than 0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin-dependent) diabetes.

  17. Recent Advances (in Diabetes Research)

    MedlinePlus

    ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  18. Diabetes

    MedlinePlus

    ... retinopathy gets worse, it may lead to blindness.Laser surgery can often be used to treat or slow down retinopathy, especially if the problem is found early. People who have diabetes should have an eye exam once a year.Warning signs of eye problemsCall your doctor if you ...

  19. Fractalkine Signaling Attenuates Perivascular Clustering of Microglia and Fibrinogen Leakage during Systemic Inflammation in Mouse Models of Diabetic Retinopathy

    PubMed Central

    Mendiola, Andrew S.; Garza, Rolando; Cardona, Sandra M.; Mythen, Shannon A.; Lira, Sergio A.; Akassoglou, Katerina; Cardona, Astrid E.

    2017-01-01

    Fractalkine (FKN) is a chemokine expressed constitutively by healthy neurons and signals to microglia upon interaction with the FKN receptor, CX3CR1. Signaling between FKN and CX3CR1 transduces inhibitory signals that ameliorate microglial activation and proinflammatory cytokine release in neuroinflammatory conditions. The aim of this study is to determine the mechanisms associated with microglial activation and vascular leakage during diabetic retinopathy (DR) and under conditions of low-level endotoxemia, common in diabetic patients. Utilizing the Ins2Akita strain (Akita), a mouse model of type 1 diabetes, our results show that leakage of the blood-protein fibrin(ogen) into the retina occurs as a result of chronic (4 months) but not acute (1.5 months) hyperglycemia. Conversely, inducing endotoxin-mediated systemic inflammation during acute diabetes resulted in fibrinogen deposition in the retina, a phenotype that was exacerbated in mice lacking CX3CR1 signaling. Systemic inflammation in Cx3cr1−/− mice led to robust perivascular clustering of proliferating microglia in areas of fibrinogen extravasation, and induced IL-1β expression in microglia and astrocytes. Lastly, we determined a protective effect of modulating FKN/CX3CR1 signaling in the diabetic retina. We show that intravitreal (iv) administration of recombinant FKN into diabetic FKN-KO mice, reduced fibrinogen deposition and perivascular clustering of microglia in the retina during systemic inflammation. These data suggest that dysregulated microglial activation via loss of FKN/CX3CR1 signaling disrupts the vascular integrity in retina during systemic inflammation. PMID:28119571

  20. A new imaging technique for retinal vessel oximetry: principles and first clinical results in patients with retinal arterial occlusion and diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Hammer, M.; Riemer, T.; Vilser, W.; Gehlert, S.; Schweitzer, D.

    2009-02-01

    The oxygen saturation of blood inside retinal vessels is an essential measure for the estimation of oxygen supply to the tissue as well as its oxygen consumption. In the current approach, the blood oxygenation is measured by a dual-wavelength technique. Using a fundus camera, equipped with a special dual wavelength transmission filter and a color CCD camera, two monochromatic fundus images at 548 nm and 610 nm were recorded simultaneously. The optical densities of retinal vessels for both wavelengths and their ratio, which is known to be proportional to the oxygen saturation, were calculated. From a health control population, mean arterial and venous oxygen saturations were measured of 98+/-10.1% and 65+/-11.7% with reproducibility of 2.52% and 3.25% respectively. In 10 patients with arterial occlusion, a reduction of the arterial oxygen saturation to 78 +/-17% (mean +/- standard deviation, branch arterial occlusion) and 91+/-11% (central arterial occlusion) respectively was found in the occluded vessel. After 5 days on pentoxifilin therapy, the arterial saturation increased to an average of 93+/-12% or 103 +/-6% respectively. In 70 eyes of 42 patients suffering from diabetic retinopathy, an increase of the venous oxygen saturation with the severity of the retinopathy was found (mild nonproliferative retinopathy: 68.4+/-8.2%, moderate non-proliferative retinopathy: 70.5+/-6.8%, severe non-proliferative retinopathy: 72.4+/-7.6%, proliferative retinopathy 75.7+/-8.3%) due to vessel shunting and diabetic changes of the permeability of vessel walls. These first clinical results demonstrate the ability of an accurate measurement of retinal vessel oxygenation with a very simple setup just requiring a special filter in the illumination path of a fundus camera and dedicated software.

  1. 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.

  2. Effect of topical nepafenac in prevention of macular edema after cataract surgery in patients with non-proliferative diabetic retinopathy

    PubMed Central

    Sarfraz, Muhammad Haroon; Haq, Rana Intisar Ul; Mehboob, Mohammad Asim

    2017-01-01

    Objective: To determine the efficacy of topical Nepafenac (0.1%), administered post-operatively in prevention of Macular Edema (ME), after cataract surgery in patients with Non-Proliferative Diabetic Retinopathy (NPDR). Methods: This randomized control trial was conducted at Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi from Sep 2015 to Sep 2016. Sixty eyes of 60 patients with NPDR underwent phacoemulsification with intraocular lens implantation. Group 1 received 0.1% Nepafenac, 8-hourly, in operated eye after cataract surgery for three months, along with routine post-operative medications. Group-2 received only routine post-operative medications. ME was defined as increase in Central Macular Thickness (CMT) of >10% from pre-operative baseline, measured using spectral domain optical coherence tomography. Results: Mean age of study population was 60.97±4.91 years. Out of 60 patients, 34 (56.7%) were males and 24 (43.3%) were females. Mean pre-operative CMT, 3 months post-operative CMT, mean change in CMT and mean frequency change in CMT of Group-1 was 226.5±10.86µm, 228.83±14.56 µm, 2.33±10.45 µm and 1.05% respectively. Mean pre-operative CMT, three months post-operative CMT, mean change in CMT and mean frequency change in CMT in Group-2 was 223.93±11.69µm, 236.17±16.16 µm, 12.23±12.40µm and 5.51% respectively. ME was observed in one patient (3.3%) in Group-1, and seven patients (23.3%) in Group 2. The difference of mean change in CMT and frequency change in CMT between groups was statistically significant (p<0.05). Conclusion: 0.1% topical Nepafenac is effective in prevention of macular edema after cataract surgery in patients with non-proliferative diabetic retinopathy (NPDR).

  3. The Association of a Genetic Variant in SCAF8-CNKSR3 with Diabetic Kidney Disease and Diabetic Retinopathy in a Chinese Population

    PubMed Central

    Jin, Li; Wang, Tao; Jiang, Song; Chen, Miao; Zhang, Rong; Hu, Cheng

    2017-01-01

    Background. Genome-wide association studies found rs955333 located in 6q25.2 was associated with diabetic kidney disease in multiple ethnic populations, including European Americans, African Americans, and Mexican Americans. We aimed to investigate the association between the variant rs955333 in SCAF8-CNKSR3 and DKD susceptibility in Chinese type 2 diabetes patients. Methods. The variant rs955333 was genotyped in 1884 Chinese type 2 diabetes patients. Associations of the variant rs955333 with DKD and DR susceptibility and related quantitative traits were evaluated. Results. The variant rs955333 was not associated with DKD in our samples, while subjects with genotype GG were associated with DR (P = 0.047, OR = 0.5525 [0.308,0.9911]), and it also showed association with microalbuminuria (P = 0.024, beta = −0.1812 [−0.339, −0.024]). Conclusion. Our data suggests the variant rs955333 was not associated with DKD but showed association with diabetic retinopathy in Chinese type 2 diabetes patients.

  4. 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

  5. Prevalence of referable, sight-threatening retinopathy in type 1 diabetes and its relationship to diabetes duration and systemic risk factors.

    PubMed

    Warwick, A N; Brooks, A P; Osmond, C; Krishnan, R

    2017-02-01

    PurposeThe purpose of the study was to provide contemporary estimates for diabetic retinopathy (DR) prevalence in a well-defined UK cohort of patients with type 1 diabetes (T1DM) and investigate potential risk factors for proliferative diabetic retinopathy (PDR) and diabetic maculopathy.Patients and MethodsFour hundred and sixty four T1DM patients in North Hampshire had T1DM duration, demographic and systemic risk factor data evaluated retrospectively alongside their DR status in 2010 using logistic regression analysis.ResultsOverall prevalence of any retinopathy, PDR, and maculopathy was 71.5%, 6.5%, and 10.8%, respectively. PDR and maculopathy prevalence were 0 and 0.7% for <10 years T1DM duration. PDR prevalence was 4%, 8%, and 16% for 10-19.9 years, 20-29.9, years and ≥30 years duration, respectively. Maculopathy prevalence was 15.6%, 18%, and 11% for 10-19.9 years, 20-29.9 years, and ≥30 years duration, respectively. In univariate analysis, PDR was associated with T1DM duration (odds ratio (OR) 1.07/year), age (OR 1.03/year), systolic blood pressure (OR 1.03/mmHg), and antihypertensive therapy (OR 10.63), while maculopathy was associated with duration (OR 1.03/year) and statin therapy (OR 2.83). In multivariate analysis, disease duration (OR 1.07/year) and antihypertensive therapy (OR 6.87) remained significantly associated with PDR, and maculopathy with statin therapy (OR 2.27).ConclusionThis study confirms T1DM duration is a strong risk factor for sight-threatening DR. Maculopathy and PDR prevalence within 10 years of T1DM diagnosis is very low. PDR prevalence at 10-20 years was 4% and then doubled for every 10-year interval thereafter up to 16% with ≥30 years duration. Antihypertensive therapy and statin therapy were strongly associated with PDR and maculopathy, respectively.

  6. 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.

  7. 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.

  8. Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy

    PubMed Central

    Babapoor-Farrokhran, Savalan; Jee, Kathleen; Puchner, Brooks; Hassan, Syed Junaid; Xin, Xiaoban; Rodrigues, Murilo; Kashiwabuchi, Fabiana; Ma, Tao; Hu, Ke; Deshpande, Monika; Daoud, Yassine; Solomon, Sharon; Wenick, Adam; Lutty, Gerard A.; Semenza, Gregg L.; Montaner, Silvia; Sodhi, Akrit

    2015-01-01

    Diabetic eye disease is the most common cause of severe vision loss in the working-age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In PDR, retinal ischemia leads to the up-regulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization in some, but not all, diabetic patients, implicating additional factor(s) in PDR pathogenesis. Here we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identify angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from PDR patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of PDR and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease. PMID:26039997

  9. The tele-screening model for diabetic retinopathy: evaluating the influence of mydriasis on the gradability of a single-field 45 degrees digital fundus image.

    PubMed

    Raman, Rajiv; Rani, Padmaja Kumari; Mahajan, Sheshadri; Paul, Pradeep; Gnanamoorthy, P; Krishna, M S; Sharma, Tarun

    2007-10-01

    The purpose of this article was to study the influence of pupillary dilatation on the gradability of a single-field 45 degrees digital fundus images taken in a telescreening model for diabetic retinopathy. Telescreening camps for diabetic retinopathy were organized in rural south India. Sixty-eight patients with type 2 diabetes were enrolled. Single-field 45 degrees digital fundus images were obtained before (group I) and after pupillary dilatation (group II). Digital fundus images were obtained using nonmydriatic fundus camera and transmitted in real time to the base hospital for grading by a retinal specialist. Various factors that could influence the gradability of images were studied, including patients' age and visual acuity, experience of the photographer, and interobserver variability. After pupillary dilatation, the nongradability of digital fundus images was reduced from 29.1% to 8.6%. With each line of improvement in Snellen's Visual acuity, the gradability improved by 12.1%; likewise, with each year of age, the gradability improved by 5.5% following mydriasis. Interobserver variation was excellent (k = 0.88). The learning curve of photographer had no effect on image gradability. Pupillary dilatation improves the gradability of a single-field 45 degrees digital fundus image during telescreening of diabetic retinopathy.

  10. New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes

    DTIC Science & Technology

    2006-11-01

    32 Genetic Screening in Diabetes : Candidate Gene Analysis for Diabetic Nephropathy University of Hawaii... treatment and prevention of life threatening disease. The overall goal of the research project is to provide a means to genetically test diabetic ...patients for their inherited risk for developing the 3 principal complications of diabetes , i.e., nephropathy , neuropathy, and retinopathy. The

  11. An averaging method for the interpretation of the Farnsworth-Munsell 100-Hue Test--II. Colour vision defects acquired in diabetic retinopathy.

    PubMed

    Birch, J; Dain, S J

    1987-01-01

    The Farnsworth-Munsell 100-Hue test is frequently used to assess acquired colour vision defects. In diabetic retinopathy the acquired defect is a mild or severe type III (Tritan) defect which may be coupled with poor overall hue discrimination. In consequence, error scores are often high and the 100-Hue polar diagram is difficult to interpret. In this study the averaging method of analysis proposed by Dain and Birch is used to examine 120 100-Hue plots obtained by patients with proliferative diabetic retinopathy. These plots have either moderate (150-300) or high error scores (greater than 300). The method of analysis is found to be effective in determining whether a Tritan defect is present or not.

  12. A bibliometric analysis of academic publication on diabetic retinopathy disease trends during 1980-2014: a global and medical view

    PubMed Central

    Caglar, Cagatay; Demir, Emre; Kucukler, Ferit Kerim; Durmus, Mustafa

    2016-01-01

    AIM To investigate diabetic retinopathy (DR) literature using the Institute for Scientific Information (ISI) Web of Science (WoS) database and to analyse the correlation results between socio-economic development datas and number of DR publications. METHODS The statistical analysis of the documents published during 1980-2014 was analysed. The data of this study were based on the database of WoS. “Diabetic retinopathy” was used as the keywords to search the WoS database. RESULTS The United States ranked first in the DR research with 1840 publications and 24.38% of the world production followed by England and Japan. Besides, the most productive country was Iceland. A high correlation was found between number of publications and 2014 gross domestic product (GDP) values of 81 countries (r=0.800, P<0.001). We found a significant correlation between number of publications and Human Development Index (HDI) (r=0.645, P=0.001). There is a moderate correlation between people with diabetes and number of DR publications for 81 countries (r=0.514, P<0.01). It could be analysed that estimated publication number with DR title will be 445 according to the regression curve constituted with cubic model in 2015 (R2=1.000). CONCLUSION More DR studies have been published in developed countries, DR and other complications of diabetes have gradually increased in developing countries over recent decades. It can be expected that the number of DR studies will gradually increase in developing countries. PMID:27990373

  13. Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema

    PubMed Central

    Lammer, Jan; Prager, Sonja G.; Cheney, Michael C.; Ahmed, Amel; Radwan, Salma H.; Burns, Stephen A.; Silva, Paolo S.; Sun, Jennifer K.

    2016-01-01

    Purpose To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Methods Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Results Fifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Conclusions Although absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM. PMID:27926754

  14. 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

  15. Intraocular and systemic levels of vascular endothelial growth factor in advanced cases of retinopathy of prematurity

    PubMed Central

    Velez-Montoya, Raul; Clapp, Carmen; Rivera, Jose Carlos; Garcia-Aguirre, Gerardo; Morales-Cantón, Virgilio; Fromow-Guerra, Jans; Guerrero-Naranjo, Jose Luis; Quiroz-Mercado, Hugo

    2010-01-01

    Purpose: To measure vitreous, aqueous, subretinal fluid and plasma levels of vascular endothelial growth factor in late stages of retinopathy of prematurity. Methods: Interventional study. We enrolled patients with clinical diagnoses of bilateral stage V retinopathy of prematurity, confirmed by b-scan ultrasound and programmed for vitrectomy. During surgery we took samples from blood, aqueous, vitreous, and subretinal fluids. The vascular endothelial growth factor concentration in each sample was measured by ELISA reaction. A control sample of aqueous, vitreous and blood was taken from patients with congenital cataract programmed for phacoemulsification. For statistical analysis, a Mann–Whitney and a Wilcoxon W test was done with a significant P value of 0.05. Results: We took samples of 16 consecutive patients who met the inclusion criteria. The vascular endothelial growth factor levels in the study group were: aqueous, 76.81 ± 61.89 pg/mL; vitreous, 118.53 ± 65.87 pg/mL; subretinal fluid, 1636.58 ± 356.47 pg/mL; and plasma, 74.64 ± 43.94 pg/mL. There was a statistical difference between the study and the control group (P < 0.001) in the aqueous and vitreous samples. Conclusion: Stage 5 retinopathy of prematurity has elevated intraocular levels of vascular endothelial growth factor, which remains high despite severe retinal lesion. There was no statistical difference in plasma levels of the molecule between the control and study group. PMID:20856587

  16. Novel Transgenic Mouse Models Develop Retinal Changes Associated with Early Diabetic Retinopathy Similar to Those Observed in Rats with Diabetes Mellitus

    PubMed Central

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

    2014-01-01

    Retinal capillary pericyte degeneration has been linked to aldose reductase (AR) activity in diabetic retinopathy (DR). Since the development of DR in mice and rats has been reported to differ and that this may be linked to differences in retinal sorbitol levels, we have established new murine models of early onset diabetes mellitus as tools for investigating the role of AR in DR. Transgenic diabetic mouse models were developed by crossbreeding diabetic C57BL/6-Ins2Akita/J (AK) with transgenic C57BL mice expressing green fluorescent protein (GFP), human aldose reductase (hAR) or both in vascular tissues containing smooth muscle actin-α (SMAA). Changes in retinal sorbitol levels were determined by HPLC while changes of growth factors and signaling were investigated by Western Blots. Retinal vascular changes were quantitatively analyzed on elastase-digestion flat mounts. Results show that sorbitol levels were higher in neural retinas of diabetic AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors VEGF, IGF-1, bFGF and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK, and P-44/42 MAPK. Increased loss of nuclei per capillary length and a significant increase in the percentage of acellular capillaries presented in 18 week old AK-SMAA-GFP-hAR mice. These changes are similar to those observed in streptozotocin-induced diabetic rats. Retinal changes in both mice and rats were prevented by inhibition of AR. These studies confirm that the increased expression of AR in mice results in the development of retinal changes associated with the early stages of DR that are similar to those observed in rats. PMID:24370601

  17. 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.

  18. Association of insulin treatment versus oral hypoglycaemic agents with diabetic retinopathy and its severity in type 2 diabetes patients in Cameroon, sub-Saharan Africa

    PubMed Central

    Jingi, Ahmadou M.; Essouma, Mickael; Bigna, Jean Joel R.; Nansseu, Jobert Richie N.; Ellong, Augustin; Mvogo, Côme Ebana

    2016-01-01

    Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with multiple macro and microvascular complications, diabetic retinopathy (DR) being the commonest one. Recent literature has reported an increased risk of DR with insulin use. Methods We carried out a cross-sectional study at the Ophthalmology Department of the Douala General Hospital (DGH) during a 2-year period to explore the association between insulin treatment and both DR and its severity as compared with oral hypoglycemic agents (OHAs) in Cameroonian T2DM patients aged ≥35 years, and who were all screened for DR through eye examination including exhaustive retinal evaluation. Results In total, medical files of 134 T2DM patients were analyzed. The frequency of DR was 54.1% among patients on OHA and 73.9% among those on insulin treatment, giving an overall frequency of 57.5%. There were significantly more OHA treated patients than insulin treated patients (82.8% vs. 17.2%, P<0.001). As expected, both the OHA and insulin groups were comparable by age, sex, duration of diabetes, past history of hypertension, alcohol misuse, and current tobacco smoking. DR was almost significantly more frequent in T2DM patients under insulin regimen than in patients under OHA [73.9% vs. 54.1%; odds ratio (OR) 2.4; 95% confidence interval (CI), 0.9–6.6; P=0.06]. Proliferative diabetic retinopathy (PDR) was significantly more observed in insulin treated patients than in OHA treated patients (34.8% vs. 15.3%; OR 2.95; 95% CI, 1.1–8; P=0.035). Irrespective of staging, the frequency of diabetic macular edema (DME) was significantly higher in the insulin group than in the OHA group (43.5% vs. 19.8%; OR 3.1; 95% CI, 1.2–8; P=0.019). Conclusions Compared with OHA, insulin therapy may be associated with DR, DR severity and DME in these T2DM sub-Saharan African patients. PMID:27867947

  19. Association between eNOS 4b/a Polymorphism and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: A Meta-Analysis

    PubMed Central

    Ma, Ze-jun; Chen, Rui; Ren, Hui-Zhu; Guo, Xin; Guo, Jun; Chen, Li-ming

    2014-01-01

    Many studies have assessed the association between eNOS-4b/a polymorphism and the risk of diabetic retinopathy (DR) among type 2 diabetic subjects. However, the results are inconsistent. In order to derive a more precise estimation of the association, a meta-analysis was conducted. Fifteen studies with 3, 183 cases and 3, 410 controls were enrolled by searching the databases of Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The main analysis indicated no significant association between eNOS-4b/a polymorphism and the risk of DR in overall population [allelic model: OR = 0.94 (0.79–1.11); additive model: OR = 0.91 (0.73–1.14); recessive model: OR = 1.01 (0.81–1.25); dominant model: OR = 0.91 (0.75–1.09)]. Subgroup analysis by ethnicity also indicated no significant association. In conclusion, the current meta-analysis did not observe any association between the polymorphism of eNOS 4b/a and the risk of DR among type 2 diabetic subjects. However, larger well-designed studies are required to confirm this finding. PMID:24895640

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

    PubMed

    Um, Taewoong; Lee, Dong Hoon; Kang, Joon-Won; Kim, Eun Young; Yoon, Young Hee

    2016-08-01

    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.

  1. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    PubMed

    Takeuchi, Masaru; Sato, Tomohito; Tanaka, Atsushi; Muraoka, Tadashi; Taguchi, Manzo; Sakurai, Yutaka; Karasawa, Yoko; Ito, Masataka

    2015-01-01

    Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM), 26 patients with idiopathic macular hole (MH), and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  2. Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway.

    PubMed

    Zhao, Shuzhi; Li, Jun; Wang, Na; Zheng, Bingqing; Li, Tao; Gu, Qing; Xu, Xun; Zheng, Zhi

    2015-10-01

    Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid‑lowering therapeutic agent in clinical use, exerts a potential anti‑inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+‑dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR). The data demonstrated that high glucose treatment in human retinal endothelial cells (HRECs) inhibited the expression and deacetylase activity of SIRT1. The reduction of SIRT1 expression and deacetylase activity persisted following a return to normal glucose levels. Furthermore, nuclear factor‑κB expression was observed to be negatively correlated with SIRT1 expression and activity in HRECs under high glucose levels and the subsequent return to normal glucose levels. Fenofibrate treatment abrogated these changes. Knockdown of SIRT1 attenuated the effect of fenofibrate on high glucose‑induced NF‑κB expression. In addition, fenofibrate upregulated SIRT1 expression through peroxisome proliferator‑activated receptor α in high glucose‑induced metabolic memory. These findings indicate that fenofibrate is important in anti‑inflammatory processes and suppresses the cellular metabolic memory of high glucose‑induced stress via the SIRT1‑dependent signalling pathway. Thus, treatment with fenofibrate may offer a promising therapeutic strategy for halting the development of DR and other complications of diabetes.

  3. 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.

  4. Abnormal sleep patterns in subjects with type II diabetes mellitus and its effect on diabetic microangiopathies: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 20).

    PubMed

    Raman, Rajiv; Gupta, Aditi; Venkatesh, Kadri; Kulothungan, Vaitheeswaran; Sharma, Tarun

    2012-08-01

    To study the prevalence of Abnormal Sleep Patterns (ASPs), gender-wise, in subjects with type II diabetes mellitus and its influence on diabetic microangiopathies. A population-based cross-sectional survey was conducted among 1,414 patients having type II diabetes mellitus. Diabetic retinopathy was graded using stereoscopic digital fundus photography. Neuropathy was assessed by measuring vibration perception threshold using a sensitometer. Nephropathy was diagnosed by the presence of microalbuminuria in the first morning urine sample. ASPs were defined as either short (less than 5 h) or long (more than 9 h) duration of sleep with excessive daytime sleepiness. The Epworth Sleepiness Scale (ESS) score was assessed to note excessive daytime sleepiness; a score of more than 10 was considered as abnormal. The prevalence of ASPs was more in subjects with diabetes than with those without diabetes (14.8 vs. 6.6%) (P = 0.009), especially in women (15.7 vs. 5.6%) (P = 0.021). Likewise, the prevalence of short duration of sleep was higher in subjects with diabetes compared to those without diabetes (6.6 vs. 2.2%) (P = 0.040). The mean age of women subjects with diabetes, having ASPs, was higher than those without diabetes (56.4 ± 8.9 years vs. 47.2 ± 5.9 years, P = 0.033). Women subjects with ASPs had a higher risk of diabetic neuropathy on both univariate and multivariate analysis. ASPs are not only related to diabetes but can also influence the microvascular complications arising due to diabetes, particularly diabetic neuropathy. Diabetology and sleep medicine specialists need to work together to prevent the negative interactions between these two groups.

  5. Red krypton and blue-green argon panretinal laser photocoagulation for proliferative diabetic retinopathy: a laboratory and clinical comparison.

    PubMed Central

    Blankenship, G W

    1986-01-01

    The effects of PRP with red krypton laser are essentially identical to those produced with blue-green argon laser. Burns of the rabbit retina produced with these two different lasers are almost the same. In a prospective and randomized clinical trial of proliferative diabetic retinopathy treatment there was no significant difference between PRP using these two different lasers. The characteristic changes of rabbit fundi 3, 7, and 30 days after PRP with red krypton laser were almost the same as those following blue-green argon laser. Both types of treatment frequently produced small vitreous hemorrhages and exudative retinal detachments, but choroidal thickening occurred more frequently with argon treatment. These changes were transient and had resolved within 30 days of treatment. The microscopic changes consisted of pigment epithelial disruption with pigment migration into the retina, heat coagulation of the photoreceptors, disruption of the outer and inner nuclear layers with atrophy of the nuclei, and temporary swelling of the nerve fiber layer. The untreated retina and choroid between burns was not involved and appeared normal at each period. Thirty days after treatment, the scarring produced by these two types of burns was identical. Seventy-one eyes with proliferative diabetic retinopathy having three or four retinopathy risk factors were treated with panretinal laser photocoagulation, and followed in a prospective study for 6 months. Thirty-six eyes were randomly selected for blue-green argon treatment, and 35 were randomly selected for red krypton treatment. The incidence of undesired side effects during the first 2 weeks following treatment was almost identical between the two groups. However, by 1 month the majority of eyes in both groups had visual acuities equal to or better than the pretreatment acuities and complete regression of NVD. Six months after treatment, the majority of eyes in both groups continued to have visual acuities equal to or better

  6. Depression and Advanced Complications of Diabetes

    PubMed Central

    Lin, Elizabeth H.B.; Rutter, Carolyn M.; Katon, Wayne; Heckbert, Susan R.; Ciechanowski, Paul; Oliver, Malia M.; Ludman, Evette J.; Young, Bessie A.; Williams, Lisa H.; McCulloch, David K.; Von Korff, Michael

    2010-01-01

    OBJECTIVE To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000–2002 and followed through 2005–2007. Advanced microvascular complications included blindness, end-stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures, and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5-year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes. RESULTS After adjustment for prior complications and demographic, clinical, and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes (hazard ratio 1.36 [95% CI 1.05–1.75]) and adverse macrovascular outcomes (1.24 [1.0–1.54]). CONCLUSIONS Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with comorbid depression. PMID:19933989

  7. The Association between VDR Gene Polymorphisms and Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis

    PubMed Central

    Xia, Wei; Lu, Ping

    2016-01-01

    Aims. Studies on the associations of vitamin D receptor (VDR) gene polymorphisms with diabetic retinopathy (DR) susceptibility reported conflicting results. A systematic meta-analysis was undertaken to clarify this topic. Methods. A systematic search of electronic databases (PubMed, EMBASE, and CNKI) was carried out until March 31, 2016. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. Results. A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (649 cases and 707 controls). Pooled ORs showed a significant association between FokI polymorphism and DR risk in all the four genetic models (OR = 1.612 (1.354~1.921), 1.988 (1.481~2.668), 1.889 (1.424~2.505), and 2.674 (1.493~4.790) in allelic, dominant, recessive, and additive models, resp., PZ < 0.01), but not for TaqI or BsmI polymorphism (PZ > 0.05). Similar results were found in the subgroup analysis. Sensitivity analysis indicated that the results were relatively stable and reliable. Results of Begg's and Egger's tests suggested a lack of publication bias. Conclusions. Our meta-analysis demonstrated that DR was significantly associated with VDR gene FokI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be done to confirm the findings. PMID:27891515

  8. Plantar fascia enthesopathy is highly prevalent in diabetic patients without peripheral neuropathy and correlates with retinopathy and impaired kidney function

    PubMed Central

    Arturi, Franco; Nicolosi, Kassandra; Ammendolia, Antonio; D’Angelo, Salvatore; Russo, Emilio; Naty, Saverio; Bruno, Caterina; De Sarro, Giovambattista; Olivieri, Ignazio; Grembiale, Rosa Daniela

    2017-01-01

    Background Aim of this study was to evaluate the prevalence of plantar fascia (PF) enthesopathy in Type 2 diabetes mellitus (T2DM) patients without distal peripheral neuropathy (DPN). Methods We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI). All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF. Results PF thickness was significantly higher in T2DM patients (p<0.0001). T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002), enthesophyte (p = 0.02) and cortical irregularity (p = 0.02). The overall sum of abnormalities was higher in T2DM patients (p<0.0001), as was the percentage of bilateral involvement (p = 0.005). In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05) and enthesophytes (OR 5.13, p = 0.001); reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04); body mass index (BMI) predicted cortical irregularity (OR 0.87, p = 0.05); mean glucose predicted enthesophyte (OR 1.01, p = 0.03); LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02). Conclusions Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN. PMID:28358891

  9. Comparison of Serum Apolipoproteins and Traditional Lipids in Eyes with Diabetic Retinopathy in Indian Population: A Case Series

    PubMed Central

    Prakash, Gunjan; Agrawal, Rachit; Satsangi, S. K.; Prakash, Shikha

    2016-01-01

    Purpose: To review the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy (DR). Materials and Methods: This was a cross-sectional study of patients of DR. DR was graded according to modified Airlie House Classification system. Traditional serum lipids (total, low-density lipoprotein [LDL], and high-density lipoprotein [HDL] cholesterol and triglycerides [TGs]), apolipoprotein AI (apoAI), apolipoprotein B (apoB), and apoB-to-apoAI ratios were assessed. The analysis of variance test was applied. P < 0.05 was considered statistically significant, and P < 0.001 was considered highly significant. Results: Twenty-four patients with DR were evaluated. Serum apoAI was statistically significantly associated with a reduced likelihood of having more severe DR levels (P < 0.001). Increasing levels of apoB (P < 0.001) and apoB-to-apoAI ratio (P < 0.001) were statistically significantly associated with increasing DR severity levels. The association of total (P > 0.05) and LDL cholesterol (P > 0.05) with severity of DR was not statistically significant. HDL cholesterol levels were inversely associated with the severity of DR (P < 0.05). TGs were also statistically significantly associated with the severity of DR (P < 0.05). Conclusion: Serum apolipoprotein levels may be stronger biomarkers of DR than traditional lipids. PMID:27162455

  10. 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.

  11. Intravitreal AAV2.COMP-Ang1 Prevents Neurovascular Degeneration in a Murine Model of Diabetic Retinopathy

    PubMed Central

    Cahoon, Judd M.; Rai, Ruju R.; Carroll, Lara S.; Uehara, Hironori; Zhang, Xiaohui; Medina, Reinhold J.; Das, Subtrata K.; Muddana, Santosh K.; Olson, Paul R.; Nielson, Spencer; Walker, Kortnie; Flood, Maggie M.; Messenger, Wyatt B.; Archer, Bonnie J.; Barabas, Peter; Krizaj, David; Gibson, Christopher C.; Li, Dean Y.; Koh, Gou Y.; Gao, Guangping; Stitt, Alan W.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here, we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable with nondiabetic controls. In late DR, AAV2.COMP-Ang1 enhanced the therapeutic benefit of intravitreally delivered endothelial colony-forming cells by promoting their integration into the vasculature and thereby stemming further visual decline. AAV2.COMP-Ang1 single-dose gene therapy can prevent neurovascular pathology, support vascular regeneration, and stabilize vision in DR. PMID:26340930

  12. Genetic algorithm based feature selection combined with dual classification for the automated detection of proliferative diabetic retinopathy.

    PubMed

    Welikala, R A; Fraz, M M; Dehmeshki, J; Hoppe, A; Tah, V; Mann, S; Williamson, T H; Barman, S A

    2015-07-01

    Proliferative diabetic retinopathy (PDR) is a condition that carries a high risk of severe visual impairment. The hallmark of PDR is the growth of abnormal new vessels. In this paper, an automated method for the detection of new vessels from retinal images is presented. This method is based on a dual classification approach. Two vessel segmentation approaches are applied to create two separate binary vessel map which each hold vital information. Local morphology features are measured from each binary vessel map to produce two separate 4-D feature vectors. Independent classification is performed for each feature vector using a support vector machine (SVM) classifier. The system then combines these individual outcomes to produce a final decision. This is followed by the creation of additional features to generate 21-D feature vectors, which feed into a genetic algorithm based feature selection approach with the objective of finding feature subsets that improve the performance of the classification. Sensitivity and specificity results using a dataset of 60 images are 0.9138 and 0.9600, respectively, on a per patch basis and 1.000 and 0.975, respectively, on a per image basis.

  13. Detection of low-abundance biomarker lipocalin 1 for diabetic retinopathy using optoelectrokinetic bead-based immunosensing.

    PubMed

    Wang, Jhih-Cheng; Ku, Hu-Yao; Chen, Tain-Song; Chuang, Han-Sheng

    2017-03-15

    Early diagnosis of diabetic retinopathy (DR) is vital but challenging. DR is a common complication and a major cause of vision loss in patients with diabetes mellitus. Without appropriate medical intervention, visual impairment may become a great burden to our healthcare system. In clinical practice, the current diagnostic methods, such as fluorescence angiography and optical coherence tomography, remain constrained by non-quantitative examinations and individual ophthalmologists' experiences. Late diagnosis often prevents early treatment. To address the constraints on current diagnostics, this study developed an optoelectrokinetic bead-based immunosensing technique for detecting lipocalin 1 (LCN1), a DR biomarker. The concentration level of LCN1 in the tears of DR patients increases with DR severity. The immunoassay was dependent on the formation of sandwiched immunocomplexes on the particles. A secondary antibody labeled with dyes/quantum dots (QDs) was used to visualize the presence of the target antigens. Rapid electrokinetic patterning (REP), an optoelectrokinetic technique, was used to dynamically enhance the fluorescent signal by concentrating the modified particles. The limit of detection (LOD) of the technique could reach 110pg/mL. Only 1.5μL of a sample fluid was required for the measurement. Our results showed that highly sensitive and improved LOD is subjected to particle stacking, small particle size, and compact cluster. By labeling different particle sizes with dyes/QDs for LCN1 and TNF-α, we successfully used REP to detect the two DR biomarkers on the same platform. The development of an optoelectrokinetic bead-based immunosensing technique can provide new insights into diagnosing other low-abundance diseases in the future.

  14. 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.

  15. Eye care infrastructure and human resources for managing diabetic retinopathy in India: The India 11-city 9-state study

    PubMed Central

    Gilbert, Clare E.; Babu, R. Giridhara; Gudlavalleti, Aashrai Sai Venkat; Anchala, Raghupathy; Shukla, Rajan; Ballabh, Pant Hira; Vashist, Praveen; Ramachandra, Srikrishna S.; Allagh, Komal; Sagar, Jayanti; Bandyopadhyay, Souvik; Murthy, G. V. S.

    2016-01-01

    Background: There is a paucity of information on the availability of services for diagnosis and management of diabetic retinopathy (DR) in India. Objectives: The study was undertaken to document existing healthcare infrastructure and practice patterns for managing DR. Methods: This cross-sectional study was conducted in 11 cities and included public and private eye care providers. Both multispecialty and stand-alone eye care facilities were included. Information was collected on the processes used in all steps of the program, from how diabetics were identified for screening through to policies about follow-up after treatment by administering a semistructured questionnaire and by using observational checklists. Results: A total of 86 eye units were included (31.4% multispecialty hospitals; 68.6% stand-alone clinics). The availability of a dedicated retina unit was reported by 68.6% (59) facilities. The mean number of outpatient consultations per year was 45,909 per responding facility, with nearly half being new registrations. A mean of 631 persons with sight-threatening-DR (ST-DR) were registered per year per facility. The commonest treatment for ST-DR was laser photocoagulation. Only 58% of the facilities reported having a full-time retina specialist on their rolls. More than half the eye care facilities (47; 54.6%) reported that their ophthalmologists would like further training in retina. Half (51.6%) of the facilities stated that they needed laser or surgical equipment. About 46.5% of the hospitals had a system to track patients needing treatment or for follow-up. Conclusions: The study highlighted existing gaps in service provision at eye care facilities in India. PMID:27144134

  16. 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

  17. Niaspan inhibits diabetic retinopathy-induced vascular inflammation by downregulating the tumor necrosis factor-α pathway

    PubMed Central

    Wang, Yang; Meng, Xiangda; Yan, Hua

    2017-01-01

    Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early DR is characterized by vascular neuroinflammation, cell apoptosis and breakdown of the blood-retinal barrier (BRB). However, optimal treatment options and associated mechanisms remain unclear. Niaspan, which is widely used in the prevention and treatment of hyperlipidemia-associated diseases, has been reported to inhibit inflammation. However, the effects of Niaspan and the mechanisms underlying the anti-inflammatory effects of Niaspan on DR have yet to be reported. The present study aimed to investigate the anti-inflammatory effects and mechanisms of Niaspan in a rat model of DR. Rats with DR exhibited a significant increase in BRB breakdown, retinal apoptosis, and tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) expression. In addition, the expression levels of inducible nitric oxide synthase (iNOS) and intercellular cell adhesion molecule-1 (ICAM-1) were increased in the retinas of DR rats compared with in the normal control group. In conclusion, treatment with Niaspan significantly improved clinical and histopathological outcomes; decreased the expression levels of TNF-α, NF-κB, iNOS and ICAM-1; and decreased apoptosis and BRB breakdown, as compared with in the retinas of DR rats. The present study is the first, to the best of our knowledge, to demonstrate that Niaspan treatment ameliorates DR by inhibiting inflammation, and also suggests that the TNF-α pathway may contribute to the beneficial effects of Niaspan treatment. PMID:28138697

  18. [Eclipse retinopathy].

    PubMed

    Johannessen, Simon; Høgsbro, Malou

    2014-11-10

    Eclipse retinopathy is a condition with macular damage resulting from viewing of a solar eclipse. This case report illustrates how eclipse retinopathy was diagnosed with a delay of more than 30 years. The report also summarises how solar eclipse can be observed without risk of retinal damage.

  19. [Vitrectomy effect on ocular hydrodynamics in proliferative diabetic retinopathy and nonvascular pathology].

    PubMed

    Sdobnikova, S V; Sidamonidze, A L; Kozlova, I V; Troitskaia, N A

    2013-01-01

    The goal of the study was to determine vitrectomy effect on ocular hydrodynamics. Patients were divided into 2 groups: patients with diabetes mellitus (DM) were enrolled in the 1st group, indications for vitrectomy were vitreous hemorrhage or diabetic macula edema. The 2nd group included patients without DM, indications for vitrectomy were macula hole, epiretinal fibrosis. Electronic tonography was used to measure the main ocular hydrodynamic parameters before and 2-12 months after the surgery. Though intraocular pressure (IOP) increased after vitrectomy in all patients, the true IOP was normal in the majority of them (60%) and did not require medical correction. In the rest of cases IOP increase required medical treatment: in 23% during 1 month, in 11% during 6-12 months. In subsequent follow-up during 2 years no glaucoma signs were revealed.

  20. High glucose‐induced changes in hyaloid‐retinal vessels during early ocular development of zebrafish: a short‐term animal model of diabetic retinopathy

    PubMed Central

    Jung, Seung‐Hyun; Kim, Young Sook; Lee, Yu‐Ri

    2015-01-01

    Background and Purpose Although a variety of animal models have been used to test drug candidates and examine the pathogenesis of diabetic retinopathy, time‐saving and inexpensive models are still needed to evaluate the increasing number of therapeutic approaches. Experimental Approach We developed a model for diabetic retinopathy using the early stage of transgenic zebrafish (flk:EGFP) by treating embryos with 130 mM glucose, from 3‐6 days post fertilisation (high‐glucose model). On day 6, lenses from zebrafish larvae were isolated and treated with 3% trypsin, and changes in hyaloid‐retinal vessels were analysed using fluorescent stereomicroscopy. In addition, expression of tight junction proteins (such as zonula occludens‐1), effects of hyperosmolar solutions and of hypoxia, and Vegf expression were assessed by RT –PCR. NO production was assessed with a fluorescent substrate. Effects of inhibitors of the VEGF receptor, NO synthesis and a VEGF antibody (ranibizumab) were also measured. Key Results In this high‐glucose model, dilation of hyaloid‐retinal vessels, on day 6, was accompanied by morphological lesions with disruption of tight junction proteins, overproduction of Vegf mRNA and increased NO production. Treatment of this high‐glucose model with an inhibitor of VEGF receptor tyrosine kinase or an inhibitor of NO synthase or ranibizumab decreased dilation of hyaloid‐retinal vessels. Conclusions and Implications These findings suggest that short‐term exposure of zebrafish larvae to high‐glucose conditions could be used for screening and drug discovery for diabetic retinopathy and particularly for disorders of retinal vessels related to disruption of tight junction proteins and excessive VEGF and NO production. PMID:26276677

  1. The effect of laser pan-retinal photocoagulation with or without intravitreal bevacizumab injections on the OCT-measured macular choroidal thickness of eyes with proliferative diabetic retinopathy

    PubMed Central

    Preti, Rony C; Mutti, Anibal; Ferraz, Daniel A; Zacharias, Leandro C; Nakashima, Yoshitaka; Takahashi, Walter Y; Monteiro, Mario L R

    2017-01-01

    OBJECTIVES: To investigate the effect of laser pan-retinal photocoagulation with or without intravitreal bevacizumab injections on macular choroidal thickness parameters in eyes with high-risk proliferative diabetic retinopathy. METHODS: High-risk proliferative diabetic retinopathy patients undergoing laser treatment were prospectively enrolled in this study. One eye was randomly selected for laser treatment combined with bevacizumab injections, study group, whereas the corresponding eye was subjected to laser treatment alone, control group. Spectral-domain optical coherence tomography with enhanced depth imaging was used to measure the macular choroidal thickness prior to and 1 month after treatment. Measurements in both groups were compared. Clinicaltrials.gov: NCT01389505. RESULTS: Nineteen patients (38 eyes) with a mean±standard deviation age of 53.4±9.3 years were evaluated, and choroidal thickness measurements for 15 patients were used for comparison. The greatest measurement before treatment was the subfoveal choroidal thickness (341.68±67.66 μm and 345.79±83.66 μm for the study and control groups, respectively). No significant difference between groups was found in terms of macular choroidal thickness measurements at baseline or after treatment. However, within-group comparisons revealed a significant increase in choroidal thickness parameters in 10 measurements in the study group and in only 5 temporal measurements in the control group when 1-month follow-up measurements were compared to baseline values. CONCLUSIONS: The macular choroidal thickness does not appear to be significantly influenced by laser treatment alone but increases significantly when associated with bevacizumab injections in patients with proliferative diabetic retinopathy and macular edema. Because bevacizumab injections reduce short-term laser pan-retinal photocoagulation-induced macular edema, our findings suggest that the choroid participates in its pathogenesis. PMID:28273240

  2. Suppression of angiogenic activity of sera from diabetic patients with non-proliferative retinopathy by compounds of herbal origin and sulindac sulfone.

    PubMed

    Skopinski, Piotr; Szaflik, Jerzy; Duda-Król, Barbara; Nartowska, Jadwiga; Sommer, Ewa; Chorostowska-Wynimko, Joanna; Demkow, Urszula; Skopinska-Rózewska, Ewa

    2004-10-01

    Angiogenesis, the process of new blood vessel formation, is the key event in the mechanism of several pathological processes including diabetic retinopathy. The physiological control of angiogenesis depends on the balance between stimulatory and inhibitory factors. Therefore, a number of anti-angiogenic approaches has been developed, many of them based on the inhibition of the functional activity of pro-angiogenic factors. The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice. Pooled sera from 35 patients with diabetes type 2 and retinopathy were used as pro-angiogenic stimuli. The strongest inhibitory effect was observed for the sulindac sulfone and ursolic acid in the highest concentration of 200 micro g/ml, as well as for the low-dosage concomitant treatment with 2 micro g/ml of epigallocatechin gallate (EGCG, green tea flavanol), ursolic acid (plant-derived triterpenoid), sulindac sulfone and convalamaroside (steroidal saponin). Combination treatment was significantly more effective than monotherapy with medium (20 micro g/ml) or lowest doses of tested compounds. The present study is the first to demonstrate the potent anti-angiogenic effect of the combination therapy comprising of plant-derived extracts and sulindac sulfone, as tested in the in vivo angiogenesis experimental model with sera of non-proliferative diabetic retinopathy patients used as the pro-angiogenic stimuli. We think that it might be the first step toward application of some of these compounds, in the future, in preventive anti-angiogenic therapy of these patients, as well, as in the treatment of later, proliferative stage of this disease.

  3. Prevalence of diabetic retinopathy among 13473 patients with diabetes mellitus in China: a cross-sectional epidemiological survey in six provinces

    PubMed Central

    Song, Yifan; Tao, Liyuan; Qiu, Weiqiang; Lv, Huibin; Jiang, Xiaodan; Zhang, Ming