Oxygen-induced retinopathy induces short-term glial stress and long-term impairment of photoentrainment in mice.

PubMed

Mehdi, Madah Khawn-I-Muhammad; Sage-Ciocca, Dominique; Challet, Etienne; Malan, André; Hicks, David

2014-04-01

Retinopathy of prematurity is a serious potentially blinding disease of pre-term infants. There is extensive vascular remodeling and tissue stress, but data concerning alterations in retinal neurons and glia, and long-term functional sequelae are still incomplete. ROP was induced using the oxygen-induced retinopathy (OIR) mouse model. Postnatal day 7 (P7) 129SVE mice were exposed to hyperoxia (75 ± 0.5 % oxygen) for 5 days, and then returned to normoxia to induce OIR. Exposed animals were euthanized at 5 (P17-OIR) and 14 days (P26-OIR) after return to normal air, together with corresponding age-matched control mice (P17-C and P26-C respectively) raised only in room air. Their retinas were examined by immunohistochemistry using a battery of antibodies against key glial and neuronal proteins. A further group of OIR mice and controls were examined at 10 weeks of age for their ability to re-entrain to changing 12 h light/12 h dark cycles, assayed by wheel-running actimetry. In this protocol, animals were subjected to three successive conditions of 300 lux, 15 lux and 1 lux ambient light intensity coupled with 6 hours of jetlag. Animals were euthanized at 4 months of age and used in immunoblotting for rhodopsin. Compared to P17-C, immunohistochemical staining of P17-OIR sections showed up-regulation of stress-related and glutamate-regulatory proteins in astrocytes and Müller glial cells. In contrast, glial phenotypic expression in P26-OIR retinas largely resembled that in P26-C. There was no loss in total retinal ganglion cells (RGC) at either P17-OIR or P26-OIR compared to corresponding controls, whereas intrinsically photosensitive RGC showed significant decreases, with 375 ± 13/field in P26-OIR compared to 443 ± 30/field in P26-C (p < 0.05). Wheel actimetry performed on control and OIR-treated mice at 4 months demonstrated that animals raised in hyperoxic conditions had impaired photoentrainment at low illuminance of 1 lux, as well as significantly reduced

High or low oxygen saturation and severe retinopathy of prematurity: a meta-analysis.

PubMed

Chen, Minghua L; Guo, Lei; Smith, Lois E H; Dammann, Christiane E L; Dammann, Olaf

2010-06-01

Low oxygen saturation appears to decrease the risk of severe retinopathy of prematurity (ROP) in preterm newborns when administered during the first few weeks after birth. High oxygen saturation seems to reduce the risk at later postmenstrual ages (PMAs). However, previous clinical studies are not conclusive individually. To perform a systematic review and meta-analysis to report the association between severe ROP incidence of premature infants with high or low target oxygen saturation measured by pulse oximetry. Studies were identified through PubMed and Embase literature searches through May 2009 by using the terms "retinopathy of prematurity and oxygen" or "retinopathy of prematurity and oxygen therapy." We selected 10 publications addressing the association between severe ROP and target oxygen saturation measured by pulse oximetry. Using a random-effects model we calculated the summary-effect estimate. We visually inspected funnel plots to examine possible publication bias. Low oxygen saturation (70%-96%) in the first several postnatal weeks was associated with a reduced risk of severe ROP (risk ratio [RR]: 0.48 [95% confidence interval (CI): 0.31-0.75]). High oxygen saturation (94%-99%) at > or = 32 weeks' PMA was associated with a decreased risk for progression to severe ROP (RR: 0.54 [95% CI: 0.35-0.82]). Among preterm infants with a gestational age of < or = 32 weeks, early low and late high oxygen saturation were associated with a reduced risk for severe ROP. We feel that a large randomized clinical trial with long-term developmental follow-up is warranted to confirm this meta-analytic result.

The anatomy of the rat eye with oxygen-induced retinopathy.

PubMed

Akula, James D; Favazza, Tara L; Mocko, Julie A; Benador, Ilan Y; Asturias, Ana L; Kleinman, Michael S; Hansen, Ronald M; Fulton, Anne B

2010-02-01

Prior studies have documented the intertwined developmental courses of retinal blood vessel tortuosity (in fundus photographs) and retinal dysfunction (in electroretinographs) in Sprague-Dawley rat models of retinopathy of prematurity (ROP). Two such models, the "50/10 model" and the "75 model," are named after the oxygen regimens used to induce retinopathy and are characterized by distinct neurovascular courses that span a range of disease severity. In this study of 50/10 and 75 model rats, retinal flatmounts were used to study the full vasculature at postnatal day (P) 15, P19 and P30. In addition, the layers of the neural retina were measured in toluidine blue-stained cross sections. Finally, gross anatomic features of the eye, including axial length, retinal surface area, and the ratio of anterior to posterior axial-lengths were evaluated. Both clock hours of neovascularization (NV) and percent avascular retina (AR) peaked at P19 and resolved by P30. Through P19, NV was found in every 50/10 model rat, but in only 60% of 75 model rats. AR was positively related to NV. All inner layers of the retina (outer plexiform layer through ganglion cell layer) were attenuated in 50/10 model rats but, in the 75 model, no layer differed significantly from that in controls. The eyes in both ROP models were smaller than those of age-matched controls. The ratio of anterior to posterior axial-lengths ranged from 0.45 in controls through 0.37 in the 75 model to 0.32 in the 50/10 model. Thus, eye growth is altered in these rat models of ROP.

Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vavilala, Divya Teja; O’Bryhim, Bliss E.; Ponnaluri, V.K. Chaithanya

2013-09-06

Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation.more » We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.« less

Effect(s) of preterm birth on normal retinal vascular development and oxygen-induced retinopathy in the neonatal rat.

PubMed

Li, Rong; Yang, Xiangmin; Wang, Yusheng; Chu, Zhaojie; Liu, Tao; Zhu, Tong; Gao, Xiang; Ma, Zhen

2013-12-01

Maturity is a critical factor in the pathogenesis of retinopathy of prematurity (ROP). One widely used method for studying this condition is that of oxygen-induced retinopathy (OIR). The general conditions of an OIR term animal, both at the time of birth and following birth, differ from those of the preterm infant. This, to simulate preterm conditions and to provide a basis for further studies on ROP, we investigated the effect(s) of preterm birth on retinal vascularization using the neonatal rat. Sprague-Dawley (SD) rats were delivered preterm by caesarean section on the day 19 of gestation. Term pups were used as controls. On the day of birth, preterm and term pups were housed under conditions of room air or cyclic oxygen. Retinas of pups housed in room air on days 4, 7, 10, 14, 18 and 22, as well as pups housed in oxygen on days 14, 18, and 22 were whole-mounted and stained with isolectin-B4. On day 18, cross-sections of the retina were cut and stained with hematoxylin and eosin for the identification of preretinal neovascular tufts. Images of avascular and neovascular areas were compared using light and fluorescence microscopy. Preterm pups had significantly larger avascular retinal areas than term rats on the various postnatal days. After exposure to cyclic oxygen, preterm pups demonstrated significantly larger avascular (days 14 and 18) and neovascular areas (day 18) compared with term rats. On day 22, residual retinopathy of preterm pups was greater than that of term pups. Preterm birth of rats, which are comparable in their physiology to humans, had negative effects on retinal vascularization. The impaired retinal vascular development and subsequent vasoproliferation resulting from hyperoxia in preterm pups is more severe and enduring.

An elevated level of copper zinc superoxide dismutase fails to prevent oxygen induced retinopathy in mice.

PubMed

Klaeger, C; de Sa, L; Klaeger, A J; Carlson, E J; Good, W V; Epstein, C J

1996-05-01

To determine whether a higher level of copper zinc superoxide dismutase (CuZnSOD) can reduce the severity of oxygen induced retinopathy (OIR) in a mouse model. CuZnSOD transgenic mice with a threefold increase in CuZnSOD activity and control non-transgenic mice were exposed to 90% oxygen for 12 hours a day during the first 5 days of life. After oxygen treatment, all mice were reared in room air for 10 days. Another group of transgenic and non-transgenic mice were kept in room air for 15 days and served as control groups for the oxygen effect. At day 15, all mice were killed and perfused with India ink. The retinas were flat mounted on slides and examined with a light microscope. There was a statistically significant increase in the incidence of OIR in mice exposed to high levels of oxygen, whether or not they were transgenic. However, there was no statistically significant difference in the severity of OIR between oxygen treated transgenic and non-transgenic mice. A threefold higher CuZnSOD activity does not protect against OIR in mice. This is an unexpected finding, since oxygen radicals are considered a major factor causing OIR, and increased CuZnSOD activity has reduced oxygen radical induced damage in several neuronal and non-neuronal systems. The possibility of a damaging role for other radicals not affected by CuZnSOD cannot be excluded.

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

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

PubMed

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.

Fully automated, deep learning segmentation of oxygen-induced retinopathy images

PubMed Central

Xiao, Sa; Bucher, Felicitas; Wu, Yue; Rokem, Ariel; Lee, Cecilia S.; Marra, Kyle V.; Fallon, Regis; Diaz-Aguilar, Sophia; Aguilar, Edith; Friedlander, Martin; Lee, Aaron Y.

2017-01-01

Oxygen-induced retinopathy (OIR) is a widely used model to study ischemia-driven neovascularization (NV) in the retina and to serve in proof-of-concept studies in evaluating antiangiogenic drugs for ocular, as well as nonocular, diseases. The primary parameters that are analyzed in this mouse model include the percentage of retina with vaso-obliteration (VO) and NV areas. However, quantification of these two key variables comes with a great challenge due to the requirement of human experts to read the images. Human readers are costly, time-consuming, and subject to bias. Using recent advances in machine learning and computer vision, we trained deep learning neural networks using over a thousand segmentations to fully automate segmentation in OIR images. While determining the percentage area of VO, our algorithm achieved a similar range of correlation coefficients to that of expert inter-human correlation coefficients. In addition, our algorithm achieved a higher range of correlation coefficients compared with inter-expert correlation coefficients for quantification of the percentage area of neovascular tufts. In summary, we have created an open-source, fully automated pipeline for the quantification of key values of OIR images using deep learning neural networks. PMID:29263301

Protective effect of maternal uteroplacental insufficiency on oxygen-induced retinopathy in offspring: removing bias of premature birth

PubMed Central

Becker, Silke; Wang, Haibo; Yu, Baifeng; Brown, Randy; Han, Xiaokun; Lane, Robert H.; Hartnett, M. Elizabeth

2017-01-01

To address the hypothesis that maternal uteroplacental insufficiency (UPI) increases severity of retinopathy of prematurity, we developed a composite rat model of UPI and oxygen-fluctuations and removed premature birth as a confounding factor. Timed-pregnant Sprague-Dawley dams underwent bilateral uterine artery ligation or anesthesia (control) at e19.5. Full-term pups developed in room air (RA) or an oxygen-induced retinopathy (OIR) model. Isolectin-stained retinal flat-mounts were analyzed for percent of areas of avascular/total retina (AVA) and of intravitreal neovascular/total retina (IVNV). Pup weights and serum and mRNA of liver and kidney VEGF, IGF-1, and erythropoietin (EPO) were determined. Multivariable mixed effects linear regressions and Pearson correlations were performed using STATA14. Postnatal growth restriction occurred in pups in UPI/RA, but not in UPI/OIR. Weight gain was similar between UPI/OIR and control/OIR pups. AVA was reduced and a trend toward reduced IVNV was seen in UPI/OIR compared to control/OIR. No difference in birth weights of UPI/OIR vs. control/OIR pups occurred. Serum and renal IGF-1 and EPO were significantly increased in UPI/OIR compared to control/OIR pups. In the absence of prematurity, UPI increased angiogenic factors in association with reduced OIR severity, suggesting that ischemia from UPI could yield protective angiogenic effects by offspring. PMID:28195189

Inducing a visceral organ to protect a peripheral capillary bed: stabilizing hepatic HIF-1α prevents oxygen-induced retinopathy.

PubMed

Hoppe, George; Lee, Tamara J; Yoon, Suzy; Yu, Minzhong; Peachey, Neal S; Rayborn, Mary; Zutel, M Julieta; Trichonas, George; Au, John; Sears, Jonathan E

2014-06-01

Activation of hypoxia-inducible factor (HIF) can prevent oxygen-induced retinopathy in rodents. Here we demonstrate that dimethyloxaloylglycine (DMOG)-induced retinovascular protection is dependent on hepatic HIF-1 because mice deficient in liver-specific HIF-1α experience hyperoxia-induced damage even with DMOG treatment, whereas DMOG-treated wild-type mice have 50% less avascular retina (P < 0.0001). Hepatic HIF stabilization protects retinal function because DMOG normalizes the b-wave on electroretinography in wild-type mice. The localization of DMOG action to the liver is further supported by evidence that i) mRNA and protein erythropoietin levels within liver and serum increased in DMOG-treated wild-type animals but are reduced by 60% in liver-specific HIF-1α knockout mice treated with DMOG, ii) triple-positive (Sca1/cKit/VEGFR2), bone-marrow-derived endothelial precursor cells increased twofold in DMOG-treated wild-type mice (P < 0.001) but are unchanged in hepatic HIF-1α knockout mice in response to DMOG, and iii) hepatic luminescence in the luciferase oxygen-dependent degradation domain mouse was induced by subcutaneous and intraperitoneal DMOG. These findings uncover a novel endocrine mechanism for retinovascular protection. Activating HIF in visceral organs such as the liver may be a simple strategy to protect capillary beds in the retina and in other peripheral tissues. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Eye drop propranolol administration promotes the recovery of oxygen-induced retinopathy in mice.

PubMed

Dal Monte, Massimo; Casini, Giovanni; la Marca, Giancarlo; Isacchi, Benedetta; Filippi, Luca; Bagnoli, Paola

2013-06-01

The mouse model of oxygen-induced retinopathy (OIR) is a well-established model of retinopathy of prematurity (ROP), characterized by the abnormal formation of new blood vessels, which is similar to ROP. In this model, we have recently shown that subcutaneous (sc) administration of the non-selective beta-adrenergic receptor (β-AR) blocker propranolol ameliorates angiogenic processes in the retina when its effects are evaluated at postnatal day (PD) 17. In the present study, we investigated whether propranolol application as collyrium can promote the recovery of OIR. After propranolol administration on the eye, mice were first tested for retinal concentrations of propranolol as compared with those measured after sc or per os administration. Subsequently, we determined the effects of propranolol ophthalmic solutions, at the optimal dose for delivery, on VEGF, IGF-1, hypoxia-inducible factor (HIF)-1α, signal transducer and activator of transcription 3 (STAT3) and retinal neovascularization as assessed in both the superficial and the deep vascular plexuses. The results showed that 2% topical propranolol has an efficiency (in terms of final propranolol concentration in the retina) comparable to that of 20 mg/kg propranolol sc or per os and significantly higher than those observed with doses and administration routes that are currently used with children. Propranolol ophthalmic solutions reduced VEGF and IGF-1 up-regulation in response to hypoxia and drastically inhibited HIF-1α accumulation and STAT3 phosphorylation. As a result of its inhibitory effects on hypoxia-induced proangiogenic factors, propranolol significantly reduced retinal neovascularization in the superficial but not in the deep vascular plexus. An evaluation of retinal neovascularization at PD21 showed that propranolol was still effective in inhibiting OIR. These findings strengthen the hypothesis that β-AR blockade can efficiently counteract OIR and suggest that topical eye application of

Characterization of Oxygen-Induced Retinopathy in Mice Carrying an Inactivating Point Mutation in the Catalytic Site of ADAM15

PubMed Central

Maretzky, Thorsten; Blobel, Carl P.; Guaiquil, Victor

2014-01-01

Purpose. Retinal neovascularization is found in diseases such as macular degeneration, diabetic retinopathy, or retinopathy of prematurity and is usually caused by alterations in oxygen supply. We have previously described that mice lacking the membrane-anchored metalloproteinase ADAM15 (a Disintegrin and Metalloprotease 15) have decreased pathological neovascularization of the retina in the oxygen-induced retinopathy (OIR) model. The main purpose of the present study was to determine the contribution of the catalytic activity of ADAM15 to OIR. Methods. To address this question, we generated knock-in mice carrying an inactivating Glutamate to Alanine (E>A) point mutation in the catalytic site of ADAM15 (Adam15E>A mice) and subjected these animals to the OIR model and a heterotopic tumor model. Moreover, we used cell-based assays to determine whether ADAM15 can process cell surface receptors involved in angiogenesis. Results. We found that pathological neovascularization in the OIR model in Adam15E>A mice was comparable to that observed in wild type mice, but tumor implantation by heterotopically injected melanoma cells was reduced. In cell-based assays, overexpressed ADAM15 could process the FGFR2iiib, but was unable to process several receptors with roles in angiogenesis. Conclusions. Collectively, these results suggest that the catalytic activity of ADAM15 is not crucial for its function in promoting pathological neovascularization in the mouse OIR model, most likely because of the very limited substrate repertoire of ADAM15. Instead, other noncatalytic functions of ADAM15 must be important for its role in the OIR model. PMID:25249606

Early Detection of Diabetic Retinopathy.

PubMed

Safi, Hamid; Safi, Sare; Hafezi-Moghadam, Ali; Ahmadieh, Hamid

2018-04-18

Diabetic retinopathy (DR) is a primary cause of visual impairment worldwide. Diabetes mellitus may be associated with ophthalmoscopically nonvisible neurovascular damage that progresses before the first clinical signs of DR appear. Reduction of the inner neuroretinal layer thickness on macular optical coherence tomography (OCT), reduced contrast sensitivity primarily at low spatial frequencies, abnormal results in color vision and microperimetry tests, and a prolonged implicit time recorded by multifocal electroretinography have been proposed for detection of early functional and nonvisible structural neuroretinal changes. Vascular abnormalities such as changes in the retinal vessels caliber, architectural indices, and blood flow have been investigated to evaluate the early stages of DR. The results of OCT angiography, retinal vessel oxygen saturation patterns, and elevated levels of circulating blood markers and cytokines have been suggested as early signs of DR. Light-based molecular imaging in rodents has been developed to demonstrate changes in protein expressions in the retinal microvessels as diagnostic biomarkers. Future clinical studies will examine the safety and efficacy of this approach in humans. We summarize all studies related to subclinical DR biomarkers. Copyright © 2018 Elsevier Inc. All rights reserved.

Early diagnosis of diabetic retinopathy in primary care.

PubMed

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

2015-01-01

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. 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. 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. 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.

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

Retinopathy of prematurity and induced changes in arterial oxygen saturation with near infrared spectrophotometry: a retrospective cohort study

NASA Astrophysics Data System (ADS)

von Siebenthal, K.; Keel, M.; Dietz, V.; Fauchere, J. C.; Martin, X.; Wolf, Martin; Duc, G.; Bucher, H. U.

1996-10-01

Near-infrared spectrophotometry (NIRS) is a noninvasive method for measuring oxygenated and deoxygenated hemoglobin in the neonatal brain. Using oxygen as a tracer, it is possible to calculate cerebral blood flow (cbf) and hemoglobin concentration (cHbc), which corresponds to cerebral blood volume, by inducing small changes in arterial oxygen saturation. Variability of tcpO2 is considered to be associated with severe retinopathy of prematurity (ROP). A preliminary analysis without control found a 51 percent incidence of ROP in infants subjected to NIRS measurements whereas among infants who were not exposed to oxygen changes, only 29 percent developed ROP. A controlled study with matched pairs was performed. Thirty-nine premature newborns who had received NIRS recordings were matched with 39 out of 172 infants who had not received NIRS. Using this controlled study design there was no difference in the incidence and severity of ROP between the two groups. The conclusions are that: 1) small changes in oxygen saturation of 3 to 10 percent to measure cbf and cHbc did not increase the incidence or the degree of severity of ROP. 2) A controlled study design is important. Analyses of uncontrolled data would have led to the conclusion that oxygen changes as used with NIRS increase the risk of ROP.

Adenosine receptors and caffeine in retinopathy of prematurity.

PubMed

Chen, Jiang-Fan; Zhang, Shuya; Zhou, Rong; Lin, Zhenlang; Cai, Xiaohong; Lin, Jing; Huo, Yuqing; Liu, Xiaoling

2017-06-01

Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants. Notably, cellular responses to hypoxia are characterized by robust increases in extracellular adenosine production and the markedly induced adenosine receptors, which provide a novel target for preferential control of pathological angiogenesis without affecting normal vascular development. Here, we review the experimental evidence in support of adenosine receptor-based therapeutic strategy for ROP, including the aberrant adenosine signaling in oxygen-induced retinopathy and the role of three adenosine receptor subtypes (A 1 R, A 2A R, A 2B R) in development and treatment of ROP using oxygen-induced retinopathy models. The clinical and initial animal evidence that implicate the therapeutic effect of caffeine (a non-selective adenosine receptor antagonist) in treatment of ROP are highlighted. Lastly, we discussed the translational potential as well therapeutic advantage of adenosine receptor- and caffeine-based therapy for ROR and possibly other proliferative retinopathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adenosine receptors and caffeine in retinopathy of prematurity

PubMed Central

Chen, Jiang-Fan; Zhang, Shuya; Zhou, Rong; Lin, Zhenlang; Cai, Xiaohong; Lin, Jing; Huo, Yuqing; Liu, Xiaoling

2017-01-01

Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants. Notably, cellular responses to hypoxia are characterized by robust increases in extracellular adenosine production and the markedly induced adenosine receptors, which provide a novel target for preferential control of pathological angiogenesis without affecting normal vascular development. Here, we review the experimental evidence in support of adenosine receptor-based therapeutic strategy for ROP, including the aberrant adenosine signaling in oxygen-induced retinopathy and the role of three adenosine receptor subtypes (A1R, A2AR, A2BR) in development and treatment of ROP using oxygen-induced retinopathy models. The clinical and initial animal evidence that implicate the therapeutic effect of caffeine (a non-selective adenosine receptor antagonist) in treatment of ROP are highlighted. Lastly, we discussed the translational potential as well therapeutic advantage of adenosine receptor- and caffeine-based therapy for ROR and possibly other proliferative retinopathy. PMID:28088487

Retinopathy of prematurity

PubMed Central

Hellström, Ann; Smith, Lois E H; Dammann, Olaf

2015-01-01

The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal–fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ω-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development. PMID:23782686

Quantitative assessment of early diabetic retinopathy using fractal analysis.

PubMed

Cheung, Ning; Donaghue, Kim C; Liew, Gerald; Rogers, Sophie L; Wang, Jie Jin; Lim, Shueh-Wen; Jenkins, Alicia J; Hsu, Wynne; Li Lee, Mong; Wong, Tien Y

2009-01-01

Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber. Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

AMA0428, A Potent Rock Inhibitor, Attenuates Early and Late Experimental Diabetic Retinopathy.

PubMed

Hollanders, Karolien; Hove, Inge Van; Sergeys, Jurgen; Bergen, Tine Van; Lefevere, Evy; Kindt, Nele; Castermans, Karolien; Vandewalle, Evelien; van Pelt, Jos; Moons, Lieve; Stalmans, Ingeborg

2017-02-01

Diabetic retinopathy (DR) is characterized by an early stage of inflammation and vessel leakage, and an advanced vasoproliferative stage. Also, neurodegeneration might play an important role in disease pathogenesis. The aim of this study was to investigate the effect of the Rho kinase (ROCK) inhibitor, AMA0428, on these processes. The response to ROCK inhibition by AMA0428 (1 µg) was studied in vivo using the murine model for streptozotocin (STZ)-induced diabetes, focusing on early non-proliferative DR features and the oxygen-induced retinopathy (OIR) model to investigate proliferative DR. Intravitreal (IVT) administration of AMA0428 was compared with murine anti-VEGF-R2 antibody (DC101, 6.2 µg) and placebo (H 2 O/PEG; 1C8). Outcome was assessed by analyzing leukostasis using fluorescein isothiocyanate coupled concanavalin A (FITC-ConA) and vessel leakage (bovine serum albumin conjugated with fluorescein isothiocyanate; FITC-BSA)/neovascularization and neurodegeneration by immunohistological approaches (hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), Brn3a). ELISA and Western blotting were employed to unravel the consequences of ROCK inhibition (1 µM AMA0428) on myosin phosphatase target protein (MYPT)-1 phosphorylation, endothelial nitric oxide synthase (eNOS) phosphorylation, and vascular endothelial growth factor (VEGF) levels in retinas of diabetic mice, on NF-κβ activity and ICAM-1 expression in endothelial cells (ECs). In vivo, AMA0428 significantly reduced vessel leakage and neovascularization, respectively, in the STZ and OIR model, comparable to DC101 therapy. Additionally, the ROCK inhibitor decreased neurodegeneration in both models and inhibited leukostasis by 30% (p < 0.05) in the STZ model (p < 0.05), while DC101 had no positive effect on the outcome of these latter processes. ROCK activity was upregulated in the diabetic retina and AMA0428 administration resulted in

Anti-angiogenic and anti-inflammatory effect of Magnolol in the oxygen-induced retinopathy model.

PubMed

Yang, Boyu; Xu, Yue; Yu, Shanshan; Huang, Yongsheng; Lu, Lin; Liang, Xiaoling

2016-01-01

In the present study, we investigated the effects of Magnolol on the retinal neovascularization (RNV) and local glial cells in an oxygen-induced retinopathy (OIR) model and explored their molecular mechanisms. Neonatal C57BL/6J mice were subjected to 75% O2 ± 5% from postnatal day (P) 7 to P12 and subsequently returned to room air. Mice were injected with 25 mg/kg Magnolol intraperitoneally once a day from P12 to P17, then retinas were harvested and flat-mounted to assess the retinal vessels, astrocytes and microglia. To clarify the molecular mechanisms of Magnolol, we observed the level of inflammatory cytokines such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, and analyzed the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway in OIR mice. Intraperitoneal administration of Magnolol resulted in significant reduction of RNV without retinal toxicity or perturbation of developmental retinal angiogenesis. In addition, Magnolol preserved the astrocyte morphology and diminished the activation of microglia. Moreover, Magnolol down regulated the expression of inflammatory cytokines and inactivated the HIF-1α/VEGF pathway. These results indicated that Magnolol might have potential for the treatment of pathological retinal angiogenesis and glial dysfunctions via anti-inflammation and inhibition of HIF-1α/VEGF pathway.

Vascular changes on fluorescein angiography of premature infants with low risk of retinopathy of prematurity after high oxygen exposure.

PubMed

Martinez-Castellanos, Maria Ana; Velez-Montoya, Raul; Price, Kenneth; Henaine-Berra, Andree; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Cernichiaro-Espinosa, Linda Alejandra

2017-01-01

To describe a wide array of peripheral vascular changes using fluorescein angiography in preterm neonates, without high risk characteristics for developing retinopathy of prematurity, that were exposed to high oxygen concentration. Retrospective, two center, case series. Newborns at two different hospitals with ≥1500 g or gestational age of ≥32 weeks, fluorescein angiography performed, and with high oxygen exposure without adequate control were included. 294 infants diagnosed with ROP were analyzed. Only 28 eyes from 14 patients with peripheral vascular abnormalities in older and heavier babies were included. Two distinct type of peripheral vascular changes were observed: group 1 or non-proliferative: areas of capillary non-perfusion along with widespread arteriovenous shunting between adjacent primary vessels, tortuosity of primary vessels, abnormal budding of tertiary vessels and capillaries, abnormal capillary tufts and absence of foveal avascular zone; group 2 or proliferative: all of the characteristics of group 1 plus leakage of dye from the boundary between perfused and non-perfused retina and/or optic disc. Peripheral vascular abnormalities different from retinopathy of prematurity are observed in older than 32 weeks of gestational age, and heavier than 1500 g babies. This makes the authors classify these patients as having a disease caused solely by oxygen dysregulation at the neonatal intensive care unit similarly to the oxygen induced retinopathy in experimental studies.

Retinopathy predicts progression of fasting plasma glucose: An Early Diabetes Intervention Program (EDIP) Analysis

PubMed Central

Patel, Yash R.; Kirkman, M. Sue; Considine, Robert V; Hannon, Tamara S; Mather, Kieren J

2017-01-01

Background Retinopathy is increasingly recognized in prediabetic populations, and may herald increased risk of metabolic worsening. The Early Diabetes Intervention Program (EDIP) evaluated worsening of glycemia in screen-detected Type 2 diabetes, following participants for up to 5 years. Here we have evaluated whether the presence of retinopathy at the time of detection of diabetes was associated with accelerated progression of glycemia. Methods We prospectively studied 194 participants from EDIP with available baseline retinal photographs. Retinopathy was determined at baseline using 7-field fundus photography and defined as an Early Treatment of Diabetic Retinopathy Study Scale grading score of ≥20. Results At baseline, 12% of participants had classical retinal lesions indicating retinopathy. In univariate Cox proportional hazard analysis, the presence of retinopathy at baseline was associated with a doubled risk of progression of fasting plasma glucose (HR 2.02; 95% CI 1.05–3.89). The retinopathy effect was robust to individual adjustment for age and glucose, the most potent determinants of progression in EDIP. Conclusion Retinopathy was associated with increased risk of progression of fasting plasma glucose among adults with screen-detected, early diabetes. Early detection of retinopathy may help individualize more aggressive therapy to prevent progressive metabolic worsening in early diabetes. PMID:28003103

Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy.

PubMed

Fondi, Klemens; Wozniak, Piotr A; Howorka, Kinga; Bata, Ahmed M; Aschinger, Gerold C; Popa-Cherecheanu, Alina; Witkowska, Katarzyna J; Hommer, Anton; Schmidl, Doreen; Werkmeister, René M; Garhöfer, Gerhard; Schmetterer, Leopold

2017-08-01

The aim of this study was to compare retinal oxygen extraction in individuals with diabetes with no or mild non-proliferative diabetic retinopathy and healthy age- and sex-matched volunteers. A total of 24 participants with type 1 diabetes and 24 healthy age- and sex-matched volunteers were included in this cross-sectional study. Retinal oxygen extraction was measured by combining total retinal blood flow measurements using a custom-built bi-directional Doppler optical coherence tomography system with measurements of oxygen saturation using spectroscopic reflectometry. Based on previously published mathematical modelling, the oxygen content in retinal vessels and total retinal oxygen extraction were calculated. Total retinal blood flow was higher in diabetic participants (46.4 ± 7.4 μl/min) than in healthy volunteers (40.4 ± 5.3 μl/min, p = 0.002 between groups). Oxygen content in retinal arteries was comparable between the two groups, but oxygen content in retinal veins was higher in participants with diabetes (0.15 ± 0.02 ml O 2 /ml) compared with healthy control participants (0.13 ± 0.02 ml O 2 /ml, p < 0.001). As such, the arteriovenous oxygen difference and total retinal oxygen extraction were reduced in participants with diabetes compared with healthy volunteers (total retinal oxygen extraction 1.40 ± 0.44 vs 1.70 ± 0.47 μl O 2 /min, respectively, p = 0.03). Our data indicate early retinal hypoxia in individuals with type 1 diabetes with no or mild diabetic retinopathy as compared with healthy control individuals. Further studies are required to fully understand the potential of the technique in risk stratification and treatment monitoring. ClinicalTrials.gov NCT01843114.

Arginase in Retinopathy

PubMed Central

Narayanan, S. Priya; Rojas, Modesto; Suwanpradid, Jutamas; Toque, Haroldo A.; Caldwell, R. William; Caldwell, Ruth B.

2013-01-01

Ischemic retinopathies, such as diabetic retinopathy (DR), retinopathy of prematurity and retinal vein occlusion are a major cause of blindness in developed nations worldwide. Each of these conditions is associated with early neurovascular dysfunction. However, conventional therapies target clinically significant macula edema or neovascularization, which occur much later. Intraocular injections of anti-VEGF show promise in reducing retinal edema, but the effects are usually transient and the need for repeated injections increases the risk of intraocular infection. Laser photocoagulation can control pathological neovascularization, but may impair vision and in some patients the retinopathy continues to progress. Moreover, neither treatment targets early stage disease or promotes repair. This review examines the potential role of the ureahydrolase enzyme arginase as a therapeutic target for the treatment of ischemic retinopathy. Arginase metabolizes L-arginine to form proline, polyamines and glutamate. Excessive arginase activity reduces the L-arginine supply for nitric oxide synthase (NOS), causing it to become uncoupled and produce superoxide and less NO. Superoxide and NO react and form the toxic oxidant peroxynitrite. The catabolic products of polyamine oxidation and glutamate can induce more oxidative stress and DNA damage, both of which can cause cellular injury. Studies indicate that neurovascular injury during retinopathy is associated with increased arginase expression/activity, decreased NO, polyamine oxidation, formation of superoxide and peroxynitrite and dysfunction and injury of both vascular and neural cells. Furthermore, data indicate that the cytosolic isoform arginase I (AI) is involved in hyperglycemia-induced dysfunction and injury of vascular endothelial cells whereas the mitochondrial isoform arginase II (AII) is involved in neurovascular dysfunction and death following hyperoxia exposure. Thus, we postulate that activation of the arginase

SDF-1 is both necessary and sufficient to promote proliferative retinopathy

PubMed Central

Butler, Jason M.; Guthrie, Steven M.; Koc, Mehmet; Afzal, Aqeela; Caballero, Sergio; Brooks, H. Logan; Mames, Robert N.; Segal, Mark S.; Grant, Maria B.; Scott, Edward W.

2005-01-01

Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell–derived factor–1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen–4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell–derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy. PMID:15630447

Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy.

PubMed

Zheng, Ling; Howell, Scott J; Hatala, Denise A; Huang, Kun; Kern, Timothy S

2007-02-01

It has been previously reported that aspirin inhibited the development of diabetic retinopathy in diabetic animals, raising the possibility that anti-inflammatory drugs may have beneficial effects on diabetic retinopathy. To further explore this, we compared effects of oral consumption of three different salicylate-based drugs (aspirin, sodium salicylate, and sulfasalazine) on the development of early stages of diabetic retinopathy in rats. These three drugs differ in their ability to inhibit cyclooxygenase but share an ability to inhibit nuclear factor-kappaB (NF-kappaB). Diabetes of 9-10 months duration significantly increased the number of TUNEL (transferase-mediated dUTP nick-end labeling)-positive capillary cells and acellular (degenerate) capillaries in the retinal vasculature, and all three salicylate-based drugs inhibited this cell death and formation of acellular capillaries without altering the severity of hyperglycemia. In short-term diabetes (2-4 months), all three salicylates inhibited the diabetes-induced loss of neuronal cells from the ganglion cell layer. Oral aspirin (as a representative of the salicylate family) inhibited diabetes-induced increase in NF-kappaB DNA-binding affinity in electrophoretic mobility shift assay and transcription factor array in nuclear extract isolated from whole retina. All three salicylates inhibited the diabetes-induced translocation of p50 (a subunit of NF-kappaB) into nuclei of retinal vascular endothelial cells of the isolated retinal vasculature, as well as of p50 and p65 into nuclei of cells in the ganglion cell layer and inner nuclear layer on whole-retinal sections. Sulfasalazine (also as a representative of the salicylates) inhibited the diabetes-induced upregulation of several inflammatory gene products, which are regulated by NF-kappaB, including vascular cell adhesion molecule, intracellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2 in whole-retinal lysate. Salicylates, in

Retinopathy of prematurity: molecular pathology and therapeutic strategies.

PubMed

Mechoulam, Hadas; Pierce, Eric A

2003-01-01

Retinopathy of prematurity (ROP) is an ischemia-induced proliferative retinopathy, which affects premature infants with low birth weight. It is a leading cause of visual impairment and blindness in children, and shares pathophysiological characteristics with other common ocular diseases such as diabetic retinopathy, central vein occlusion, and age-related macular degeneration. Pathologically similar inherited diseases such as Norrie disease suggest a possible genetic component in the susceptibility to ROP. The process of retinal neovascularization in ROP and in animal models of oxygen-induced retinopathy is complex, and involves angiogenic factors, such as vascular endothelial growth factor, and basement membrane components. Potential medical therapies for ROP, including modulators of angiogenic factors, inhibitors of basement membrane changes, endogenous inhibitors such as pigment epithelium derived factor, and anti-inflammatory drugs, have shown efficacy against neovascularization in several animal models. Some of these therapies are in clinical trials now for diabetic retinopathy and age-related macular degeneration, and in the future may prove efficacious for the treatment of ROP.

The effect of autoimmune retinopathy on retinal vessel oxygen saturation.

PubMed

Waizel, Maria; Türksever, Cengiz; Todorova, Margarita G

2018-05-22

To study the retinal vessel oxygen saturation alterations in patients with autoimmune retinopathy (AIR) and patients with autoimmune retinopathy associated with retinitis pigmentosa (AIR-RP) in comparison with healthy controls and patients with isolated retinitis pigmentosa (RP). Prospective, cross-sectional, and non-interventional study. Retinal vessel oximetry (RO) was performed on a total of 139 eyes: six eyes suffering from AIR and four eyes with AIR-RP were compared to 59 healthy control eyes and to 70 eyes with RP. A computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to evaluate retinal vessel oxygen saturation. The mean oxygen saturation in the first and second branch retinal arterioles (A-SO 2 ) and venules (V-SO 2 ) were measured and their difference (A-V SO 2 ) was calculated. In addition, we measured the diameter of the retinal arterioles (D-A) and venules (D-V). Oxygen metabolism is altered in patients with isolated AIR and AIR-RP. Both, AIR and AIR-RP groups, differed from healthy controls showing significantly higher V-SO 2 values and significantly lower A-V SO 2 values (p < 0.025). In addition, the AIR-RP group could be differentiated from eyes suffering from isolated RP by means of significantly higher V-SO 2 values. Comparing retinal vessel diameters, both, the AIR and AIR-RP groups, presented with significant arterial (p = 0.05) and venular (p < 0.03) vessel attenuation than the healthy control group. Based on our results, in analogy to patients suffering from RP, oxygen metabolism seems to be altered in AIR patients.

Silencing of galectin-1 inhibits retinal neovascularization and ameliorates retinal hypoxia in a murine model of oxygen-induced ischemic retinopathy.

PubMed

Yang, Ning; Zhang, Wenxi; He, Tao; Xing, Yiqiao

2017-06-01

Aberrant neovascularization is a consequence of inappropriate angiogenic signaling and contributes to several diseases. Although many regulators of pathogenic angiogenesis have been identified, the understanding of this process remains incomplete. Galectin-1 (Gal-1), as a homodimeric protein with a single carbohydrate-recognition domain, is implicated in several pathologic processes, including angiogenesis; however, its involvement in retinal neovascularization (RNV) remains unknown. Here, we investigated the anti-angiogenic effect of silencing Gal-1 through intravitreal injection in a mouse model of oxygen-induced retinopathy (OIR). Our results revealed that Gal-1 was overexpressed and closely related to retinal neo-vessels in OIR retinas. After silencing Gal-1 via intravitreal injection of adenoviral-Gal-1-RNA interference (Ad-Gal-1-RNAi), RNV and retinal hypoxia were significantly attenuated, indicating the anti-angiogenic effect of Gal-1 inhibition. Western blot analysis and real-time polymerase chain reaction indicated that the expression of both neuropilin-1 (Nrp-1) and B cell lymphoma-2 (Bcl-2) decreased after intravitreal injection of Ad-Gal-1-RNAi, implying the possible involvement of Nrp-1 and Bcl-2 in Gal-1-related angiogenic processes. Additionally, whole-mount fluorescence and hematoxylin and eosin staining showed that intravitreal injection of Ad-Gal-1-RNAi did not significantly disrupt the retinal vasculature and neuronal structure of room air mice. Moreover, Ad-Gal-1-RNAi transfer promoted retinal vascular sprouting and increased retinal vascular perfusion, likely through decreased phosphorylation of myosin phosphatase target protein-1. Collectively, our results demonstrated that Gal-1 functions as an important regulator in RNV and offers a promising strategy for the treatment of RNV diseases, such as proliferative diabetic retinopathy and retinopathy of prematurity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats.

PubMed

Beharry, Kay D; Cai, Charles L; Skelton, Jacqueline; Siddiqui, Faisal; D'Agrosa, Christina; Calo, Johanna; Valencia, Gloria B; Aranda, Jacob V

2018-05-01

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O₂) with brief hypoxia (12% O₂); (2) RA with 12% O₂; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O₂ resolution. Interventions and initiatives to curtail O₂ variations should remain a high priority to prevent severe retinopathy.

Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats

PubMed Central

Cai, Charles L.; Skelton, Jacqueline; Siddiqui, Faisal; D’Agrosa, Christina; Calo, Johanna; Valencia, Gloria B.; Aranda, Jacob V.

2018-01-01

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O2) with brief hypoxia (12% O2); (2) RA with 12% O2; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O2 resolution. Interventions and initiatives to curtail O2 variations should remain a high priority to prevent severe retinopathy. PMID:29724000

A machine learning approach for automated assessment of retinal vasculature in the oxygen induced retinopathy model.

PubMed

Mazzaferri, Javier; Larrivée, Bruno; Cakir, Bertan; Sapieha, Przemyslaw; Costantino, Santiago

2018-03-02

Preclinical studies of vascular retinal diseases rely on the assessment of developmental dystrophies in the oxygen induced retinopathy rodent model. The quantification of vessel tufts and avascular regions is typically computed manually from flat mounted retinas imaged using fluorescent probes that highlight the vascular network. Such manual measurements are time-consuming and hampered by user variability and bias, thus a rapid and objective method is needed. Here, we introduce a machine learning approach to segment and characterize vascular tufts, delineate the whole vasculature network, and identify and analyze avascular regions. Our quantitative retinal vascular assessment (QuRVA) technique uses a simple machine learning method and morphological analysis to provide reliable computations of vascular density and pathological vascular tuft regions, devoid of user intervention within seconds. We demonstrate the high degree of error and variability of manual segmentations, and designed, coded, and implemented a set of algorithms to perform this task in a fully automated manner. We benchmark and validate the results of our analysis pipeline using the consensus of several manually curated segmentations using commonly used computer tools. The source code of our implementation is released under version 3 of the GNU General Public License ( https://www.mathworks.com/matlabcentral/fileexchange/65699-javimazzaf-qurva ).

Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity.

PubMed

Fu, Zhongjie; Meng, Steven S; Burnim, Samuel B; Smith, Lois Eh; Lo, Amy Cy

2017-07-01

Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. Mouse pups were exposed to 75% oxygen for 5 days and returned to room air for another 5 days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy.

PubMed

Ometto, Giovanni; Assheton, Phil; Calivá, Francesco; Chudzik, Piotr; Al-Diri, Bashir; Hunter, Andrew; Bek, Toke

2017-12-01

Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy.

Secretoneurin, substance P and neuropeptide Y in the oxygen-induced retinopathy in C57Bl/6N mice.

PubMed

Schmid, Eduard; Nogalo, Marina; Bechrakis, Nikolaos E; Fischer-Colbrie, Reiner; Tasan, Ramon; Sperk, Günther; Theurl, Markus; Beer, Arno G E; Kirchmair, Rudolf; Herzog, Herbert; Troger, Josef

2012-10-01

In this study, we investigated whether the proangiogenic neuropeptides secretoneurin (SN), substance P (SP), and neuropeptide Y (NPY) contribute to the development of abnormal neovascularization in the oxygen-induced retinopathy (OIR) model in mice. By exposing litters of C57Bl/6N mice to 75% oxygen from postnatal day 7 (P7) until postnatal day 11 (P11) and then returning them to normoxic conditions, retinal ischemia and subsequent neovascularization on the retinal surface were induced. Retinae were dissected on P9, P11, P12-P14, P16 and P20, and the concentrations of SN, SP, NPY and VEGF determined by radioimmunoassay or ELISA. The levels of SN and SP increased in controls from P9 until P16 and from P9 until P14, respectively, whereas the levels of NPY were high at P9 and decreased thereafter until P20, suggesting that NPY may participate in the development of the retina. However, dipeptidyl peptidase IV (DPPIV) and the NPY-Y2 receptor were not detectable in the immature retina indicating that NPY is not involved in the physiological vascularization in the retina. Compared to controls, OIR had no effect on the levels of SN, whereas levels of both SP and NPY slightly decreased during hyperoxia. Normalization of the levels of SP, and to a more pronounced extent of NPY, was significantly delayed during relative hypoxia. This clearly indicates that these three neuropeptides are not involved in the pathogenesis of neovascularization in OIR. Moreover, since there were no differences in the expression of two vessel markers in the retina of NPY knockout mice versus controls at P14, NPY is also not involved in the delayed development of the intermediate and deep vascular plexus in the retina in this animal model. Copyright © 2012 Elsevier Inc. All rights reserved.

Lack of differences in the regional variation of oxygen saturation in larger retinal vessels in diabetic maculopathy and proliferative diabetic retinopathy.

PubMed

Jørgensen, Christina Mørup; Bek, Toke

2017-06-01

Diabetic retinopathy is characterised by morphological lesions in the ocular fundus related to disturbances in retinal blood flow. The two vision threatening forms of retinopathy show specific patterns of distribution of retinal lesions with proliferative diabetic retinopathy (PDR) developing secondary to ischaemia and hypoxia in the retinal periphery and diabetic maculopathy (DM) developing secondary to hyperperfusion and increased vascular permeability in the macular area. These differences in the distribution of retinal lesions might be reflected in regional differences in oxygen saturation in the larger retinal vessels. Dual-wavelength retinal oximetry was performed in 30 normal persons, 30 patients with DM and 30 patients with PDR, and the oxygen saturation was measured in peripapillary vessels supplying the four retinal quadrants and in branches from the upper temporal arcades supplying, respectively, the macular area and the retinal periphery. The overall oxygen saturation was significantly higher in diabetic patients than in normal persons and the arteriovenous (AV) saturation difference significantly lower in the patients with DM. The regional variation in oxygen saturation was similar in the three studied groups with a decreasing saturation from the upper nasal through the lower nasal, lower temporal and the upper temporal peripapillary vessels, and with a significantly higher oxygen saturation in venules draining the macular area than in venules draining the retinal periphery. The regional differences in retinal lesions in vision threatening diabetic retinopathy are not reflected in regional differences in the oxygen saturation of larger retinal vessels. The development of vision threatening diabetic retinopathy depends on other factors, such as, for example, regional differences in the retinal microcirculation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies.

PubMed

Holmström, Gerd; van Wijngaarden, Peter; Coster, Douglas J; Williams, Keryn A

2007-12-01

Despite advances in management and treatment, retinopathy of prematurity remains a major cause of childhood blindness. Evidence for a genetic basis for susceptibility to retinopathy of prematurity is examined, including the influences of sex, ethnicity, and ocular pigmentation. The role of polymorphisms is explored in the genes for vascular endothelial growth factor and insulin-like growth factor-1, and of mutations in the Norrie disease gene. Insights into the genetic basis of retinopathy of prematurity provided by the animal model of oxygen induced retinopathy are examined. Evidence for a genetic component for susceptibility to retinopathy of prematurity is strong, although the molecular identity of the gene or genes involved remains uncertain.

Early visual cortical structural changes in diabetic patients without diabetic retinopathy.

PubMed

Ferreira, Fábio S; Pereira, João M S; Reis, Aldina; Sanches, Mafalda; Duarte, João V; Gomes, Leonor; Moreno, Carolina; Castelo-Branco, Miguel

2017-11-01

It is known that diabetic patients have changes in cortical morphometry as compared to controls, but it remains to be clarified whether the visual cortex is a disease target, even when diabetes complications such as retinopathy are absent. Therefore, we compared type 2 diabetes patients without diabetic retinopathy with control subjects using magnetic resonance imaging to assess visual cortical changes when retinal damage is not yet present. We performed T1-weighted imaging in 24 type 2 diabetes patients without diabetic retinopathy and 27 age- and gender-matched controls to compare gray matter changes in the occipital cortex between groups using voxel based morphometry. Patients without diabetic retinopathy showed reduced gray matter volume in the occipital lobe when compared with controls. Reduced gray matter volume in the occipital cortex was found in diabetic patients without retinal damage. We conclude that cortical early visual processing regions may be affected in diabetic patients even before retinal damage occurs.

Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy.

PubMed

Blom, Jan J; Giove, Thomas J; Favazza, Tara L; Akula, James D; Eldred, William D

2011-06-01

The nitric oxide (NO) signaling pathway is integrally involved in visual processing and changes in the NO pathway are measurable in eyes of diabetic patients. The small peptide adrenomedullin (ADM) can activate a signaling pathway to increase the enzyme activity of neuronal nitric oxide synthase (nNOS). ADM levels are elevated in eyes of diabetic patients and therefore, ADM may play a role in the pathology of diabetic retinopathy. The goal of this research was to test the effects of inhibiting the ADM/NO signaling pathway in early diabetic retinopathy. Inhibition of this pathway decreased NO production in high-glucose retinal cultures. Treating diabetic mice with the PKC β inhibitor ruboxistaurin for 5 weeks lowered ADM mRNA levels and ADM-like immunoreactivity and preserved retinal function as assessed by electroretinography. The results of this study indicate that inhibiting the ADM/NO signaling pathway prevents neuronal pathology and functional losses in early diabetic retinopathy.

Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

PubMed

Inomata, Kei; Taniguchi, Shinji; Yonemoto, Hiroki; Inoue, Takeshi; Kawase, Akihiko; Kondo, Yuichi

2016-11-01

Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO 2 ) target range (85-92%) from April 2011. Lower SpO 2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO 2 target range, during the early postnatal stage, increases the risk of DA closure failure. Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. © 2016 Japan Pediatric Society.

The progress of prophylactic treatment in retinopathy of prematurity

PubMed Central

Zhang, Hong-Bing; Wang, Xiao-Dong; Xu, Kun; Li, Xiao-Gang

2018-01-01

Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4 to 6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about, 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR; a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future. PMID:29862189

Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity

PubMed Central

Hoppe, George; Yoon, Suzy; Gopalan, Banu; Savage, Alexandria R.; Brown, Rebecca; Case, Kelsey; Vasanji, Amit; Chan, E. Ricky; Silver, Randi B.; Sears, Jonathan E.

2016-01-01

Retinopathy of prematurity (ROP) causes 100,000 new cases of childhood blindness each year. ROP is initiated by oxygen supplementation necessary to prevent neonatal death. We used organ systems pharmacology to define the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, ROP model) by hypoxia-inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarate analog dimethyloxalylglycine (DMOG). Although both molecules conferred a protective phenotype, gene expression analysis by RNA sequencing found that Roxadustat can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilization and increased serum angiokines. As predicted by pathway analysis, Roxadustat rescued the hepatic HIF-1 knockout mouse from retinal oxygen toxicity, whereas DMOG could not. The simplicity of systemic treatment that targets both the liver and the eye provides a rationale for protecting the severely premature infant from oxygen toxicity. PMID:27091985

Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies

PubMed Central

Holmström, Gerd; van Wijngaarden, Peter; Coster, Douglas J; Williams, Keryn A

2007-01-01

Despite advances in management and treatment, retinopathy of prematurity remains a major cause of childhood blindness. Evidence for a genetic basis for susceptibility to retinopathy of prematurity is examined, including the influences of sex, ethnicity, and ocular pigmentation. The role of polymorphisms is explored in the genes for vascular endothelial growth factor and insulin‐like growth factor‐1, and of mutations in the Norrie disease gene. Insights into the genetic basis of retinopathy of prematurity provided by the animal model of oxygen induced retinopathy are examined. Evidence for a genetic component for susceptibility to retinopathy of prematurity is strong, although the molecular identity of the gene or genes involved remains uncertain. PMID:18024814

Laser treatment for retinopathy of prematurity through the incubator wall.

PubMed

Dogra, Mangat R; Vinekar, Anand; Viswanathan, Kavitha; Sangtam, Tiakumzuk; Das, Pranab; Gupta, Amod; Dutta, Sourab

2008-01-01

In this era of early treatment for retinopathy of prematurity, sick infants who develop aggressive diseases or remain oxygen and temperature dependent may be treated while they are inside the incubator itself, thus avoiding unnecessary delays. This article describes the treatment of eight infants with retinopathy of prematurity who were dependent on an incubator by using a laser indirect ophthalmoscope delivery system through the slanting transparent wall of the incubator. In this series, which is the largest to date, the relative advantages and disadvantages of the procedure are discussed.

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy.

PubMed

Srinivasan, Sangeetha; Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2017-12-01

To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR). Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A1c (HbA1c), nephropathy, neuropathy, and cardiovascular measures were examined. The central zone (P = 0.174), parafoveal thickness (P = 0.090), perifovea (P = 0.592), RNFL (P = 0.866), GCC (P = 0.798), and GCC GLV (P = 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P = 0.036). CNFL was significantly lower in those with mild NPDR (P = 0.004) in comparison to the control group and those with no DR. The CNBD (P = 0.094) and CNFT (P = 0.458) did not differ between the groups. Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

Retinopathy of prematurity and the oxygen conundrum: lessons learned from recent randomized trials.

PubMed

Fleck, Brian W; Stenson, Ben J

2013-06-01

Emerging data from randomised controlled trials of different pulse oximeter oxygen saturation (SpO(2)) target ranges shows that higher SpO(2) targets are associated with a higher risk of severe retinopathy of prematurity. However, the trials have also shown that higher SpO(2) targets are associated with improved survival. In the light of these results and pending the full results for long-term outcome, it is recommended that oxygen saturation targets for preterm infants of gestational age less than 28 weeks at birth should be maintained at or more than 90%. Copyright © 2013 Elsevier Inc. All rights reserved.

Retinopathy of prematurity - from recognition of risk factors to treatment recommendations.

PubMed

Fagerholm, Reija; Vesti, Eija

Retinopathy of prematurity is a proliferative retinal disorder diagnosed exclusively in prematurely born infants. In retinopathy of prematurity, growth of the retinal vasculature is disturbed, leading to hypoxia-induced pathological changes typical of retinopathy of prematurity, in the worst case resulting in retinal detachment. The most typical risk factors predisposing to the disease include hyperoxemia, low levels of insulin-like growth factor 1 (IGF-I), and low birth weight in relation to weeks of pregnancy. Laser therapy of peripheral retina is the currently established form of treatment. Screening is applied in order to recognize the pathological changes in retinopathy of prematurity early enough.

Macular micropseudocysts in early stages of diabetic retinopathy.

PubMed

Tremolada, Gemma; Pierro, Luisa; de Benedetto, Umberto; Margari, Sergio; Gagliardi, Marco; Maestranzi, Gisella; Calori, Giliola; Lorenzi, Mara; Lattanzio, Rosangela

2011-01-01

To identify by noninvasive means early retinal abnormalities that may predict diabetic macular edema. The authors analyzed retrospectively data from consecutive patients with Type 1 (n = 16) or Type 2 (n = 23) diabetes who presented for routine follow-up of early retinopathy, had no clinical signs or symptoms of diabetic macular edema, and were evaluated with spectral-domain optical coherence tomography. Age- and gender-matched nondiabetic subjects provided normative data. Spectral-domain optical coherence tomography revealed in the macular region of diabetic patients small hyporeflective areas (median diameter, 55 μm) contained within discrete retinal layers that we named micropseudocysts (MPCs). Micropseudocysts are associated with vascular leakage. The patients showing MPCs had more frequently systemic hypertension and increased central foveal thickness than those without MPCs. The association with increased central foveal thickness was only in the patients with Type 2 diabetes. Macular MPCs in patients with mild diabetic retinopathy appear to reflect leakage and can precede macular thickening. The association of MPCs with increased central foveal thickness in patients with Type 2 diabetes, but not in patients with Type 1 diabetes, points to a greater tendency to retinal fluid accumulation in patients with Type 2 diabetes. Studies in larger cohorts will determine the usefulness of MPCs in strategies to abort diabetic macular edema.

Verification of multimarkers for detection of early stage diabetic retinopathy using multiple reaction monitoring.

PubMed

Kim, Kyunggon; Kim, Sang Jin; Han, Dohyun; Jin, Jonghwa; Yu, Jiyoung; Park, Kyong Soo; Yu, Hyeong Gon; Kim, Youngsoo

2013-03-01

Diabetic retinopathy (DR) is a complication of diabetes and 80% of diabetes mellitus (DM) patients whose DM duration is over 10 years can be expected to suffer with DR. The diagnosis of DR depends on an ophthalmological examination, and no molecular methods of screening DR status exist. Nonproliferative diabetic retinopathy (NPDR) is the early DR which is hard to be noticed in early NPDR, showing significant cause of adult blindness in type 2 diabetes patients. Protein biomarkers have been valuable in the diagnosis of disease and the use of multiple biomarkers has been suggested to overcome the low specificity of single ones. For biomarker development, multiple reaction monitoring (MRM) has been spotlighted as an alternative method to quantify target proteins with no need for immunoassay. In this study, 54 candidate DR marker proteins from a previous study were verified by MRM in plasma samples from NPDR patients in 3 stages (mild, moderate and severe; 15 cases each) and diabetic patients without retinopathy (15 cases) as a control. Notably, 27 candidate markers distinguished moderate NPDR from type 2 diabetic patients with no diabetic retinopathy, generating AUC values (>0.7). Specifically, 28 candidate proteins underwent changes in expression as type 2 diabetic patients with no diabetic retinopathy progressed to mild and moderate NPDR. Further, a combination of 4 markers from these 28 candidates had the improved specificity in distinguishing moderate NPDR from type 2 diabetic patients with no diabetic retinopathy, yielding a merged AUC value of nearly 1.0. We concluded that MRM is a fast, robust approach of multimarker panel determination and an assay platform that provides improved specificity compared with single biomarker assay systems.

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

PubMed

Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

2017-01-01

Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

Retinopathy of prematurity-induced blindness: birth weight-specific survival and the new epidemic.

PubMed

Gibson, D L; Sheps, S B; Uh, S H; Schechter, M T; McCormick, A Q

1990-09-01

A recent population-based study in the Canadian province of British Columbia showed that, since the mid-1960s, there has been a significant increase in the incidence of retinopathy of prematurity-induced blindness in infants weighing 750 to 999 g at birth. To determine the impact of changing birth weight-specific survival on this new epidemic, all infants born in the province in the period 1952 through 1986 and known to the British Columbia Health Surveillance Registry as having retinopathy of prematurity-induced blindness were identified. In addition, the birth registration records for the 1,299 740 infants born in British Columbia in the same period and the death records of the 22,940 British Columbia-born infants who died in the province before the end of their first year of life were linked using a combination of probabilistic and manual record linkage techniques. These linked records and the records from the Health Surveillance Registry were used to calculate birth weight-specific incidence rates of retinopathy of prematurity-induced blindness in liveborn infants and first-year-of-life survivors. The rates, in 5-year intervals, showed that, in both liveborn infants and first-year survivors, the highest birth weight-specific rates occurred during the first epidemic of retinopathy of prematurity, which ended in British Columbia in 1954. Since the mid-to late-1960s, the incidence of retinopathy of prematurity-induced blindness in liveborn infants weighing less than 1000 g increased steadily whereas in infants weighting 1000 to 1499 g, incidence decreased slightly since the original epidemic ended. However, the experience of first-year-of-life survivors is substantially different.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of subretinal injection on retinal structure and function in a rat oxygen-induced retinopathy model.

PubMed

Becker, Silke; Wang, Haibo; Stoddard, Gregory J; Hartnett, M Elizabeth

2017-01-01

Subretinal injections are used to deliver agents in experimental studies of retinal diseases, often through viral vectors. However, few studies have investigated the effects of subretinal injections alone on the structure and function of the healthy or diseased retina, particularly in models of oxygen-induced retinopathy (OIR). We report on the effects of subretinal injections in a rat OIR model, which is used to study mechanisms of retinopathy of prematurity. Within 6 h of birth, neonatal rat pups were exposed to repeated cycles of oxygen between 50% and 10% O 2 every 24 h for 14 days and subsequently moved to room air. On postnatal day 8 (P8), animals were treated in both eyes with advancement of the injection needle into the vitreous (pilot-treated) or with a subretinal PBS injection (sPBS-treated) or were left untreated (untreated). Additional control animals were exposed to microscope light after eyelid opening only (light-treated). Retinal fundus images were recorded on P26. Areas of the avascular retina and intravitreal neovascularization were determined in flat mounted retinas stained with isolectin B4 on P32. Retinal function of the respective eyes was assessed with the Ganzfeld electroretinogram (ERG) on P31 or P32 and with focal ERG in the central retina on P28 or P29. The thickness of the retinal layers was measured with spectral domain optical coherence tomography (OCT) on P30 and in opsin- and TO-PRO 3-stained retinal cryosections from pups euthanized on P32. Two sections were analyzed in each pup. For each section, three images of three different locations were analyzed accounting for 18 thickness measurements per pup. Compared to untreated animals, the avascular area of the retina was greater in the pilot-treated (p<0.05) and sPBS-treated eyes (p<0.01), and the sPBS-treated eyes had a greater avascular retinal area compared to the pilot-treated eyes (p<0.01). The intravitreal neovascular area was larger in the sPBS-treated eyes compared to the

Predictive algorithms for early detection of retinopathy of prematurity.

PubMed

Piermarocchi, Stefano; Bini, Silvia; Martini, Ferdinando; Berton, Marianna; Lavini, Anna; Gusson, Elena; Marchini, Giorgio; Padovani, Ezio Maria; Macor, Sara; Pignatto, Silvia; Lanzetta, Paolo; Cattarossi, Luigi; Baraldi, Eugenio; Lago, Paola

2017-03-01

To evaluate sensitivity, specificity and the safest cut-offs of three predictive algorithms (WINROP, ROPScore and CHOP ROP) for retinopathy of prematurity (ROP). A retrospective study was conducted in three centres from 2012 to 2014; 445 preterms with gestational age (GA) ≤ 30 weeks and/or birthweight (BW) ≤ 1500 g, and additional unstable cases, were included. No-ROP, mild and type 1 ROP were categorized. The algorithms were analysed for infants with all parameters (GA, BW, weight gain, oxygen therapy, blood transfusion) needed for calculation (399 babies). Retinopathy of prematurity (ROP) was identified in both eyes in 116 patients (26.1%), and 44 (9.9%) had type 1 ROP. Gestational age and BW were significantly lower in ROP group compared with no-ROP subjects (GA: 26.7 ± 2.2 and 30.2 ± 1.9, respectively, p < 0.0001; BW: 839.8 ± 287.0 and 1288.1 ± 321.5 g, respectively, p = 0.0016). Customized alarms of ROPScore and CHOP ROP correctly identified all infants having any ROP or type 1 ROP. WINROP missed 19 cases of ROP, including three type 1 ROP. ROPScore and CHOP ROP provided the best performances with an area under the receiver operating characteristic curve for the detection of severe ROP of 0.93 (95% CI, 0.90-0.96, and 95% CI, 0.89-0.96, respectively), and WINROP obtained 0.83 (95% CI, 0.77-0.87). Median time from alarm to treatment was 11.1, 5.1 and 9.1 weeks, for WINROP, ROPScore and CHOP ROP, respectively. ROPScore and CHOP ROP showed 100% sensitivity to identify sight-threatening ROP. Predictive algorithms are a reliable tool for early identification of infants requiring referral to an ophthalmologist, for reorganizing resources and reducing stressful procedures to preterm babies. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown.

PubMed

Reichhart, Nadine; Crespo-Garcia, Sergio; Haase, Nadine; Golic, Michaela; Skosyrski, Sergej; Rübsam, Anne; Herrspiegel, Christina; Kociok, Norbert; Alenina, Natalia; Bader, Michael; Dechend, Ralf; Strauss, Olaf; Joussen, Antonia M

2017-01-01

Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy. Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats. Systemic treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal function was assessed by Ganzfeld electroretinography (ERG). Retinal vessels in TetO rats showed differences in vessel calibre, together with gliosis. The total number and the proportion of activated mononuclear phagocytes was increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG indicated photoreceptor malfunction. Both the inner and outer blood-retina barriers were affected. The ARB treated group showed reduced gliosis and an overall amelioration of retinal function, alongside RGC recovery, whilst no statistically significant differences in vascular and inflammatory features were detected. The TetO rat represents a promising translational model for the early neurovascular changes associated with type 2 diabetic retinopathy. ARB treatment had an effect on the neuronal component of the retina but not on the vasculature.

Therapeutic effect of the compound Danshen dripping pill combined with laser acupoint irradiation on early diabetic retinopathy

NASA Astrophysics Data System (ADS)

Liu, Hui-Hui; Xiong, Guo-Xin; Zhang, Li-Ping

2017-06-01

To investigate the therapeutic effect of the compound Danshen dripping pill combined with laser acupoint irradiation on early diabetic retinopathy, 19 patients with early diabetic retinopathy were randomly divided into a treatment group and a control group. The TaiYang, YangBai, YuYao and ZanZhu acupoints of patients in the treatment group were irradiated with a semiconductor laser combined with the oral compound Danshen dropping pills, while those in the control group only used the oral compound Danshen dropping pills. The indicators of vision, mean defect of light sensitivity in the visual field, renal function and fasting blood glucose, were examined to evaluate the efficacy. After treatment, the above indicators of patients in the two groups were significantly improved and there was a significant difference between the two groups. This showed that the compound Danshen dripping pills combined with the laser acupoint irradiation can improve the ischemic and anoxic state of early diabetic retinopathy and improve the visual field.

Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

PubMed

Azad, Rajvardhan; Arora, Tarun; Sihota, Ramanjit; Chandra, Parijat; Mahajan, Deepankur; Sain, Siddarth; Sharma, Yograj

2013-10-01

To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

Identification of different macrophage subpopulations with distinct activities in a mouse model of oxygen-induced retinopathy

PubMed Central

Zhu, Yanji; Zhang, Ling; Lu, Qing; Gao, Yushuo; Cai, Yujuan; Sui, Ailing; Su, Ting; Shen, Xi; Xie, Bing

2017-01-01

The aim of the present study was to characterize the phenotypic shift, quantity and role changes in different subgroups of retinal macrophages in a mouse model of oxygen-induced retinopathy (OIR). The mRNA expression levels of macrophage M1 and M2 subgroup marker genes and polarization-associated genes were analyzed by RT-qPCR. The number of M1 and M2 macrophages in our mouse model of OIR was analyzed by flow cytometry at different time points during the progression of OIR. Immunofluorescence whole mount staining of the retinas of mice with OIR was performed at different time points to examine the influx of macrophages, as well as the morphological characteristics and roles of M1 and M2 macrophages. An increased number of macrophages was recruited during the progression of angiogenesis in the retinas of mice with OIR due to the pro-inflammatory microenvironment containing high levels of cell adhesion and leukocyte transendothelial migration molecules. RT-qPCR and flow cytometric analysis at different time points revealed a decline in the number of M1 cells from a significantly high level at post-natal day (P)13 to a relatively normal level at P21, as well as an increase in the number of M2 cells from P13 to P21 in the mice with OIR, implicating a shift of macrophage polarization towards the M2 subtype. Immunofluorescence staining suggested that the M1 cells interacted with endothelial tip cells at the vascular front, while M2 cells embraced the emerging vessels and bridged the neighboring vessel sprouts. Thus, our data indicate that macrophages play an active role in OIR by contributing to the different steps of neovascularization. Our findings indicate that tissue macrophages may be considered as a potential target for the anti-angiogenic therapy of ocular neovascularization disease. PMID:28627621

Fortified extract of red berry, Ginkgo biloba, and white willow bark in experimental early diabetic retinopathy.

PubMed

Bucolo, Claudio; Marrazzo, Giuseppina; Platania, Chiara Bianca Maria; Drago, Filippo; Leggio, Gian Marco; Salomone, Salvatore

2013-01-01

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

Deep Convolutional Neural Network-Based Early Automated Detection of Diabetic Retinopathy Using Fundus Image.

PubMed

Xu, Kele; Feng, Dawei; Mi, Haibo

2017-11-23

The automatic detection of diabetic retinopathy is of vital importance, as it is the main cause of irreversible vision loss in the working-age population in the developed world. The early detection of diabetic retinopathy occurrence can be very helpful for clinical treatment; although several different feature extraction approaches have been proposed, the classification task for retinal images is still tedious even for those trained clinicians. Recently, deep convolutional neural networks have manifested superior performance in image classification compared to previous handcrafted feature-based image classification methods. Thus, in this paper, we explored the use of deep convolutional neural network methodology for the automatic classification of diabetic retinopathy using color fundus image, and obtained an accuracy of 94.5% on our dataset, outperforming the results obtained by using classical approaches.

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants.

PubMed

Jorge, Eliane C; Jorge, Edson N; El Dib, Regina P

2013-08-06

Retinopathy of prematurity (ROP) is a complex condition of the developing retinal blood vessels and is one of the leading causes of preventable childhood blindness. Several risk factors for ROP have been studied over the past 50 years. Among them, general immaturity (low birth weight and low gestational age) and prolonged oxygen therapy have been consistently related to disease onset. However, it is understood that the progression of the disease is multifactorial and may be associated with others risk factors, such as multiple gestation, apnoea, intracranial haemorrhage, anaemia, sepsis, prolonged mechanical ventilation, multiple transfusions and light exposure. Furthermore, the precise role of these individual factors in the development of the disease has not yet been well established. To determine whether the reduction of early environmental light exposure reduces the incidence of retinopathy of prematurity (ROP) or poor ROP outcomes among very low birth weight infants. We searched the following databases: the Cochrane Neonatal Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, HealthSTAR, Science Citation Index Database, CANCERLIT, the Oxford Database of Perinatal Trials and www.clinicaltrials.gov. We also searched previous reviews including cross-references, abstracts, conference and symposia proceedings, and contacted expert informants. This search was updated in October 2012. Randomised or quasi-randomised controlled trials that reduced light exposure to premature infants within the first seven days following birth were considered for this review. We also considered cluster-randomised controlled trials. Data on clinical outcomes including any acute ROP and poor ROP outcome were extracted by both review authors independently and consensus reached. We conducted data analysis according to the standards of the Cochrane Neonatal Review Group. Data from four randomised trials with a total of 897 participants failed to show any

[Diabetic retinopathy: pathogenesis and therapeutic implications].

PubMed

Pelikánová, Terezie

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increase in polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other epigenetic, metabolic and haemodynamic factors, including hypertension, dyslipidemia and oxidative stress. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, proinflammatory cytokines, vasoactive molecules, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant pattern, and finally in angiogenesis and tissue remodelling. Brain, liver, adipose tissue, GUT, skeletal muscle and other tissues could be another source of mediators. Therapeutic approaches used for patients with or at risk for diabetic retinopathy include drug therapy to reduce modifiable risk factors, laser photocoagulation, intravitreous administration of anti-VEGF agents/steroids and intraocular surgery. Screening plays an important role in early detection and intervention to prevent the progression of diabetic retinopathy. Described insights into pathophysiological mechanisms responsible for DR, could help in the development of more targeted approach for prevention and treatment of diabetic retinopathy. anti

Involvement of all-trans-retinal in acute light-induced retinopathy of mice.

PubMed

Maeda, Akiko; Maeda, Tadao; Golczak, Marcin; Chou, Steven; Desai, Amar; Hoppel, Charles L; Matsuyama, Shigemi; Palczewski, Krzysztof

2009-05-29

Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.

Comparison of Dextran Perfusion and GSI-B4 Isolectin Staining in a Mouse Model of Oxygen-induced Retinopathy.

PubMed

Huang, Shaofen; Liang, Jiajian; Yam, Gary Hin-Fai; Lu, Zhihao; Pang, Chi Pui; Chen, Haoyu

2015-06-01

Oxygen-induced retinopathy (OIR) is a robust and widely used animal model for the study of retinal neovascularization (NV). Dextran perfusion and Griffonia simplicifolia isolectin B4 (GSI-B4) staining are two common methods for examining the occurrence and extent of OIR. This study provides a quantitative comparison of the two for OIR detection. At postnatal day 7 (PN7), fifteen C57BL/6J mice were exposed to a 75% hyperoxic condition for 5 days and then returned to room air conditions. At PN17, the mice received intravitreal injection of GSI-B4 Alexa Fluor 568 conjugate. After 10 hours, they were infused with FITC-dextran conjugate via the left ventricle. Retinal flat mounts were photographed by confocal microscopy. Areas with fluorescent signals and the total retinal areas were quantified by Image J software. Both GSI-B4 and dextran detected the peripheral neovascular area. The mean hyper fluorescence area was 0.33 ± 0.14% of whole retinal area determined by GSI-B4 staining and 0.25 ± 0.28% determined by dextran perfusion. The difference between the two measures was 0.08% (95% CI:-0.59%, 0.43%). The Pearson correlation coefficient between the two methods was 0.386,P =0.035. The mean coincidence rates were 14.3 ± 13.4% and 24.9 ± 18.5% for GSI-B4 and dextran staining, respectively. Both methods can complement each other in demonstrating and quantitatively evaluating retinal NV. A poor agreement was found between the two methods; GSI-B4 isolectin was more effective than FITC-dextran perfusion in evaluating the extent of retinal NV in a mouse model of OIR.

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

PubMed

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

2016-05-01

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

Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy

PubMed Central

LeBlanc, Michelle E.; Wang, Weiwen; Chen, Xiuping; Caberoy, Nora B.; Guo, Feiye; Shen, Chen; Ji, Yanli; Tian, Hong; Wang, Hui; Chen, Rui

2017-01-01

Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels. In contrast, VEGF bound to and induced angiogenesis in both diabetic and normal vasculature. Scg3 and VEGF signal through distinct receptor pathways. Importantly, Scg3-neutralizing antibodies alleviated retinal vascular leakage in diabetic mice with high efficacy. Furthermore, anti-Scg3 prevented retinal neovascularization in oxygen-induced retinopathy mice, a surrogate model for retinopathy of prematurity (ROP). ROP is the most common cause of vision impairment in children, with no approved drug therapy. These results suggest that Scg3 is a promising target for novel antiangiogenic therapy of DR and ROP. PMID:28330905

Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

PubMed

Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

2015-01-01

Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

Hypoxia-Induced Retinal Neovascularization in Zebrafish Embryos: A Potential Model of Retinopathy of Prematurity

PubMed Central

Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

2015-01-01

Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2–4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression. PMID:25978439

Blood antioxidant parameters in patients with diabetic retinopathy.

PubMed

Siemianowicz, Krzysztof; Gminski, Jan; Telega, Alicja; Wójcik, Aneta; Posielezna, Barbara; Grabowska-Bochenek, Rozalia; Francuz, Tomasz

2004-09-01

It has been postulated that enhanced generation of reactive oxygen species (ROS) may take part in a pathogenesis of diabetic microvascular complication - retinopathy. There are two types of diabetic retinopathy, non-proliferative (simplex) and proliferative. ROS are anihilated by an intracelluar enzymatic system composed mainly of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Beta-carotene, tocopherols and ascorbic acid are major components of serum antioxidants. All serum antioxidants are usually measured together as total antioxidant status (TAS). Erythrocyte activities of GPx, SOD, CAT and TAS were measured in diabetic patients without retinopathy, with non-proliferative and proliferative retinopathy. Obtained results were correlated with a period of diabetic history and a period of insulin treatment. SOD was significantly elevated in diabetics with non-proliferative retinopathy compared to patients without retinopathy. TAS was significantly lower in patients with proliferative retinopathy than in diabetics not developing retinopathy. Only CAT was significantly negatively correlated with the period of insulin treatment. This significant negative correlation was also observed in a subgroup of patients with proliferative retinopathy.

Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism.

PubMed

Mahmoud, Ayman M; Abd El-Twab, Sanaa M; Abdel-Reheim, Eman S

2017-06-01

Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated. Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks. Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina. These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.

Optical Coherence Tomography Angiography and Ultra-widefield Fluorescein Angiography for Early Detection of Adolescent Sickle Retinopathy.

PubMed

Pahl, Daniel A; Green, Nancy S; Bhatia, Monica; Lee, Margaret T; Chang, Jonathan S; Licursi, Maureen; Briamonte, Courtney; Smilow, Elana; Chen, Royce W S

2017-11-01

Based on standard screening techniques, sickle retinopathy reportedly occurs in 10% of adolescents with sickle cell disease (SCD). We performed a prospective, observational clinical study to determine if ultra-widefield fluorescein angiography (UWFA), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCT-A) detect more-frequent retinopathy in adolescents with SCD. Cross-sectional study. Setting: Institutional. Sixteen adolescents with SCD, aged 10-19 years (mean age 14.9 years), and 5 age-equivalent controls (mean age 17.4 years). Examinations including acuity, standard slit-lamp biomicroscopy, UWFA, SD-OCT, and OCT-A were performed. Sickle retinopathy defined by biomicroscopic changes, Goldberg stages I-V, Penman scale, flow void on OCT-A, or macular thinning on SD-OCT. While 22 of 32 SCD eyes (68.8%) had retinopathy on biomicroscopy, by UWFA 4 of 24 (16.7%) SCD eyes had peripheral arterial occlusion (Goldberg I), and 20 of 24 eyes (83.3%) had peripheral arteriovenous anastomoses (Goldberg II) in addition. No patients had Goldberg stages III-V. By SD-OCT and OCT-A, thinning of the macula and flow voids in both the superficial and deep retinal capillary plexus were found in 6 of 30 (20%) eyes. All 24 eyes with adequate UWFA studies demonstrated sickle retinopathy. SD-OCT and OCT-A, which have not been previously reported in the adolescent population, detected abnormal macular thinning and flow abnormalities undetected by biomicroscopy. These findings suggest that pediatric sickle retinopathy may be more prevalent than previously suspected. If these findings are confirmed with larger cross-sectional and prospective analyses, these approaches may enhance early screening for sickle retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Determining diabetic retinopathy screening interval based on time from no retinopathy to laser therapy.

PubMed

Hughes, Daniel; Nair, Sunil; Harvey, John N

2017-12-01

Objectives To determine the necessary screening interval for retinopathy in diabetic patients with no retinopathy based on time to laser therapy and to assess long-term visual outcome following screening. Methods In a population-based community screening programme in North Wales, 2917 patients were followed until death or for approximately 12 years. At screening, 2493 had no retinopathy; 424 had mostly minor degrees of non-proliferative retinopathy. Data on timing of first laser therapy and visual outcome following screening were obtained from local hospitals and ophthalmology units. Results Survival analysis showed that very few of the no retinopathy at screening group required laser therapy in the early years compared with the non-proliferative retinopathy group ( p < 0.001). After two years, <0.1% of the no retinopathy at screening group required laser therapy, and at three years 0.2% (cumulative), lower rates of treatment than have been suggested by analyses of sight-threatening retinopathy determined photographically. At follow-up (mean 7.8 ± 4.6 years), mild to moderate visual impairment in one or both eyes due to diabetic retinopathy was more common in those with retinopathy at screening (26% vs. 5%, p < 0.001), but blindness due to diabetes occurred in only 1 in 1000. Conclusions Optimum screening intervals should be determined from time to active treatment. Based on requirement for laser therapy, the screening interval for diabetic patients with no retinopathy can be extended to two to three years. Patients who attend for retinal screening and treatment who have no or non-proliferative retinopathy now have a very low risk of eventual blindness from diabetes.

Retinal Oxygen Delivery and Metabolism in Healthy and Sickle Cell Retinopathy Subjects

PubMed Central

Felder, Anthony E.; Tan, Ou; Blair, Norman P.; Huang, David

2018-01-01

Purpose Reduction in inner retinal oxygen delivery (DO2) can cause retinal hypoxia and impair inner retinal oxygen metabolism (MO2), leading to vision loss. The purpose of the current study was to establish measurements of DO2 and MO2 in healthy subjects and test the hypothesis that DO2 and MO2 are reduced in sickle cell retinopathy (SCR) subjects. Methods Dual wavelength retinal oximetry and Doppler optical coherence tomography were performed in 12 healthy control and 12 SCR subjects. Images were analyzed to measure retinal arterial and venous oxygen content (O2A and O2V), venous diameter (DV), and total retinal blood flow (TRBF). Retinal arteriovenous oxygen content difference (O2AV), DO2, MO2, and oxygen extraction fraction (OEF) were calculated according to the following equations: O2AV = O2A − O2V; DO2 = TRBF * O2A; MO2 = TRBF * O2AV; OEF = MO2/DO2. Results Retinal DV and TRBF were higher in the SCR group as compared to the control group, whereas, O2A, O2V, and O2AV were lower in SCR group as compared to the control group. DO2, MO2, and OEF were not significantly different between control and SCR groups. MO2 and DO2 were linearly related, such that higher MO2 was associated with higher DO2. There was an inverse relationship between TRBF and OEF, such that lower TRBF was associated with higher OEF. Conclusions Increased blood flow compensated for decreased oxygen content, thereby maintaining DO2, MO2, and OEF at predominately lower stages of SCR. Quantitative assessment of these parameters has the potential to advance knowledge and improve diagnostic evaluation of retinal ischemic conditions. PMID:29677351

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy.

PubMed

Simmons, Aaron B; Bretz, Colin A; Wang, Haibo; Kunz, Eric; Hajj, Kassem; Kennedy, Carson; Yang, Zhihong; Suwanmanee, Thipparat; Kafri, Tal; Hartnett, M Elizabeth

2018-05-05

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

PTB-associated splicing factor inhibits IGF-1-induced VEGF upregulation in a mouse model of oxygen-induced retinopathy.

PubMed

Dong, Lijie; Nian, Hong; Shao, Yan; Zhang, Yan; Li, Qiutang; Yi, Yue; Tian, Fang; Li, Wenbo; Zhang, Hong; Zhang, Xiaomin; Wang, Fei; Li, Xiaorong

2015-05-01

Pathological retinal neovascularization, including retinopathy of prematurity and age-related macular degeneration, is the most common cause of blindness worldwide. Insulin-like growth factor-1 (IGF-1) has a direct mitogenic effect on endothelial cells, which is the basis of angiogenesis. Vascular endothelial growth factor (VEGF) activation in response to IGF-1 is well documented; however, the molecular mechanisms responsible for the termination of IGF-1 signaling are still not completely elucidated. Here, we show that the polypyrimidine tract-binding protein-associated splicing factor (PSF) is a potential negative regulator of VEGF expression induced by IGF stimulation. Functional analysis demonstrated that ectopic expression of PSF inhibits IGF-1-stimulated transcriptional activation and mRNA expression of the VEGF gene, whereas knockdown of PSF increased IGF-1-stimulated responses. PSF recruited Hakai to the VEGF transcription complex, resulting in inhibition of IGF-1-mediated transcription. Transfection with Hakai siRNA reversed the PSF-mediated transcriptional repression of VEGF gene transcription. In summary, these results show that PSF can repress the transcriptional activation of VEGF stimulated by IGF-1 via recruitment of the Hakai complex and delineate a novel regulatory mechanism of IGF-1/VEGF signaling that may have implications in the pathogenesis of neovascularization in ocular diseases.

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

PubMed Central

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

2011-01-01

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

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

Features of retinopathy of prematurity in a tertiary care hospital in Lahore.

PubMed

Jamil, Ahmad Zeeshan; Tahir, Muhammad Younis; Ayub, Muhammad Hammad; Mirza, Khurram Azam

2015-02-01

To study the demographic and clinical features of Retinopathy of Prematurity in urban Punjab. The cross-sectional study was performed at Hameed Latif Hospital, Lahore, from April 2010 to October 2013 and comprised neonates born with birth weight less than 2000 g, gestational age less than 37 weeks, or those who were considered high risk for Retinopathy of Prematurity. Variables recorded included history, birth weight, gestational age, oxygen supplementation, development of Retinopathy of Prematurity, and laser treatment. Data was analysed using SPSS 17. There were 285 neonates in the study with a mean birth weight of 1280.34 ± 350.43 g and mean gestational age being 29.38 ± 3.14 weeks. Overall, 167 (58.6%) received supplemental oxygen, 86(30.2%) were anaemic and 44 (15.4%) received blood transfusion. Besides, 47 (16.5%) premature babies were product of multiple gestation, 34 (11.9%) were having respiratory distress, 25 (8.8%) had sepsis and received intravenous antibiotics, 70(24.6%) developed Retinopathy of Prematurity, and 22 (7.7%) developed threshold disease and received laser treatment at mean gestational age of 32.11 ± 2.53 weeks. Screening is key to preventing childhood blindness caused by Retinopathy of Prematurity. Prematurity, low birth weight and supplemental oxygen therapy are significant risk factors for the condition.

Educational paper: Retinopathy of prematurity.

PubMed

Casteels, Ingele; Cassiman, Catherine; Van Calster, Joachim; Allegaert, Karel

2012-06-01

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness. Over the past two decades, major advances have been made in understanding the pathogenesis of ROP, to a large extent as a result of changes in clinical risk factors (oxygen and non-oxygen related) and characteristics observed in ROP cases. This article provides a literature review on the evolution in clinical characteristics, classification and treatment modalities and indications of ROP. Special attention is hereby paid to the neonatal factors influencing the development of ROP and to the necessity for everyone caring for premature babies to have a well-defined screening and treatment protocol for ROP. Such screening protocol needs to be based on a unit-specific ROP risk profile and, consequently, may vary between different European regions. Retinopathy of prematurity is an important cause of ocular morbidity and blindness in children. With better understanding of the pathogenesis, screening and treatment guidelines have changed over time and are unit specific.

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

PubMed Central

Rajagopal, Rithwick; Bligard, Gregory W.; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter

2016-01-01

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

Biomarkers in Diabetic Retinopathy

PubMed Central

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

Early postnatal weight gain as a predictor for the development of retinopathy of prematurity.

PubMed

Biniwale, Manoj; Weiner, Angela; Sardesai, Smeeta; Cayabyab, Rowena; Barton, Lorayne; Ramanathan, Rangasamy

2017-10-01

The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.

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

Detection of Hypertension Retinopathy Using Deep Learning and Boltzmann Machines

NASA Astrophysics Data System (ADS)

Triwijoyo, B. K.; Pradipto, Y. D.

2017-01-01

hypertensive retinopathy (HR) in the retina of the eye is disturbance caused by high blood pressure disease, where there is a systemic change of arterial in the blood vessels of the retina. Most heart attacks occur in patients caused by high blood pressure symptoms of undiagnosed. Hypertensive retinopathy Symptoms such as arteriolar narrowing, retinal haemorrhage and cotton wool spots. Based on this reasons, the early diagnosis of the symptoms of hypertensive retinopathy is very urgent to aim the prevention and treatment more accurate. This research aims to develop a system for early detection of hypertension retinopathy stage. The proposed method is to determine the combined features artery and vein diameter ratio (AVR) as well as changes position with Optic Disk (OD) in retinal images to review the classification of hypertensive retinopathy using Deep Neural Networks (DNN) and Boltzmann Machines approach. We choose this approach of because based on previous research DNN models were more accurate in the image pattern recognition, whereas Boltzmann machines selected because It requires speedy iteration in the process of learning neural network. The expected results from this research are designed a prototype system early detection of hypertensive retinopathy stage and analysed the effectiveness and accuracy of the proposed methods.

Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

PubMed

Lee, S C; Lee, E T; Kingsley, R M; Wang, Y; Russell, D; Klein, R; Warn, A

2001-04-01

To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

PubMed

Xiao, Zhitao; Zhang, Xinpeng; Geng, Lei; Zhang, Fang; Wu, Jun; Tong, Jun; Ogunbona, Philip O; Shan, Chunyan

2017-10-26

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF.

PubMed

Ridano, Magali E; Subirada, Paula V; Paz, María C; Lorenc, Valeria E; Stupirski, Juan C; Gramajo, Ana L; Luna, José D; Croci, Diego O; Rabinovich, Gabriel A; Sánchez, María C

2017-05-16

Neovascular retinopathies are leading causes of irreversible blindness. Although vascular endothelial growth factor (VEGF) inhibitors have been established as the mainstay of current treatment, clinical management of these diseases is still limited. As retinal impairment involves abnormal neovascularization and neuronal degeneration, we evaluated here the involvement of galectin-1 in vascular and non-vascular alterations associated with retinopathies, using the oxygen-induced retinopathy (OIR) model. Postnatal day 17 OIR mouse retinas showed the highest neovascular profile and exhibited neuro-glial injury as well as retinal functional loss, which persisted until P26 OIR. Concomitant to VEGF up-regulation, galectin-1 was highly expressed in P17 OIR retinas and it was mainly localized in neovascular tufts. In addition, OIR induced remodelling of cell surface glycophenotype leading to exposure of galectin-1-specific glycan epitopes. Whereas VEGF returned to baseline levels at P26, increased galectin-1 expression persisted until this time period. Remarkably, although anti-VEGF treatment in P17 OIR improved retinal vascularization, neither galectin-1 expression nor non-vascular and functional alterations were attenuated. However, this functional defect was partially prevented in galectin-1-deficient (Lgals1-/-) OIR mice, suggesting the importance of targeting both VEGF and galectin-1 as non-redundant independent pathways. Supporting the clinical relevance of these findings, we found increased levels of galectin-1 in aqueous humor from patients with proliferative diabetic retinopathy and neovascular glaucoma. Thus, using an OIR model and human samples, we identified a role for galectin-1 accompanying vascular and non-vascular retinal alterations in neovascular retinopathies.

Cytometric analysis of retinopathies in retinal trypsin digests

NASA Astrophysics Data System (ADS)

Ghanian, Zahra; Staniszewski, Kevin; Sorenson, Christine M.; Sheibani, Nader; Ranji, Mahsa

2014-03-01

The objective of this work was to design an automated image cytometry tool for determination of various retinal vascular parameters including extraction of features that are relevant to postnatal retinal vascular development, and the progression of diabetic retinopathy. To confirm the utility and accuracy of the software, retinal trypsin digest from TSP1-/- and diabetic Akita/+; TSP1-/- mice were analyzed. TSP1 is a critical inhibitor of development of retinopathies and lack of TSP1 exacerbates progression of early diabetic retinopathies. Loss of vascular cells of and gain more acellular capillaries as two major signs of diabetic retinopathies were used to classify a retina as normal or injured. This software allows quantification and high throughput assessment of retinopathy changes associated with diabetes.

Aggressive posterior retinopathy of prematurity in two of the triplets: a case report.

PubMed

Wang, Dan; Zhang, Bo; Dong, Yu; Song, E

2015-02-01

Aggressive posterior retinopathy of prematurity is identified as a rare, rapidly progressing and severe form of retinopathy of prematurity (ROP). Here, we report the diagnosis and treatment of aggressive posterior retinopathy of prematurity (APROP) in two of the triplets born at low birth weight and small gestational age. A case concerning two triplets who were born at 31 weeks' gestational age with low birth weight and reached bilateral threshold APROP was reported. The ROP of triplets A and B had the characteristic features of aggressive diseases, which were posterior location, prominence of plus disease and rapid progression. Low birth weight and small gestational age, multiple pregnancies, pregnancy-induced hypertension and older age of the mother might account for the presentations of APROP. These cases demonstrate the importance of early screening and diagnosis in APROP infants. Prompt and adequate laser photocoagulation with a large number of high-intensity closely performed spots and early retreatment could be effective and safe for preventing the progression of APROP with plus disease in zone 1 or 2 in premature triplets. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

NADPH Oxidase versus Mitochondria-Derived ROS in Glucose-Induced Apoptosis of Pericytes in Early Diabetic Retinopathy

PubMed Central

Mustapha, Nik M.; Tarr, Joanna M.; Kohner, Eva M.; Chibber, Rakesh

2010-01-01

Objectives. Using apocynin (inhibitor of NADPH oxidase), and Mitoquinol 10 nitrate (MitoQ; mitochondrial-targeted antioxidant), we addressed the importance of mitochondria versus NADPH oxidase-derived ROS in glucose-induced apoptosis of pericytes. Methods. NADPH oxidase was localised using Western blot analysis and cytochrome C reduction assay. Apoptosis was detected by measuring caspase-3 activity. Intracellular glucose concentration, ROS formation and Nε-(carboxymethyl) lysine (CML) content were measured using Amplex Red assay kit, dihydroethidium (DHE), and competitive immunoabsorbant enzyme-linked assay (ELISA), respectively. Results. NADPH oxidase was localised in the cytoplasm of pericytes suggesting ROS production within intracellular compartments. High glucose (25 mM) significantly increased apoptosis, intracellular glucose concentration, and CML content. Apoptosis was associated with increased gp91phox expression, activity of NADPH oxidase, and intracellular ROS production. Apocynin and not MitoQ significantly blunted the generation of ROS, formation of intracellular CML and apoptosis. Conclusions. NADPH oxidase and not mitochondria-derived ROS is responsible for the accelerated apoptosis of pericytes in diabetic retinopathy. PMID:20652059

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

PubMed

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

2016-04-01

Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Retinopathy of Prematurity.

ERIC Educational Resources Information Center

Trief, E.; And Others

1989-01-01

Retinopathy of prematurity (ROP) has increased due to a high incidence of premature, low birthweight infants. Stages of severity range from no visual damage to total blindness, and educational problems of ROP children parallel those of other visually impaired children, early intervention being crucial. Treatments are either pharmacological or…

Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility

PubMed Central

Yu, Chunhong; Yi, Jinglin; Yin, Xiaolong; Deng, Yan; Liao, Yujun; Li, Xiaobing

2015-01-01

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP. PMID:26823875

The effect of baicalin in a mouse model of retinopathy of prematurity

PubMed Central

Jo, Hyoung; Jung, Sang Hoon; Yim, Hye Bin; Lee, Sung Jin; Kang, Kui Dong

2015-01-01

Baicalin is a flavonoid derived from the dried root of Scutellaria baicalensis. In this study, oxygen-induced retinopathy was used to characterize the anti-angiogenic properties of baicalin in mice. Pups were exposed to a hyperbaric oxygen environment to induce retinal angiogenesis and were subjected to intraperitoneal injection of baicalin. Avascular area, neovascular tufts, and neovascular lumens were quantified from digital images. Compared to the vehicle, baicalin clearly reduced the central avascular zone and the number of neovascular tufts and lumens. High-dose baicalin (10 mg/kg) significantly reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, angiotensin II, and vascular endothelial growth factor (VEGF). These results show that baicalin is a powerful antiangiogenic compound that attenuates new vessel formation in the retina after systemic administration, and is a candidate substance for therapeutic inhibition of retinal angiogenesis. [BMB Reports 2015; 48(5): 271-276] PMID:25154719

Oxygen and Early Animal Evolution

NASA Astrophysics Data System (ADS)

Xiao, S.

2012-12-01

It is often hypothesized that the rise of animals was triggered by an increase in O2 levels in the atmosphere and oceans. However, this hypothesis is remarkably difficult to test, because the timing of animal divergences is poorly resolved, the physiology of early animals is often unknown, estimates of past pO2 levels come with large error bars, and causal relationships between oxygenation and animal evolution are difficult to establish. Nonetheless, existing phylogenetic, paleontological, and geochemical data indicate that the evolution of macroscopic animals and motile macrometazoans with energetically expensive lifestyles may be temporally coupled with ocean oxygenation events in the Ediacaran Period. Thus, it is plausible that ocean oxygenation may have been a limiting factor in the early evolution of macroscopic, complex, and metabolically aggressive animals (particularly bilaterian animals). However, ocean oxygenation and animal evolution were likely engaged in two-way interactions: Ediacaran oxygenation may have initially lifted a physiological barrier for the evolution of animal size, motility, and active lifestyles, but subsequent animal diversification in the Paleozoic may have also changed oceanic redox structures. Viewed in a broader context, the early evolutionary history of animals was contingent upon a series of events, including genetic preparation (developmental genetics), environmental facilitation (oceanic oxygenation), and ecological escalation (Cambrian explosion), but the rise of animals to ecological importance also had important geobiological impacts on oceanic redox structures, sedimentary fabrics, and global geochemical cycles.

OCT angiography and visible-light OCT in diabetic retinopathy.

PubMed

Nesper, Peter L; Soetikno, Brian T; Zhang, Hao F; Fawzi, Amani A

2017-10-01

In recent years, advances in optical coherence tomography (OCT) techniques have increased our understanding of diabetic retinopathy, an important microvascular complication of diabetes. OCT angiography is a non-invasive method that visualizes the retinal vasculature by detecting motion contrast from flowing blood. Visible-light OCT shows promise as a novel technique for quantifying retinal hypoxia by measuring the retinal oxygen delivery and metabolic rates. In this article, we discuss recent insights provided by these techniques into the vascular pathophysiology of diabetic retinopathy. The next milestones for these modalities are large multicenter studies to establish consensus on the most reliable and consistent outcome parameters to study diabetic retinopathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optical Coherence Tomography Angiography Features of Diabetic Retinopathy

PubMed Central

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

2015-01-01

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

Preclinical screening for retinopathy of prematurity risk using IGF1 levels at 3 weeks post-partum.

PubMed

Pérez-Muñuzuri, Alejandro; Couce-Pico, Maria Luz; Baña-Souto, Ana; López-Suárez, Olalla; Iglesias-Deus, Alicia; Blanco-Teijeiro, José; Fernández-Lorenzo, José Ramón; Fraga-Bermúdez, José María

2014-01-01

Following current recommendations for preventing retinopathy of prematurity (ROP) involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

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.

Ultra-wide-field imaging in diabetic retinopathy.

PubMed

Ghasemi Falavarjani, Khalil; Tsui, Irena; Sadda, Srinivas R

2017-10-01

Since 1991, 7-field images captured with 30-50 degree cameras in the Early Treatment Diabetic Retinopathy Study were the gold standard for fundus imaging to study diabetic retinopathy. Ultra-wide-field images cover significantly more area (up to 82%) of the fundus and with ocular steering can in many cases image 100% of the fundus ("panretinal"). Recent advances in image analysis of ultra-wide-field imaging allow for precise measurements of the peripheral retinal lesions. There is a growing consensus in the literature that ultra-wide-field imaging improves detection of peripheral lesions in diabetic retinopathy and leads to more accurate classification of the disease. There is discordance among studies, however, on the correlation between peripheral diabetic lesions and diabetic macular edema and optimal management strategies to treat diabetic retinopathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Digital tool for detecting diabetic retinopathy in retinography image using gabor transform

NASA Astrophysics Data System (ADS)

Morales, Y.; Nuñez, R.; Suarez, J.; Torres, C.

2017-01-01

Diabetic retinopathy is a chronic disease and is the leading cause of blindness in the population. The fundamental problem is that diabetic retinopathy is usually asymptomatic in its early stage and, in advanced stages, it becomes incurable, hence the importance of early detection. To detect diabetic retinopathy, the ophthalmologist examines the fundus by ophthalmoscopy, after sends the patient to get a Retinography. Sometimes, these retinography are not of good quality. This paper show the implementation of a digital tool that facilitates to ophthalmologist provide better patient diagnosis suffering from diabetic retinopathy, informing them that type of retinopathy has and to what degree of severity is find . This tool develops an algorithm in Matlab based on Gabor transform and in the application of digital filters to provide better and higher quality of retinography. The performance of algorithm has been compared with conventional methods obtaining resulting filtered images with better contrast and higher.

Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project.

PubMed

Santos, Ana Rita; Ribeiro, Luísa; Bandello, Francesco; Lattanzio, Rosangela; Egan, Catherine; Frydkjaer-Olsen, Ulrik; García-Arumí, José; Gibson, Jonathan; Grauslund, Jakob; Harding, Simon P; Lang, Gabriele E; Massin, Pascale; Midena, Edoardo; Scanlon, Peter; Aldington, Stephen J; Simão, Sílvia; Schwartz, Christian; Ponsati, Berta; Porta, Massimo; Costa, Miguel Ângelo; Hernández, Cristina; Cunha-Vaz, José; Simó, Rafael

2017-09-01

This cross-sectional study evaluated the relationship between 1 ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2 ) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes. © 2017 by the American Diabetes Association.

Retinopathy of prematurity: a new epidemic?

PubMed

Gibson, D L; Sheps, S B; Schechter, M T; Wiggins, S; McCormick, A Q

1989-04-01

This study provides the first empiric evidence for the existence of a new epidemic of retinopathy of prematurity-induced blindness. Data from a population-based register of handicapping conditions in the Canadian province of British Columbia, and a birth weight-specific census of live-born infants in British Columbia, were used to determine annual, population-level incidences of retinopathy of prematurity-induced blindness during 1952 to 1983. Changes in incidence since the end of the original epidemic (1954) were determined by subdividing the 29-year period (1955 to 1983) into two intervals (1955 to 1964 and 1965 to 1983). Standardized incidence ratio analyses revealed a marginally significant increase in the overall incidence of retinopathy of prematurity-induced blindness in the later as compared with the earlier period. Infants weighing 750 to 999 g at birth had a significantly increased standardized incidence ratio of 3.07 (95% confidence interval 1.26, 11.06). No increases in risk were observed in heavier or lighter weight infants. Because ascertainment and diagnostic changes do not explain the weight-specific increases in incidence, these results provide the first population-level evidence for a new epidemic.

PHARMACOLOGIC INTERVENTIONS FOR THE PREVENTION AND TREATMENT OF RETINOPATHY OF PREMATURITY

PubMed Central

Beharry, Kay D.; Valencia, G.B.; Lazzaro, D.R.; Aranda, J.V.

2016-01-01

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are key in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, anti-oxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms and synergistic approaches should be considered to maximize efficacy and safety. PMID:26831641

Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial.

PubMed

Sjølie, Anne Katrin; Klein, Ronald; Porta, Massimo; Orchard, Trevor; Fuller, John; Parving, Hans Henrik; Bilous, Rudy; Chaturvedi, Nish

2008-10-18

Diabetic retinopathy remains a leading cause of visual loss in people of working age. We examined whether candesartan treatment could slow the progression and, secondly, induce regression of retinopathy in people with type 2 diabetes. We did a randomised, double-blind, parallel-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00252694. 1905 participants (aged 37-75 years) were randomised to candesartan (n=951) or placebo (n=954). 161 (17%) patients in the candesartan group and 182 (19%) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale. The risk of progression of retinopathy was non-significantly reduced by 13% in patients on candesartan compared with those on placebo (hazard ratio [HR] 0.87, 95% CI 0.70-1.08, p=0.20). Regression on active treatment was increased by 34% (1.34, 1.08-1.68, p=0.009). HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30, p=0.003). Adverse events did not differ between the treatment groups. Treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy.

Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models

PubMed Central

Chen, Ying; Hu, Yang; Lin, Mingkai; Jenkins, Alicia J.; Keech, Anthony C.; Mott, Robert; Lyons, Timothy J.; Ma, Jian-xing

2013-01-01

Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARα dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARα agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-κB in the retinas of OIR and diabetic models. Fenofibrate’s beneficial effects were blocked by a specific PPARα antagonist. Furthermore, Pparα knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARα-dependent mechanism. PMID:23043158

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. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Resolvin D1 inhibits inflammatory response in STZ-induced diabetic retinopathy rats: Possible involvement of NLRP3 inflammasome and NF-κB signaling pathway.

PubMed

Yin, Yizhou; Chen, Fei; Wang, Wenyan; Wang, Han; Zhang, Xuedong

2017-01-01

To investigate the effect of resolvin D1 (RvD1) on the Nod-like receptor family pyrin domain-containing (NLRP3) inflammasome and the nuclear factor-kappa beta (NF-κB) pathway in streptozotocin (STZ)-induced diabetic retinopathy in rats. Ninety-six male rats were divided into four groups: control, STZ, RvD1, and vehicle. The rats with diabetic retinopathy induced by STZ in the RvD1 and vehicle groups were given an intravitreal injection of RvD1 (1,000 ng/kg) or the same dosage of vehicle, respectively. All rats were euthanized 7 days following treatment. Hematoxylin and eosin staining was used to observe the pathological changes in the retinal tissues. The location and expression of the NLRP3 inflammasome components, including NLRP3, caspase-associated recruitment domain (ASC), and caspase-1, in the retinas were detected using immunohistochemistry, real-time PCR, and western blot, respectively. Retinal homogenate of rats were collected for the detection of the downstream molecules interleukin 1 beta (IL-1β) and IL-18 of the NLRP3 inflammasome with enzyme-linked immunosorbent assay kits. The levels of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 were upregulated in the retinas of the STZ-induced diabetic rats; however, these changes were partially inhibited by the RvD1 treatment. Furthermore, the administration of RvD1 suppressed activation of NF-kB, which was upregulated in STZ-induced diabetic retinopathy. RvD1 plays a protective role in STZ-induced diabetic retinopathy by inhibiting the level of activation of the NLRP3 inflammasome and associated cytokine production, suggesting targeting of this pathway might be an effective strategy in treatment of diabetic retinopathy.

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats.

PubMed

Li, Lin; Li, Yan-Lin; Zhou, Yun-Feng; Ge, Zheng-Yan; Wang, Li-Li; Li, Zhi-Qiang; Guo, Yu-Jie; Jin, Long; Ren, Ye; Liu, Jian-Xun; Xu, Yang

2017-06-01

To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA). High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (P<0.01, P<0.05). JXR significantly increased insulin level (P<0.05), and decreased glucagon level (P<0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment. JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.

Role of Inflammation in Diabetic Retinopathy

PubMed Central

Rübsam, Anne; Parikh, Sonia; Fort, Patrice E.

2018-01-01

Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy was considered only a microvascular complication, but the retinal microvasculature is intimately associated with and governed by neurons and glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made to improve the vascular alterations, there is still no treatment to counteract the early neuro-glial perturbations in diabetic retinopathy. Diabetes is a complex metabolic disorder, characterized by chronic hyperglycemia along with dyslipidemia, hypoinsulinemia and hypertension. Increasing evidence points to inflammation as one key player in diabetes-associated retinal perturbations, however, the exact underlying molecular mechanisms are not yet fully understood. Interlinked molecular pathways, such as oxidative stress, formation of advanced glycation end-products and increased expression of vascular endothelial growth factor have received a lot of attention as they all contribute to the inflammatory response. In the current review, we focus on the involvement of inflammation in the pathophysiology of diabetic retinopathy with special emphasis on the functional relationships between glial cells and neurons. Finally, we summarize recent advances using novel targets to inhibit inflammation in diabetic retinopathy. PMID:29565290

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

PubMed

Somfai, Gábor Márk; Tátrai, Erika; Laurik, Lenke; Varga, Boglárka; Ölvedy, Veronika; Jiang, Hong; Wang, Jianhua; Smiddy, William E; Somogyi, Anikó; DeBuc, Delia Cabrera

2014-04-12

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

VEGF as a Survival Factor in Ex Vivo Models of Early Diabetic Retinopathy.

PubMed

Amato, Rosario; Biagioni, Martina; Cammalleri, Maurizio; Dal Monte, Massimo; Casini, Giovanni

2016-06-01

Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR. Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants. Data were obtained with real-time RT-PCR, Western blot, ELISA, and immunohistochemistry. Apoptosis was induced in the retinal explants by HG, OS, or AGE treatments. At the same time, explants also showed increased VEGF expression and release. The data revealed that VEGF is released shortly after exposure of the explants to stressors and before the level of cell death reaches its maximum. Retinal cell apoptosis was inhibited by OCT and PACAP. At the same time, OCT and PACAP also reduced VEGF expression and release. Vascular endothelial growth factor turned out to be a protective factor for the stressed retinal explants, because inhibiting VEGF with a VEGF trap further increased cell death. These data show that protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. These observations suggest that the retina in early DR releases VEGF as a prosurvival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.

Retinal O-linked N-acetylglucosamine protein modifications: implications for postnatal retinal vascularization and the pathogenesis of diabetic retinopathy

PubMed Central

Sieg, Kelsey M.; Shallow, Keegan D.; Sorenson, Christine M.; Sheibani, Nader

2013-01-01

Purpose Hyperglycemia activates several metabolic pathways, including the hexosamine biosynthetic pathway. Uridine diphosphate N-acetylglucosamine (GlcNAc) is the product of the hexosamine biosynthetic pathway and the substrate for O-linked GlcNAc (O-GlcNAc) modification. This modification affects a wide range of proteins by altering their activity, cellular localization, and/or protein interactions. However, the role O-GlcNAcylation may play in normal postnatal retinal vascular development and in the ocular complications of diabetes, including diabetic retinopathy, requires further investigation. Methods The total levels of O-GlcNAc-modified proteins were evaluated by western blot analysis of lysates prepared from retinas obtained at different days during postnatal retinal vascularization and oxygen-induced ischemic retinopathy. Similar experiments were performed with retinal lysate prepared from diabetic Ins2Akita/+ mice with different durations of diabetes and retinal vascular cells cultured under various glucose conditions. The localization of O-GlcNAc-modified proteins in the retinal vasculature was confirmed by immunofluorescence staining. The impact of altered O-GlcNAcylation on the migration of retinal vascular cells was determined using scratch wound and transwell migration assays. Results We detected an increase in protein O-GlcNAcylation during mouse postnatal retinal vascularization and aging, in part through the regulation of the enzymes that control this modification. The study of the diabetic Ins2Akita/+ mouse retina showed an increase in the O-GlcNAc modification of retinal proteins. We also observed an increase in retinal O-GlcNAcylated protein levels during the neovascularization phase of oxygen-induced ischemic retinopathy. Our fluorescence microscopy data confirmed that the alterations in retinal O-GlcNAcylation are similarly represented in the retinal vasculature and in retinal pericytes and endothelial cells. Particularly, the migration of

CD40 in Retinal Müller Cells Induces P2X7-Dependent Cytokine Expression in Macrophages/Microglia in Diabetic Mice and Development of Early Experimental Diabetic Retinopathy.

PubMed

Portillo, Jose-Andres C; Lopez Corcino, Yalitza; Miao, Yanling; Tang, Jie; Sheibani, Nader; Kern, Timothy S; Dubyak, George R; Subauste, Carlos S

2017-02-01

Müller cells and macrophages/microglia are likely important for the development of diabetic retinopathy; however, the interplay between these cells in this disease is not well understood. An inflammatory process is linked to the onset of experimental diabetic retinopathy. CD40 deficiency impairs this process and prevents diabetic retinopathy. Using mice with CD40 expression restricted to Müller cells, we identified a mechanism by which Müller cells trigger proinflammatory cytokine expression in myeloid cells. During diabetes, mice with CD40 expressed in Müller cells upregulated retinal tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), intracellular adhesion molecule 1 (ICAM-1), and nitric oxide synthase (NOS2), developed leukostasis and capillary degeneration. However, CD40 did not cause TNF-α or IL-1β secretion in Müller cells. TNF-α was not detected in Müller cells from diabetic mice with CD40 + Müller cells. Rather, TNF-α was upregulated in macrophages/microglia. CD40 ligation in Müller cells triggered phospholipase C-dependent ATP release that caused P2X 7 -dependent production of TNF-α and IL-1β by macrophages. P2X 7 -/- mice and mice treated with a P2X 7 inhibitor were protected from diabetes-induced TNF-α, IL-1β, ICAM-1, and NOS2 upregulation. Our studies indicate that CD40 in Müller cells is sufficient to upregulate retinal inflammatory markers and appears to promote experimental diabetic retinopathy and that Müller cells orchestrate inflammatory responses in myeloid cells through a CD40-ATP-P2X 7 pathway. © 2017 by the American Diabetes Association.

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

PubMed Central

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

2016-01-01

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

Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

PubMed

Vujosevic, Stela; Bottega, Elisa; Casciano, Margherita; Pilotto, Elisabetta; Convento, Enrica; Midena, Edoardo

2010-06-01

The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. Micropulse diode laser seems to be as

Global DNA methylation as a possible biomarker for diabetic retinopathy.

PubMed

Maghbooli, Zhila; Hossein-nezhad, Arash; Larijani, Bagher; Amini, Manochehr; Keshtkar, Abbasali

2015-02-01

We evaluated whether global levels of DNA methylation status were associated with retinopathy as well as providing a predictive role of DNA methylation in developing retinopathy in a case-control study of 168 patients with type 2 diabetes. The 5-methylcytosine content was assessed by reversed-phase high-pressure liquid chromatography of peripheral blood leukocytes to determine an individual's global DNA methylation status in the two groups, either with or without retinopathy. The global DNA methylation levels were significantly higher in diabetic retinopathy patients compared with those in non-retinopathy patients (4.90 ± 0.12 vs. 4.22 ± 0.13, respectively; p = 0.001). There was a significant increasing trend in global DNA methylation levels in terms of progressing retinopathy (without retinopathy, 4.22 ± 0.13; non-proliferative diabetic retinopathy, 4.62 ± 0.17; proliferative diabetic retinopathy, 5.07 ± 0.21) (p = 0.006). Additionally, global DNA methylation independent of retinopathy risk factors, which include dyslipidaemia, hypertension, hyperglycaemia and duration of diabetes, was a predictive factor for retinopathy (OR = 1.53, p = 0.015). Global DNA methylation is modulated during or possibly before the primary stage of diabetes. This observation verifies the metabolic memory effect of hyperglycaemia in early stage of an aetiological process that leads to type 2 diabetes and its associated complications. Copyright © 2014 John Wiley & Sons, Ltd.

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

Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity.

PubMed

Beharry, Kay D; Valencia, Gloria B; Lazzaro, Douglas R; Aranda, Jacob V

2016-04-01

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are the keys in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, antioxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms, and synergistic approaches should be considered to maximize efficacy and safety. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Correlation between Cystatin C and retinopathy of type-two diabetes mellitus patients.

PubMed

Qian, C; Wan, G M; Yan, P S; Wang, W Z; Liang, S Z; Dong, Y

2017-01-01

Diabetic retinopathy is one of most common diabetic microvascular complications. In recent years the incidence of the disease has increased, hence early diagnosis and treatment are of great importance. In order to find reliable biological indexes to diagnose and treat type-two diabetes mellitus promptly, this study focused on the correlation between Cystatin C (Cys C) and retinopathy of type-two diabetes mellitus patients. One hundred and eighty type-two diabetes mellitus patients and one hundred healthy controls (the control group) were chosen in this study. Of the patients ninety-eight patients had typetwo diabetes mellitus without retinopathy (non-diabetic retinopathy group) and eighty-two had typetwo diabetes mellitus with retinopathy (diabetic retinopathy group). Correlation of Cys C and typetwo diabetic retinopathy was analyzed by examining the waist-hip ratio, fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (HbA1c), and Cys C of both groups. The results showed that FBG, TC, TG, LDL-C, HbA1c, Cys C in the type-two diabetes mellitus patients group were higher than those of the control group (P less than 0.05). Age, course of diabetes, FBG, HbA1c, and Cys C levels were statistically significant in both the DR group and NDR group (P less than 0.05). The result of logistic regression analysis indicates that there was a positive correlation between type-two diabetic retinopathy development and age, course of diabetes, and Cys C level (P less than 0.05). Thus, it can be seen that changes of Cys C levels can assist early diagnosis and treatment of diabetic retinopathy to some extent. The patients with high Cys C level, long course of diabetes, and old age are more likely to have diabetic retinopathy.

Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

PubMed

Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

2009-12-01

A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.

PubMed

Wang, Wenjun; Wang, Qing; Wan, Danyang; Sun, Yue; Wang, Lin; Chen, Hong; Liu, Chengyu; Petersen, Robert B; Li, Jianshuang; Xue, Weili; Zheng, Ling; Huang, Kun

2017-05-04

Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.

Presumed topiramate retinopathy: a case report.

PubMed

Yeung, Tiffany L M; Li, Patrick S H; Li, Kenneth K W

2016-08-01

We report a case of peripheral pigmentary retinopathy and visual field loss following topiramate use for uncontrolled seizures. Such side effects have not been well documented despite the increasing use of topiramate in the past 10 years. A thorough search of available English literature revealed only a small number of reports of topiramate-induced retinopathy or visual field defects in humans. One similar case has been described. We are concerned about the possible rare instances of this occurrence in future patients and hence would like to propose a presumed correlation. A 48-year-old Chinese woman developed blurred vision after 9 months of topiramate use. Her visual acuity dropped from 1.2 to 0.7 in both eyes, with bilateral diffuse pigmentary retinopathy and a constricted visual field. Despite an improvement in visual acuity after cessation of the drug, the other clinical findings remained. The temporal relationship between the initiation of topiramate and the visual disturbance suggests that topiramate could be the cause of such signs and symptoms. Topiramate potentially causes pigmentary retinopathy and constricted visual field.

Advances in understanding and management of retinopathy of prematurity.

PubMed

Hartnett, Mary Elizabeth

The understanding, diagnosis, and treatment of retinopathy of prematurity have changed in the 70 years since the original description of retrolental fibroplasia associated with high oxygenation. It is now recognized that retinopathy of prematurity differs in appearance worldwide and as ever smaller and younger premature infants survive. New methods are being evaluated to image the retina, diagnose severe retinopathy of prematurity, and determine windows of time for treatment to save eyes and improve visual and neural outcomes. New treatments to promote physiologic retinal vascular development, vascular repair, and inhibit vasoproliferation by regulating proteins involved in vascular endothelial growth factor, insulin-like growth factor, or erythropoietin signaling. Reducing excessive oxidative/nitrosative stress and understanding progenitor cells and neurovascular and glial vascular interactions are being studied. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinopathy and Cognitive Impairment in Adults With CKD

PubMed Central

Yaffe, Kristine; Ackerson, Lynn; Hoang, Tina D.; Go, Alan S.; Maguire, Maureen G.; Ying, Gui-Shuang; Daniel, Ebenezer; Bazzano, Lydia A.; Coleman, Martha; Cohen, Debbie L.; Kusek, John W.; Ojo, Akinlolu; Seliger, Stephen; Xie, Dawei; Grunwald, Juan E.

2014-01-01

Background Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small vessel disease. This relationship has not been evaluated among persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. Study Design Cross-sectional study Setting & Participants 588 participants ≥ 52 years old with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study Predictor Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. Outcomes Neuropsychological battery of six cognitive tests Measurements Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy adjusting for age, race, sex, education, and medical comorbidities. Results The mean age of the cohort was 65.3 +/− 5.6 (SD) years; 51.9% were non-White, and 52.6% were male. The prevalence of retinopathy was 30.1% and 14.3% for cognitive impairment. Compared to those without retinopathy, participants with retinopathy had increased likelihood of cognitive impairment on executive function (35.1% vs. 11.5%; OR, 3.4; 95% CI, 2.0-6.0), attention (26.7% vs. 7.3%; OR, 3.0; 95% CI, 1.8-4.9), and naming (26.0% vs. 10.0%; OR, 2.1; 95% CI, 1.2-3.4) after multivariable adjustment. Increased level of retinopathy was also associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. Limitations Unknown temporal relationship between retinopathy and impairment. Conclusions In adults with CKD, retinopathy is

Awareness of diabetic retinopathy among patients with type 2 diabetes mellitus in Jordan.

PubMed

Bakkar, May M; Haddad, Mera F; Gammoh, Yazan S

2017-01-01

Increasing the level of awareness of diabetic retinopathy among individuals with type 2 diabetes mellitus is considered an important factor for early diagnosis and management of diabetic retinopathy. The aim of this study was to evaluate awareness of diabetic retinopathy among a sample of type 2 diabetes mellitus patients in Jordan. The study period was from August to December 2015. The sample was selected randomly from patients with type 2 diabetes mellitus from the general population in three main cities of Jordan (Amman, Irbid, and Zarqa). A questionnaire was distributed to 237 participants with diabetes to assess their awareness and knowledge of diabetes and diabetic retinopathy. The questionnaire included questions to assess awareness about diabetic retinopathy, sources of knowledge about the disease, and patients' knowledge and compliance with available treatments and routine eye examinations. Patients were also questioned about the barriers that may interfere with early eye examination. A total of 237 participants (107 [45.1%] females and 130 [54.9%] males) with type 2 diabetes were interviewed. Mean age±SD for the study population was 54.51±10.28 years. Of the study population, 88.2% were aware that diabetes can affect the eyes and 81% reported that diabetic retinopathy can lead to blindness. Higher level of patients' awareness of diabetic retinopathy was related to higher level of formal education ( p <0.05). The main source of information about diabetic retinopathy as reported by 47.3% patients was general practitioners. Patients' compliance with diabetes management was relatively high; however, their compliance with routine retinal assessment was poor, with only a total of 29.5% of participants having had an eye examination in the previous year. Awareness of the nature and consequences of diabetic retinopathy among patients with diabetes in Jordan is relatively high. However, patients' motivation to undergo retinal assessment was poor in the sample

Outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin.

PubMed

Mehta, Nilesh; Murthy, Uma K; Kaul, Vivek; Alpert, Samuel; Abruzzese, Gerald; Teitelbaum, Charles

2010-02-01

The purpose of this study is to evaluate the incidence and outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin. A total of 74 hepatitis C patients with baseline eye exams and eye exams during therapy were included. Retinopathy was defined as development of cotton wool spots and/or intra-retinal hemorrhage. Demographics, hepatitis C viral characteristics, treatment and laboratory data, and eye exam findings were compared in groups with and without retinopathy. Retinopathy developed in 28 (38%), early in therapy. Pre-treatment eye exams did not predict risk of retinopathy. Therapy was continued in all but one; cotton wool spots resolved in 24 of 26. All nine patients with intra-retinal hemorrhage had resolution. No patient had retinopathy-related visual deterioration. Retinopathy is common with peginterferon therapy, but the outcome is favorable. Cessation of therapy for retinopathy is not warranted. Severe visual disturbances and scotomas deserve further evaluation.

Changes in retinal venular oxygen saturation predict activity of proliferative diabetic retinopathy 3 months after panretinal photocoagulation.

PubMed

Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin; Peto, Tunde; Grauslund, Jakob

2018-03-01

Proliferative diabetic retinopathy (PDR) is a severe blinding condition. We investigated whether retinal metabolism, measured by retinal oximetry, may predict PDR activity after panretinal laser photocoagulation (PRP). We performed a prospective, interventional, clinical study of patients with treatment-naive PDR. Wide-field fluorescein angiography (OPTOS, Optomap) and global and focal retinal oximetry (Oxymap T1) were performed at baseline (BL), and 3 months (3M) after PRP. Angiographic findings were used to divide patients according to progression or non-progression of PDR after PRP. We evaluated differences in global and focal retinal oxygen saturation between patients with and without progression of PDR after PRP treatment. We included 45 eyes of 37 patients (median age and duration of diabetes were 51.6 and 20 years). Eyes with progression of PDR developed a higher retinal venous oxygen saturation than eyes with non-progression at 3M (global: +5.9% (95% CI -1.5 to 12.9), focal: +5.4%, (95% CI -4.1 to 14.8)). Likewise, progression of PDR was associated with a lower arteriovenular (AV) oxygen difference between BL and 3M (global: -6.1%, (95% CI -13.4 to -1.4), focal: -4.5% (95% CI -12.1 to 3.2)). In a multiple logistic regression model, increment in global retinal venular oxygen saturation (OR 1.30 per 1%-point increment, p=0.017) and decrement in AV oxygen saturation difference (OR 0.72 per 1%-point increment, p=0.016) at 3M independently predicted progression of PDR. Development of higher retinal venular and lower AV global oxygen saturation independently predicts progression of PDR despite standard PRP and might be a potential non-invasive marker of angiogenic disease activity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Low-oxygen waters limited habitable space for early animals.

PubMed

Tostevin, R; Wood, R A; Shields, G A; Poulton, S W; Guilbaud, R; Bowyer, F; Penny, A M; He, T; Curtis, A; Hoffmann, K H; Clarkson, M O

2016-09-23

The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550-541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 μM) was a key requirement for the development of early animal-based ecosystems.

A review on exudates detection methods for diabetic retinopathy.

PubMed

Joshi, Shilpa; Karule, P T

2018-01-01

The presence of exudates on the retina is the most characteristic symptom of diabetic retinopathy. As exudates are among early clinical signs of DR, their detection would be an essential asset to the mass screening task and serve as an important step towards automatic grading and monitoring of the disease. Reliable identification and classification of exudates are of inherent interest in an automated diabetic retinopathy screening system. Here we review the numerous early studies that used for automatic exudates detection with the aim of providing decision support in addition to reducing the workload of an ophthalmologist. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of disease stage on progression of hydroxychloroquine retinopathy.

PubMed

Marmor, Michael F; Hu, Julia

2014-09-01

Hydroxychloroquine sulfate retinopathy can progress after the drug is stopped. It is not clear how this relates to the stage of retinopathy or whether early screening with modern imaging technology can prevent progression and visual loss. To determine the relationship between progression of retinopathy and the severity of disease using objective data from optical coherence tomography and assess the value of early screening for the toxic effects of hydroxychloroquine. Clinical findings in patients with hydroxychloroquine retinopathy were monitored with repeated anatomical and functional examinations for 13 to 40 months after the drug was stopped in a referral practice in a university medical center. Eleven patients participated, with the severity of toxic effects categorized as early (patchy parafoveal damage shown on field or objective testing), moderate (a 50%-100% parafoveal ring of optical coherence tomography thinning but intact retinal pigment epithelium), and severe (visible bull's-eye damage). Visual acuity, white 10-2 visual field pattern density plots, fundus autofluorescence, spectral-density optical coherence tomography cross sections, thickness (from cube diagrams), and ellipsoid zone length. Visual acuity and visual fields showed no consistent change. Fundus autofluorescence showed little or no change except in severe cases in which the bull's-eye damage expanded progressively. Optical coherence tomography cross sections showed little visible change in early and moderate cases but progressive foveal thinning (approximately 7 μm/y) and loss of ellipsoid zone (in the range of 100 μm/y) in severe cases, which was confirmed by quantitative measurements. The measurements also showed some foveal thinning (approximately 4 μm/y) and deepening of parafoveal loss in moderate cases, but the breadth of the ellipsoid zone remained constant in both early and moderate cases. A few cases showed a suggestion of ellipsoid zone improvement. Patients with

Altered retinal microRNA expression profiles in early diabetic retinopathy: an in silico analysis.

PubMed

Xiong, Fen; Du, Xinhua; Hu, Jianyan; Li, Tingting; Du, Shanshan; Wu, Qiang

2014-07-01

MicroRNAs (miRNAs) - as negative regulators of target genes - are associated with various human diseases, but their precise role(s) in diabetic retinopathy (DR) remains to be elucidated. The aim of this study was to elucidate the involvement of miRNAs in early DR using in silico analysis to explore their gene expression patterns. We used the streptozotocin (STZ)-induced diabetic rat to investigate the roles of miRNAs in early DR. Retinal miRNA expression profiles from diabetic versus healthy control rats were examined by miRNA array analysis. Based on several bioinformatic systems, specifically, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified signatures of the potential pathological processes, gene functions, and signaling pathways that are influenced by dysregulated miRNAs. We used quantitative real-time polymerase chain reaction (qRT-PCR) to validate six (i.e. those with significant changes in expression levels) of the 17 miRNAs that were detected in the miRNA array. We also describe the significant role of the miRNA-gene network, which is based on the interactions between miRNAs and target genes. GO analysis of the 17 miRNAs detected in the miRNA array analysis revealed the most prevalent miRNAs to be those related to biological processes, olfactory bulb development and axonogenesis. These miRNAs also exert significant influence on additional pathways, including the mitogen-activated protein and calcium signaling pathways. Six of the seventeen miRNAs were chosen for qRT-PCR validation. With the exception of a slight difference in miRNA-350, our results are in close agreement with the differential expressions detected by array analysis. This study, which describes miRNA expression during the early developmental phases of DR, revealed extensive miRNA interactions. Based on both their target genes and signaling pathways, we suggest that miRNAs perform critical regulatory functions during the early stages of DR

Visual cycle modulation in neurovascular retinopathy.

PubMed

Akula, James D; Hansen, Ronald M; Tzekov, Radouil; Favazza, Tara L; Vyhovsky, Tanya C; Benador, Ilan Y; Mocko, Julie A; McGee, David; Kubota, Ryo; Fulton, Anne B

2010-08-01

Rats with oxygen-induced retinopathy (OIR) model the pediatric retinal disease retinopathy of prematurity (ROP). Recent findings in OIR rats imply a causal role for the rods in the ROP disease process, although only experimental manipulation of rod function can establish this role conclusively. Accordingly, a visual cycle modulator (VCM) - with no known direct effect on retinal vasculature - was administered to "50/10 model" OIR Sprague-Dawley rats to test the hypotheses that it would 1) alter rod function and 2) consequently alter vascular outcome. Four litters of pups (N=46) were studied. For two weeks, beginning on postnatal day (P) 7, the first and fourth litters were administered 6 mg kg(-1) N-retinylacetamide (the VCM) intraperitoneally; the second and third litters received vehicle (DMSO) alone. Following a longitudinal design, retinal function was assessed by electroretinography (ERG) and the status of the retinal vessels was monitored using computerized fundus photograph analysis. Rod photoreceptor and post-receptor response amplitudes were significantly higher in VCM-treated than in vehicle-treated rats; deactivation of phototransduction was also significantly more rapid. Notably, the arterioles of VCM-treated rats showed significantly greater recovery from OIR. Presuming that the VCM did not directly affect the retinal vessels, a causal role for the neural retina - particularly the rod photoreceptors - in OIR was confirmed. There was no evidence of negative alteration of photoreceptor function consequent to VCM treatment. This finding implicates the rods as a possible therapeutic target in neurovascular diseases such as ROP. Copyright 2010 Elsevier Ltd. All rights reserved.

Role of endoplasmic reticulum stress in 12/15-lipoxygenase-induced retinal microvascular dysfunction in a mouse model of diabetic retinopathy.

PubMed

Elmasry, Khaled; Ibrahim, Ahmed S; Saleh, Heba; Elsherbiny, Nehal; Elshafey, Sally; Hussein, Khaled A; Al-Shabrawey, Mohamed

2018-05-01

Our earlier studies have established the role of 12/15-lipoxygenase (LO) in mediating the inflammatory reaction in diabetic retinopathy. However, the exact mechanism is still unclear. The goal of the current study was to identify the potential role of endoplasmic reticulum (ER) stress as a major cellular stress response in the 12/15-LO-induced retinal changes in diabetic retinopathy. We used in vivo and in vitro approaches. For in vivo studies, experimental diabetes was induced in wild-type (WT) mice and 12/15-Lo (also known as Alox15) knockout mice (12/15-Lo -/- ); ER stress was then evaluated after 12-14 weeks of diabetes. We also tested the effect of intravitreal injection of 12-hydroxyeicosatetraenoic acid (HETE) on retinal ER stress in WT mice and in mice lacking the catalytic subunit of NADPH oxidase, encoded by Nox2 (also known as Cybb) (Nox2 -/- mice). In vitro studies were performed using human retinal endothelial cells (HRECs) treated with 15-HETE (0.1 μmol/l) or vehicle, with or without ER stress or NADPH oxidase inhibitors. This was followed by evaluation of ER stress response, NADPH oxidase expression/activity and the levels of phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) by western blotting and immunoprecipitation assays. Moreover, real-time imaging of intracellular calcium (Ca 2+ ) release in HRECs treated with or without 15-HETE was performed using confocal microscopy. Deletion of 12/15-Lo significantly attenuated diabetes-induced ER stress in mouse retina. In vitro, 15-HETE upregulated ER stress markers such as phosphorylated RNA-dependent protein kinase-like ER-regulated kinase (p-PERK), activating transcription factor 6 (ATF6) and protein disulfide isomerase (PDI) in HRECs. Inhibition of ER stress reduced 15-HETE-induced-leucocyte adhesion, VEGFR2 phosphorylation and NADPH oxidase expression/activity. However, inhibition of NADPH oxidase or deletion of Nox2 had no effect on ER stress induced by the 12/15-LO

Early Cambrian oxygen minimum zone-like conditions at Chengjiang

NASA Astrophysics Data System (ADS)

Hammarlund, Emma U.; Gaines, Robert R.; Prokopenko, Maria G.; Qi, Changshi; Hou, Xian-Guang; Canfield, Donald E.

2017-10-01

The early Cambrian succession at Chengjiang contains the most diverse Cambrian fossil assemblage yet described, and contributes significantly to our understanding of the diversification of metazoans in the Cambrian ;explosion;. The Cambrian Period occupies a transitional episode of global ocean chemistry, following the oxygenation of the surface ocean and of shallow marine environments during the Ediacaran Period, but prior to the establishment of a predominantly oxygenated deep ocean in the mid-Paleozoic. Despite recent attention, a detailed understanding of the chemical conditions that prevailed in early Cambrian marine settings and the relationship of those conditions to early metazoan ecosystems is still emerging. Here, we report multi-proxy geochemical data from two drill cores through the early Cambrian (Series 2) Yu'anshan Formation of Yunnan, China. Results reveal dynamic water-column chemistry within the succession, which progressively shifted from euxinic to oxic conditions during deposition of the Yu'anshan Formation. The Chengjiang biota occurs in strata that appear to have been deposited under an oxygen-depleted water column that may have supported denitrification, as in modern oxygen-minimum zones. The oxygenated benthic environments in which the Chengjiang biota thrived were proximal to, but sharply separated from, the open ocean by a persistent anoxic water mass that occupied a portion of the outer shelf. Oxygen depletion in the lower water column developed dynamically in response to nutrient availability and possibly at lower thresholds of productivity due to lower atmospheric oxygen concentrations in Cambrian. These findings suggest that the frequent development of oxygen-limiting conditions in continental margin settings provided an environmental barrier that may have affected biogeographic, ecological and evolutionary development of early metazoan communities.

The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Jeong A.

Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) ormore » modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC. - Highlights: • The effects of riluzole were examined in streptozotocin-induced diabetic mice. • The diameter of retinal vessels and the number of pericytes were severely reduced. • The levels of MCP1 and PKC were increased, while riluzole reversed all changes. • Riluzole attenuated the level of MCP1 in AGE- or mLDL-treated retinal pericytes. • Riluzole attenuated both MCP1 induction and pericyte loss in diabetic retinopathy.« less

An automated retinal imaging method for the early diagnosis of diabetic retinopathy.

PubMed

Franklin, S Wilfred; Rajan, S Edward

2013-01-01

Diabetic retinopathy is a microvascular complication of long-term diabetes and is the major cause for eyesight loss due to changes in blood vessels of the retina. Major vision loss due to diabetic retinopathy is highly preventable with regular screening and timely intervention at the earlier stages. Retinal blood vessel segmentation methods help to identify the successive stages of such sight threatening diseases like diabetes. To develop and test a novel retinal imaging method which segments the blood vessels automatically from retinal images, which helps the ophthalmologists in the diagnosis and follow-up of diabetic retinopathy. This method segments each image pixel as vessel or nonvessel, which in turn, used for automatic recognition of the vasculature in retinal images. Retinal blood vessels were identified by means of a multilayer perceptron neural network, for which the inputs were derived from the Gabor and moment invariants-based features. Back propagation algorithm, which provides an efficient technique to change the weights in a feed forward network, is utilized in our method. Quantitative results of sensitivity, specificity and predictive values were obtained in our method and the measured accuracy of our segmentation algorithm was 95.3%, which is better than that presented by state-of-the-art approaches. The evaluation procedure used and the demonstrated effectiveness of our automated retinal imaging method proves itself as the most powerful tool to diagnose diabetic retinopathy in the earlier stages.

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

NASA Astrophysics Data System (ADS)

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.

Ultrastructure of neurovascular changes in human diabetic retinopathy.

PubMed

Fehér, János; Taurone, Samanta; Spoletini, Marialuisa; Biró, Zsolt; Varsányi, Balázs; Scuderi, Gianluca; Orlando, Maria Patrizia; Turchetta, Rosaria; Micera, Alessandra; Artico, Marco

2018-01-01

The previous concept regarding diabetic retinopathy assigned a primary role to hyperglycemia-induced microvascular alterations, while neuronal and glial abnormalities were considered to be secondary to either ischemia or exudation. The aim of this study was to reveal the potential role of neuronal and glial cells in initial and advanced alterations of the retinopathy in human type 2 diabetes. Electron microscopy and histochemical studies were performed on 38 surgically removed human eyes (28 obtained from diabetic patients and 10 from non-diabetic patients). Morphometric analysis of basement membrane material and lipids was performed. An accumulation of metabolic by-products was found in the capillary wall with aging: this aspect was significantly more pronounced in diabetics. Müller glial cells were found to contribute to alterations of the capillary wall and to occlusion, as well as to the development of proliferative retinopathy and cystoid degeneration of the retina. Our results showed morphological evidence regarding the role of neuronal and glial cells in the pathology of diabetic retinopathy, prior and in addition to microangiopathy. These morphological findings support a neurovascular pathogenesis at the origin of diabetic retinopathy, thus the current treatment approach should be completed by neuroprotective measures.

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside

PubMed Central

Blindbæk, Søren Leer; Torp, Thomas Lee; Lundberg, Kristian; Soelberg, Kerstin; Vergmann, Anna Stage; Poulsen, Christina Døfler; Frydkjaer-Olsen, Ulrik; Broe, Rebecca; Rasmussen, Malin Lundberg; Wied, Jimmi; Lind, Majbrit; Vestergaard, Anders Højslet; Peto, Tunde

2017-01-01

The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes. PMID:28491870

Visual acuity at 10 years in Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study eyes: effect of retinal residua of retinopathy of prematurity.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty

2006-02-01

To describe recognition (letter) acuity at age 10 years in eyes with and without retinal residua of retinopathy of prematurity (ROP). Presence and severity of ROP residua were documented by a study ophthalmologist. Masked testers measured monocular recognition visual acuity (Early Treatment of Diabetic Retinopathy Study) when the children were 10 years old. Two hundred forty-seven of 255 surviving Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) randomized trial patients participated. A reference group of 102 of 104 Philadelphia-based CRYO-ROP study participants who did not develop ROP was also tested. More severe retinal residua were associated with worse visual acuity, regardless of whether retinal ablation was performed to treat the severe acute-phase ROP. However, within each ROP residua category, there was a wide range of visual acuity results. This is the first report of the relation between visual acuity (Early Treatment of Diabetic Retinopathy Study charts) and structural abnormalities related to ROP in a large group of eyes that developed threshold ROP in the perinatal period. Visual deficits are greater in eyes with more severe retinal residua than in eyes with mild or no residua. However, severity of ROP residua does not predict the visual acuity of an individual eye because within a single residua category, acuity may range from near normal to blind.

Glycogen synthase kinase-3: a key kinase in retinal neuron apoptosis in early diabetic retinopathy.

PubMed

Li, Zhaohui; Ma, Ling; Chen, Xiaodong; Li, Yonghao; Li, Shiyi; Zhang, Jinglin; Lu, Lin

2014-01-01

Diabetes-related pathogenic factors can cause retinal ganglion cell (RGC) apoptosis, but the specific mechanism is not very clear. The aim of this study is to investigate the correlation between glycogen synthase kinase-3 (GSK-3) activation and retinal neuron apoptosis. In an in vitro experiment, the number of apoptotic RGC-5 cells differentiated by staurosporine was evaluated via flow cytometry and nuclei staining using Hoechst 33258. GSK-3 phosphorylation and caspase-3 activation in RGC-5 cells after serum deprivation were determined using Western blotting. Mitochondrial membrane potential was detected using the dye 5, 5', 6, 6'tetrachloro-1, 1', 3, 3'-tetrethyl benzimidalyl carbocyanine iodide, and reactive oxygen species (ROS) levels were measured with dihydroethidium. In an in vivo experiment, the number of apoptotic retinal neurons was evaluated via terminal transferase dUTP nick-end labeling (TUNEL), and GSK-3 phosphorylation was determined using Western blotting, in the retinal nerve epithelial tissue of rats in which diabetes was induced by intravenous tail-vein injection of streptozotocin for 4 weeks. The levels of phosphorylated Ser21/9 in GSK-3α/β and p-T308/S473-AKT were lower and the cleaved caspase-3 levels were higher in the serum-deprived model (P < 0.05). Lithium chloride treatment was associated with a slower rate of apoptosis, increased mitochondrial membrane potential, and decreased ROS levels in differentiated RGC-5 cells (P < 0.05). The level of blood glucose and the number of TUNEL-positive cells in the whole-mounted retinas were higher (P < 0.01), and the levels of phosphorylated Ser21/9 in GSK-3α/β and body weight were lower (P < 0.05). However, the thickness of the retinal nerve epithelial layer was not significantly less in diabetic rats compared with control group. Lithium chloride intravitreal injection increased the levels of phosphorylated Ser21/9 in GSK-3α/β and decreased TUNEL-positive cells in the whole-mounted retinas. GSK

Final visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Good, William V; Hardy, Robert J; Dobson, Velma; Palmer, Earl A; Phelps, Dale L; Tung, Betty; Redford, Maryann

2010-06-01

To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk prethreshold retinopathy of prematurity (ROP) with conventionally managed eyes. Infants with symmetrical, high-risk prethreshold ROP (n = 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.3% vs 28.6% [corrected] unfavorable outcome; P = .15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P = .02) treated early but not Type 2 eyes (23.6% vs 19.4%; P = .37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P < .001), with no greater risk of ocular complications. Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Screening of diabetics for retinopathy by ophthalmic opticians.

PubMed Central

Burns-Cox, C J; Hart, J C

1985-01-01

Diabetes mellitus is a major cause of blindness in England and Wales in those aged between 30 and 64. Photocoagulation can frequently prevent blindness provided the retinopathy is detected at an appropriate stage but unfortunately the benefits are small if the changes are advanced. Early detection of diabetic retinopathy by regular examination is needed. We have shown that ophthalmic opticians have the skill to detect retinal changes at a treatable stage. Out of 844 eye checks, 80 were reported by ophthalmic opticians to justify referral to an ophthalmologist and 20 of these required photocoagulation treatment. Of a sample of 197 patients rechecked by an ophthalmologist reported by ophthalmic opticians not to justify referral, only one needed treatment. With local agreement this system of detecting retinopathy could be easily applied anywhere in the United Kingdom. No extra personnel or facilities are needed. PMID:3921106

Screening of diabetics for retinopathy by ophthalmic opticians.

PubMed

Burns-Cox, C J; Hart, J C

1985-04-06

Diabetes mellitus is a major cause of blindness in England and Wales in those aged between 30 and 64. Photocoagulation can frequently prevent blindness provided the retinopathy is detected at an appropriate stage but unfortunately the benefits are small if the changes are advanced. Early detection of diabetic retinopathy by regular examination is needed. We have shown that ophthalmic opticians have the skill to detect retinal changes at a treatable stage. Out of 844 eye checks, 80 were reported by ophthalmic opticians to justify referral to an ophthalmologist and 20 of these required photocoagulation treatment. Of a sample of 197 patients rechecked by an ophthalmologist reported by ophthalmic opticians not to justify referral, only one needed treatment. With local agreement this system of detecting retinopathy could be easily applied anywhere in the United Kingdom. No extra personnel or facilities are needed.

An automated approach for early detection of diabetic retinopathy using SD-OCT images.

PubMed

ElTanboly, Ahmed H; Palacio, Agustina; Shalaby, Ahmed M; Switala, Andrew E; Helmy, Omar; Schaal, Shlomit; El-Baz, Ayman

2018-01-01

  This study was to demonstrate the feasibility of an automatic approach for early detection of diabetic retinopathy (DR) from SD-OCT images. These scans were prospectively collected from 200 subjects through the fovea then were automatically segmented, into 12 layers. Each layer was characterized by its thickness, tortuosity, and normalized reflectivity. 26 diabetic patients, without DR changes visible by funduscopic examination, were matched with 26 controls, according to age and sex, for purposes of statistical analysis using mixed effects ANOVA. The INL was narrower in diabetes (p = 0.14), while the NFL (p = 0.04) and IZ (p = 0.34) were thicker. Tortuosity of layers NFL through the OPL was greater in diabetes (all p < 0.1), while significantly greater normalized reflectivity was observed in the MZ and OPR (both p < 0.01) as well as ELM and IZ (both p < 0.5). A novel automated method enables to provide quantitative analysis of the changes in each layer of the retina that occur with diabetes. In turn, carries the promise to a reliable non-invasive diagnostic tool for early detection of DR.

Recessive Stargardt Disease Phenocopying Hydroxychloroquine Retinopathy

PubMed Central

Noupuu, Kalev; Lee, Winston; Zernant, Jana; Greenstein, Vivienne C.; Tsang, Stephen; Allikmets, Rando

2015-01-01

Purpose To describe a series of Stargardt disease (STGD1) patients exhibiting a phenotype usually associated with hydroxychloroquine (HCQ) retinopathy on spectral domain-optical coherence tomography (SD-OCT). Methods Observational case series from Columbia University Medical Center involving 8 patients with genetically-confirmed STGD1. Patients selected for the study presented no history of HCQ use. Horizontal macular SD-OCT scans and accompanying 488nm autofluorescence (AF) images, color fundus photographs, and full-field electroretinograms were analyzed. Results All study patients exhibited an abrupt thinning of the parafoveal region or disruption of the outer retinal layers on SD-OCT resembling the transient HCQ retinopathy phenotype. Funduscopy and AF imaging revealed variations of bull’s eye maculopathy (BEM). Five patients exhibited local fleck-like deposits around the lesion. Genetic screening confirmed two disease-causing ABCA4 mutations in 5 patients and one mutation in 3 patients. Conclusions A transient SD- OCT phenotype ascribed to patients with HCQ retinopathy is associated with an early subtype of STGD1. This finding may also present with HCQ retinopathy-like BEM lesions on AF imaging and funduscopy. A phenotypic overlap may not be surprising given certain shared mechanistic disease processes between the two conditions. A thorough work-up, including screening of genes that are causal in retinal dystrophies associated with foveal sparing, may prevent the misdiagnoses of more ambiguous cases. PMID:26311262

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.

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

PubMed

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

2015-01-01

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. 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. 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). 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.

Photoluminescence due to early stage of oxygen precipitation in multicrystalline Si for solar cells

NASA Astrophysics Data System (ADS)

Higuchi, Fumito; Tajima, Michio; Ogura, Atsushi

2017-07-01

To analyze the early stage of oxygen precipitation in n-type multicrytalline Si, the spectral change of photoluminescence (PL) induced by thermal treatment at 450-650 °C was investigated in relation to the changes in excess donor and interstitial oxygen concentrations. We observed the characteristic PL bands in the near-band-edge region and sharp lines in the deep-level region in correspondence with the generation of thermal donors and new donors. The observed PL spectral variation is essentially the same as that in Czochralski-grown Si annealed at 450-650 °C.

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

PubMed

Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

2018-02-01

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

Decision support system for diabetic retinopathy using discrete wavelet transform.

PubMed

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

2013-03-01

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

Retinal changes in diabetic patients without diabetic retinopathy.

PubMed

Dumitrescu, Alina Gabriela; Istrate, Sinziana Luminita; Iancu, Raluca Claudia; Guta, Oana Maria; Ciuluvica, Radu; Voinea, Liliana

2017-01-01

The purpose of this study was to measure retinal vessel caliber and to examine early changes in macular thickness using optical coherence tomography (OCT). We evaluated to what extend vascular caliber and macular thickness differed between patients with type 2 diabetes mellitus without diabetic retinopathy compared with healthy individuals. 26 diabetic patients without diabetic retinopathy and 26 normal participants without any retinal and optic nerve diseases underwent ophthalmic examination, fundus photography, and OCT imaging. Temporal inferior retinal vessel diameters were measured using OCT. Also, we measured macular thickness in nine ETDRS subfields using Cirrus OCT. The mean age in the diabetic group was 61.5 years and in the control group, 55.5 years. Wider retinal arterioles and venules were found in patients with diabetes compared with healthy subjects (120 µm versus 96 µm, p<0.005 and 137 µm versus 120.5 µm, p value <0.001, respectively). In patients with type 2 diabetes mellitus, central macular thickness was significantly thinner than that of control eyes (243.5 µm versus 269.9 µm, p value <0.001). Our results support the hypothesis that the association between vascular damage and structural changes of the neuroretina is an early indicator of retinal impairment in patients with diabetes without diabetic retinopathy.

The worldwide epidemic of diabetic retinopathy

PubMed Central

Zheng, Yingfeng; He, Mingguang; Congdon, Nathan

2012-01-01

Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a significant impact on the world's health systems. Globally, the number of people with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and we estimate that the number with vision-threatening diabetic retinopathy (VTDR) will increase from 37.3 million to 56.3 million, if prompt action is not taken. Despite growing evidence documenting the effectiveness of routine DR screening and early treatment, DR frequently leads to poor visual functioning and represents the leading cause of blindness in working-age populations. DR has been neglected in health-care research and planning in many low-income countries, where access to trained eye-care professionals and tertiary eye-care services may be inadequate. Demand for, as well as, supply of services may be a problem. Rates of compliance with diabetes medications and annual eye examinations may be low, the reasons for which are multifactorial. Innovative and comprehensive approaches are needed to reduce the risk of vision loss by prompt diagnosis and early treatment of VTDR. PMID:22944754

The worldwide epidemic of diabetic retinopathy.

PubMed

Zheng, Yingfeng; He, Mingguang; Congdon, Nathan

2012-01-01

Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a significant impact on the world's health systems. Globally, the number of people with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and we estimate that the number with vision-threatening diabetic retinopathy (VTDR) will increase from 37.3 million to 56.3 million, if prompt action is not taken. Despite growing evidence documenting the effectiveness of routine DR screening and early treatment, DR frequently leads to poor visual functioning and represents the leading cause of blindness in working-age populations. DR has been neglected in health-care research and planning in many low-income countries, where access to trained eye-care professionals and tertiary eye-care services may be inadequate. Demand for, as well as, supply of services may be a problem. Rates of compliance with diabetes medications and annual eye examinations may be low, the reasons for which are multifactorial. Innovative and comprehensive approaches are needed to reduce the risk of vision loss by prompt diagnosis and early treatment of VTDR.

The Diabetic Retinopathy Screening Workflow

PubMed Central

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

2015-01-01

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

Delayed progression of diabetic cataractogenesis and retinopathy by Litchi chinensis in STZ-induced diabetic rats.

PubMed

Kilari, Eswar Kumar; Putta, Swathi

2017-03-01

The study was carried out to evaluate the effect of the aqueous fruit pericarp extract of Litchi chinensis (APLC) on parameters which leads to diabetic cataractogenesis and retinopathy in the streptozotocin-induced diabetic rats. The objective of the study is to evaluate the APLC for in vivo antioxidant activity and its role in inhibiting the polyol pathway and formation of advanced glycation end products (AGEs). The diabetic animals were treated with L. chinensis for a period of 12 weeks. At the end of 12 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress by protein content, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and polyolpathway by aldose reductase (AR) in lens homogenates, alterations in protein carbonyl content (PCO) and AGEs in both serum and lens the APLC-treated diabetic rats were compared against diabetic control rats. Cataract progression due to hyperglycemia was monitored by slit lamp bio microscope and classified into four stages. Fundoscope test and retinal histopathology were done for assessing retinopathy. Statistically significant reduction in glucose, and elevation of protein content, SOD, CAT, and GSH levels and decreased levels of AR and PCO in lens homogenate and significant reduction in AGEs serum and lens homogenate were observed. Slit lamp examination, fundoscope, and histopathology showed improvement in retinal changes in APLC-treated rats compared to diabetic control animals. The treatment with APLC found to delay the progression of diabetic cataractogenesis and retinopathy, which might be due to its antioxidant activity, because of the presence of active phytochemicals in APLC.

Role of VEGF Inhibition in the Treatment of Retinopathy of Prematurity.

PubMed

Eldweik, Luai; Mantagos, Iason S

2016-01-01

Retinopathy of prematurity (ROP) is a potentially blinding disease characterized by retinal neovascularization, which eventually can lead to tractional retinal detachment. Improvements have been made regarding the management of retinopathy of prematurity (ROP) since it was described in the Cryotherapy for Retinopathy of Prematurity study. A more appropriate time for therapeutic intervention was defined by the Early Treatment for Retinopathy of Prematurity (ETROP) trial. Advances in screening strategies with the use of digital imaging systems are now available. All of this and the use of laser photocoagulation and vitreoretinal surgery have contributed to significant increases in favorable outcomes and decreases in child blindness secondary to ROP. Recently the use of vascular endothelial growth factor (VEGF) inhibitors has been introduced to the armamentarium for the treatment of ROP. The purpose of this review article is to evaluate the role of VEGF inhibition in the treatment of ROP.

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley

Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice.

PubMed

Saliba, Alexandra; Du, Yunpeng; Liu, Haitao; Patel, Shyam; Roberts, Robin; Berkowitz, Bruce A; Kern, Timothy S

2015-01-01

Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in retinas of albino rats. Here, we test the hypothesis that photobiomodulation (PBM) is effective in diabetic, pigmented mice, even when delayed until weeks after onset of diabetes. Direct and indirect effects of PBM on the retina also were studied. Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm) daily. In one study, mice were diabetic for 4 weeks before initiation of PBM for an additional 10 weeks. Retinal oxidative stress, inflammation, and retinal function were measured. In some mice, heads were covered with a lead shield during PBM to prevent direct illumination of the eye, or animals were treated with an inhibitor of heme oxygenase-1. In a second study, PBM was initiated immediately after onset of diabetes, and administered daily for 2 months. These mice were examined using manganese-enhanced MRI to assess effects of PBM on transretinal calcium channel function in vivo. PBM intervention improved diabetes-induced changes in superoxide generation, leukostasis, expression of ICAM-1, and visual performance. PBM acted in part remotely from the retina because the beneficial effects were achieved even with the head shielded from the light therapy, and because leukocyte-mediated cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers. PBM induces retinal protection against abnormalities induced by diabetes in pigmented animals, and even as an intervention. Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms. PBM is a novel non-pharmacologic treatment strategy to inhibit early changes of diabetic retinopathy.

New Ways to Detect Pediatric Sickle Cell Retinopathy: A Comprehensive Review.

PubMed

Pahl, Daniel A; Green, Nancy S; Bhatia, Monica; Chen, Royce W S

2017-11-01

Sickle retinopathy reflects disease-related vascular injury of the eye, which can potentially result in visual loss from vitreous hemorrhage or retinal detachment. Here we review sickle retinopathy among children with sickle cell disease, describe the epidemiology, pediatric risk factors, pathophysiology, ocular findings, and treatment. Newer, more sensitive ophthalmological imaging modalities are available for retinal imaging, including ultra-widefield fluorescein angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Optical coherence tomography angiography provides a noninvasive view of retinal vascular layers that could previously not be imaged and can be quantified for comparative or prospective analyses. Ultra-widefield fluorescein angiography provides a more comprehensive view of the peripheral retina than traditional imaging techniques. Screening for retinopathy by standard fundoscopic imaging modalities detects a prevalence of approximately 10%. In contrast, these more sensitive methods allow for more sensitive examination that includes the retina perimeter where sickle retinopathy is often first detectable. Use of these new imaging modalities may detect a higher prevalence of early sickle pathology among children than has previously been reported. Earlier detection may help in better understanding the pathogenesis of sickle retinopathy and guide future screening and treatment paradigms.

Delay in diabetic retinopathy screening increases the rate of detection of referable diabetic retinopathy.

PubMed

Scanlon, P H; Aldington, S J; Stratton, I M

2014-04-01

To assess whether there is a relationship between delay in retinopathy screening after diagnosis of type 2 diabetes and level of retinopathy detected. Patients were referred from 88 primary care practices to an English National Health Service diabetic eye screening programme. Data for screened patients were extracted from the primary care databases using semi-automated data collection algorithms supplemented by validation processes. The programme uses two-field mydriatic digital photographs graded by a quality assured team. Data were available for 8183 screened patients with diabetes newly diagnosed in 2005, 2006 or 2007. Only 163 with type 1 diabetes were identified and were insufficient for analysis. Data were available for 8020 with newly diagnosed type 2 diabetes. Of these, 3569 were screened within 6 months, 2361 between 6 and 11 months, 1058 between 12 and 17 months, 366 between 18 and 23 months, 428 between 24 and 35 months, and 238 at 3 years or more after diagnosis. There were 5416 (67.5%) graded with no retinopathy, 1629 (20.3%) with background retinopathy in one eye, 753 (9.4%) with background retinopathy in both eyes and 222 (2.8%) had referable diabetic retinopathy. There was a significant trend (P = 0.0004) relating time from diagnosis to screening detecting worsening retinopathy. Of those screened within 6 months of diagnosis, 2.3% had referable retinopathy and, 3 years or more after diagnosis, 4.2% had referable retinopathy. The rate of detection of referable diabetic retinopathy is elevated in those who were not screened promptly after diagnosis of type 2 diabetes. © 2013 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Asymmetric severity of diabetic retinopathy in Waardenburg syndrome.

PubMed

Kashima, Tomoyuki; Akiyama, Hideo; Kishi, Shoji

2011-01-01

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

Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy.

PubMed

Behl, Tapan; Velpandian, Thirumurthy; Kotwani, Anita

2017-05-01

The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

PubMed Central

Dellis, Athanasios; Papatsoris, Athanasios; Kalentzos, Vasileios; Deliveliotis, Charalambos; Skolarikos, Andreas

2017-01-01

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option. PMID:28338304

Macrophage Metalloelastase (MMP-12) Deficiency Mitigates Retinal Inflammation and Pathological Angiogenesis in Ischemic Retinopathy

PubMed Central

Li, Jingming; Wang, Joshua J.; Peng, Qisheng; Chen, Chen; Humphrey, Mary Beth; Heinecke, Jay; Zhang, Sarah X.

2012-01-01

Pathological angiogenesis is a major cause of vision loss in ischemic and inflammatory retinal diseases. Recent evidence implicates macrophage metalloelastase (MMP-12), a macrophage-derived elastinolytic protease in inflammation, tissue remodeling and angiogenesis. However, little is known about the role of MMP-12 in retinal pathophysiology. The present study aims to explore the enzyme’s contributions to retinal angiogenesis in oxygen-induced retinopathy (OIR) using MMP-12 knockout (KO) mice. We find that MMP-12 expression was upregulated in OIR, accompanied by elevated macrophage infiltration and increased inflammatory markers. Compared to wildtype mice, MMP-12 KO mice had decreased levels of adhesion molecule and inflammatory cytokines and reduced vascular leakage in OIR. Concomitantly, these mice had markedly reduced macrophage content in the retina with impaired macrophage migratory capacity. Significantly, loss of MMP-12 attenuated retinal capillary dropout in early OIR and mitigated pathological retinal neovascularization (NV). Similar results were observed in the study using MMP408, a pharmacological inhibitor of MMP-12. Intriguingly, in contrast to reducing pathological angiogenesis, lack of MMP-12 accelerated revascularization of avascular retina in OIR. Taken together, we conclude that MMP-12 is a key regulator of macrophage infiltration and inflammation, contributing to retinal vascular dysfunction and pathological angiogenesis. PMID:23285156

[Outcomes of surgical management of retinopathy of prematurity--an overview].

PubMed

Kuprjanowicz, Leszek; Kubasik-Kładna, Katarzyna; Modrzejewska, Monika

2014-01-01

According to the guidelines by the ETROP (Early Treatment for Retinopathy of Prematurity) study group, laser therapy is the gold standard in the treatment of retinopathy of prematurity. However, progression of the disease is seen in 12% of eyes despite the treatment. Since there is no causal treatment, new therapies of retinopathy of prematurity, are continually sought, such as anti-VEGF agents, beta-blockers, or insulin-like growth factor gene therapy. In cases with concomitant retinal detachment, surgery is performed. The standard therapy for retinopathy of prematurity stages 4-5 involves pars plicata vitrectomy and lensectomy (stage 5), ab externo surgery (scleral buckling) and lens-sparing vitrectomy (some cases of stage 4). Classic vitrectomy with lensectomy is reserved only for cases with advanced retinal tractions, retina-lens apposition or for cases of intraoperative lens damage during the lens-sparing vitrectomy. The ab externo surgery does not eliminate vitreous tractions, but it stabilises the neovascular membrane activity (transforming it into a scar). The indication for this type of operation is stage 4 retinopathy of prematurity with peripheral proliferations, except for the posterior--aggressive form of retinopathy of prematurity. Many papers have been published on combined therapy involving vitrectomy and conservative treatment. In conclusion, optimal timing of surgical intervention is difficult to determine in stages 4 and 5, because the anatomical and functional outcomes in stage 5 are unfavourable. Both, ab externo surgery and vitrectomy tend to produce poor macular vision in eyes with advanced retinopathy of prematurity, therefore surgical intervention at stage 4 just before the local macular retinal detachment provides better anatomical and functional outcomes.

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

PubMed Central

Park, Young Gun; Roh, Young-Jung

2016-01-01

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

Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme.

PubMed

Looker, H C; Nyangoma, S O; Cromie, D T; Olson, J A; Leese, G P; Philip, S; Black, M W; Doig, J; Lee, N; Briggs, A; Hothersall, E J; Morris, A D; Lindsay, R S; McKnight, J A; Pearson, D W M; Sattar, N A; Wild, S H; McKeigue, P; Colhoun, H M

2013-08-01

The aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening. This was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy. The study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years. Transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.

Does bariatric surgery prevent progression of diabetic retinopathy?

PubMed

Chen, Y; Laybourne, J P; Sandinha, M T; de Alwis, N M W; Avery, P; Steel, D H

2017-08-01

PurposeTo assess the changes in diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients post bariatric surgery and report on the risk factors that may be associated with it.Patients and methodsRetrospective observational study of T2DM patients who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2015. Preoperative and postoperative weight, HbA1c, and annual DR screening results were collected from medical records. Patients with preoperative retinal screening and at least one postoperative retinal screening were eligible for analysis. Multivariate analysis was used to explore significant clinical predictors on postoperative worsening in DR.ResultsA total of 102 patients were eligible for analysis and were followed up for 4 years. Preoperatively, 68% of patients had no DR compared to 30% with background retinopathy, 1% pre-proliferative retinopathy, and 1% proliferative retinopathy. In the first postoperative visit, 19% of patients developed new DR compared to 70% stable and 11% improved. These proportions remained similar for each postoperative visit over time. Young age, male gender, high preoperative HbA1c, and presence of preoperative retinopathy were the significant predictors of worsening postoperatively.ConclusionBariatric surgery does not prevent progression of DR. Young male patients with pre-existing DR and poor preoperative glycaemic control are most at risk of progression. All diabetic patients should attend regular DR screening post bariatric surgery to allow early detection of potentially sight-threatening changes, particularly among those with identifiable risk factors. Future prospective studies with prolonged follow-up are required to clarify the duration of risk.

Post-hypoxic constriction of retinal arterioles is impaired during nitric oxide and cyclo-oxygenase inhibition and in diabetic patients without retinopathy.

PubMed

Petersen, Line; Bek, Toke

2017-10-01

Occlusion of retinal vessels leads to retinal ischaemia and hypoxia, which induces vasodilatation in adjacent retinal areas in order to normalize retinal oxygenation. Previous studies have shown that NO and COX products are involved in hypoxia-induced dilatation of retinal arterioles in vitro and in vivo, and that this response is disturbed in patients with diabetes mellitus. However, it is unknown to what extent post-hypoxic recovery of the diameter of retinal arterioles depends on NO and COX products in normal persons and in diabetic patients. The Dynamic Vessel Analyzer (DVA) was used to study the post-hypoxic diameter changes of larger retinal vessels in 20 normal persons, 20 diabetic patients without diabetic retinopathy, and in 18 patients with diabetic maculopathy before and after inhibition of the synthesis of nitric oxide and COX products. In normal persons, the arterioles had re-constricted (p > 0.99) 2 minutes after termination of hypoxia in the absence of antagonists, but not after treatment with L-NMMA and diclofenac (p < 0.01 for all comparisons). In diabetic patients without retinopathy, the arterioles showed no diameter changes after termination of hypoxia during any of the interventions. In patients with diabetic maculopathy hypoxia had not dilated retinal arterioles (p > 0.1 for all comparisons) to allow the study of re-constriction. In all groups, the dilatation of venules remained significantly increased during the post-hypoxic observation period, both in the absence and in the presence of L-NMMA and diclofenac.Post-hypoxic constriction of retinal arterioles depends on NO and COX products, and is impaired in diabetic patients before the development of retinopathy. This disturbance may contribute to the development of diabetic retinopathy, and should be the target of future interventional studies aimed at preventing and treating the disease.ClinicalTrials.gov identifier: NCT01689090.

VASCULAR ABNORMALITIES IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WIDEFIELD IMAGING.

PubMed

Schaal, Karen B; Munk, Marion R; Wyssmueller, Iris; Berger, Lieselotte E; Zinkernagel, Martin S; Wolf, Sebastian

2017-11-10

To detect vascular abnormalities in diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) widefield images, and to compare the findings with color fundus photographs (CFPs) using Early Treatment Diabetic Retinopathy Study severity grading. 3 mm × 3 mm and 12 mm × 12 mm scans were acquired to cover 70° to 80° of the posterior pole using a 100-kHz SS-OCTA instrument. Two masked graders assessed the presence of vascular abnormalities on SS-OCTA and the Early Treatment Diabetic Retinopathy Study level on CFP. The grading results were then compared. A total of 120 diabetic eyes (60 patients) were imaged with the SS-OCTA instrument. Cohort 1 (91 eyes; SS-OCTA grading only) showed microaneurysms in 91% (n = 83), intraretinal microvascular abnormalities in 79% (n = 72), and neovascularization in 21% (n = 19) of cases. Cohort 2 (52 eyes; CFP grading compared with SS-OCTA) showed microaneurysms on CFP in 90% (n = 47) and on SS-OCTA in 96% (n = 50) of cases. Agreement in intraretinal microvascular abnormality detection was fair (k = 0.2). Swept-source optical coherence tomography angiography detected 50% of intraretinal microvascular abnormality cases (n = 26), which were missed on CFP. Agreement in detecting neovascularization was moderate (k = 0.5). Agreement in detection of diabetic retinopathy features on CFP and SS-OCTA varies depending on the vascular changes examined. Swept-source optical coherence tomography angiography shows a higher detection rate of intraretinal microvascular abnormalities (P = 0.039), compared with Early Treatment Diabetic Retinopathy Study grading.

Ultrawide-field Fluorescein Angiography for Evaluation of Diabetic Retinopathy

PubMed Central

Kong, Mingui; Lee, Mee Yon

2012-01-01

Purpose To investigate the advantages of ultrawide-field fluorescein angiography (FA) over the standard fundus examination in the evaluation of diabetic retinopathy (DR). Methods Ultrawide-field FAs were obtained in 118 eyes of 59 diabetic patients; 11 eyes with no DR, 71 eyes with nonproliferative diabetic retinopathy (NPDR), and 36 eyes with proliferative diabetic retinopathy (PDR), diagnosed by the standard method. The presence of peripheral abnormal lesions beyond the standard seven fields was examined. Results Ultrawide-field FA images demonstrated peripheral microaneurysms in six (54.5%) of 11 eyes with no DR and all eyes with moderate to severe NPDR and PDR. Peripheral retinal neovascularizations were detected in three (4.2%) of 71 eyes with NPDR and in 13 (36.1%) of 36 eyes with PDR. Peripheral vascular nonperfusion and vascular leakage were found in two-thirds of eyes with severe NPDR and PDR. Conclusions Ultrawide-field FA demonstrates peripheral lesions beyond standard fields, which can allow early detection and a close evaluation of DR. PMID:23204797

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

PubMed

Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

2014-03-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

Development of a Deep Learning Algorithm for Automatic Diagnosis of Diabetic Retinopathy.

PubMed

Raju, Manoj; Pagidimarri, Venkatesh; Barreto, Ryan; Kadam, Amrit; Kasivajjala, Vamsichandra; Aswath, Arun

2017-01-01

This paper mainly focuses on the deep learning application in classifying the stage of diabetic retinopathy and detecting the laterality of the eye using funduscopic images. Diabetic retinopathy is a chronic, progressive, sight-threatening disease of the retinal blood vessels. Ophthalmologists diagnose diabetic retinopathy through early funduscopic screening. Normally, there is a time delay in reporting and intervention, apart from the financial cost and risk of blindness associated with it. Using a convolutional neural network based approach for automatic diagnosis of diabetic retinopathy, we trained the prediction network on the publicly available Kaggle dataset. Approximately 35,000 images were used to train the network, which observed a sensitivity of 80.28% and a specificity of 92.29% on the validation dataset of ~53,000 images. Using 8,810 images, the network was trained for detecting the laterality of the eye and observed an accuracy of 93.28% on the validation set of 8,816 images.

P2X7 receptor antagonism: Implications in diabetic retinopathy.

PubMed

Platania, Chiara Bianca Maria; Giurdanella, Giovanni; Di Paola, Luisa; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio

2017-08-15

Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacological target in DR. Here we first carried out an in silico molecular modeling study in order to characterize the allosteric pocket in P2X7R, and identify a suitable P2X7R antagonist through molecular docking. JNJ47965567 was identified as the hit compound in docking calculations, as well as for its absorption, distribution, metabolism and excretion (ADME) profile. As an in vitro model of early diabetic retinopathy, human retinal pericytes were exposed to high glucose (25mM, 48h) that caused a significant (p<0.05) release of IL-1β and LDH. The block of P2X7R by JNJ47965567 significantly (p<0.05) reverted the damage elicited by high glucose, detected as IL-1β and LDH release. Overall, our findings suggest that the P2X7R represents an attractive pharmacological target to manage the early phase of diabetic retinopathy, and the compound JNJ47965567 is a good template to discover other P2X7R selective antagonists. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiation retinopathy: case report and review.

PubMed

Gupta, Abha; Dhawahir-Scala, Felipe; Smith, Amy; Young, Lorna; Charles, Steve

2007-04-05

Ocular damage from radiation treatment is a well established phenomenon. Many factors are now known to influence the incidence of radiation retinopathy, including total dosage and daily fraction size. Patients who are diabetic, hypertensive or received previous chemotherapy are more susceptible to radiation retinopathy. A 55 year old male was referred from the oncology department with epiphora. His medical history included Type 2 Insulin treated Diabetes Mellitus and hypertension. One year prior to presentation he had undergone a total rhinectomy with a 4 week course of post-operative radiotherapy for an aggressive sqaumous cell carcinoma of the nose. On examination the visual acuity was noted to be 6/36 left eye and 6/9 right eye. Posterior segment examination revealed marked retinal ischaemia present in the posterior pole and macular region of both eyes. The appearance was not thought to be typical of diabetic changes, radiation retinopathy being the more likely diagnosis especially in view of his history. Over the next four months the vision in both eyes rapidly deteriorated to 3/60 left eye and 1/60 right eye. Bilateral pan retinal photocoagulation was thought to be appropriate treatment at this point. This case highlights the importance for ophthalmologists and oncologists to be aware of the close relationship between diabetes and radiation treatment and the profound rapid impact this combination of factors may have on visual function. Radiation is being used with increasing frequency for ocular and orbital disease, because of this more cases of radiation retinopathy may become prevalent. Factors which may potentiate radiation retinopathy should be well known including, increased radiation dosage, increased fraction size, concomitant systemic vascular disease and use of chemotherapy. Counselling should be offered in all cases at risk of visual loss. As no effective treatment currently exists to restore visual function, monitoring of visual acuity in all cases

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

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.

Automated detection of dark and bright lesions in retinal images for early detection of diabetic retinopathy.

PubMed

Akram, Usman M; Khan, Shoab A

2012-10-01

There is an ever-increasing interest in the development of automatic medical diagnosis systems due to the advancement in computing technology and also to improve the service by medical community. The knowledge about health and disease is required for reliable and accurate medical diagnosis. Diabetic Retinopathy (DR) is one of the most common causes of blindness and it can be prevented if detected and treated early. DR has different signs and the most distinctive are microaneurysm and haemorrhage which are dark lesions and hard exudates and cotton wool spots which are bright lesions. Location and structure of blood vessels and optic disk play important role in accurate detection and classification of dark and bright lesions for early detection of DR. In this article, we propose a computer aided system for the early detection of DR. The article presents algorithms for retinal image preprocessing, blood vessel enhancement and segmentation and optic disk localization and detection which eventually lead to detection of different DR lesions using proposed hybrid fuzzy classifier. The developed methods are tested on four different publicly available databases. The presented methods are compared with recently published methods and the results show that presented methods outperform all others.

Frequency and Clinical Characteristics of Hydroxychloroquine Retinopathy in Korean Patients with Rheumatologic Diseases

PubMed Central

2017-01-01

This study aimed to evaluate the frequency and clinical characteristics of hydroxychloroquine (HCQ) retinopathy in Korean patients with rheumatologic diseases. We retrospectively reviewed medical records of 310 patients taking HCQ. Ophthalmic examinations included spectral-domain optical coherence tomography (SD-OCT), automated visual field test, and fundus autofluorescence. The severity of retinopathy was categorized as early, moderate, or severe, and the location was categorized as parafoveal, pericentral, or mixed pattern. Among 310 patients, 9 patients (2.9%) were diagnosed as HCQ retinopathy. Among the patients with HCQ use ≥ 5 years (n = 174), the frequency was 5.2%. Only 1 (11.1%) of the 9 patients was symptomatic. The mean daily dose per kilogram of real body weight of the 9 patients was 5.6 mg, and only 3 had used 6.5 mg or more. Four of the 9 patients had severe HCQ retinopathy. Six of the 9 patients showed pericentral or mixed pattern of retinal damage. Consequently, the frequency of HCQ retinopathy in Korean patients was not low, especially when administered at a high cumulative dose and for a long duration. Screening of HCQ retinopathy by the recommended guidelines that include SD-OCT seems useful and should be done to detect retinal damage earlier in patients with chronic exposure to HCQ. PMID:28145658

Frequency and Clinical Characteristics of Hydroxychloroquine Retinopathy in Korean Patients with Rheumatologic Diseases.

PubMed

Eo, Doo Ri; Lee, Min Gyu; Ham, Don Il; Kang, Se Woong; Lee, Jaejoon; Cha, Hoon Suk; Koh, Eunmi; Kim, Sang Jin

2017-03-01

This study aimed to evaluate the frequency and clinical characteristics of hydroxychloroquine (HCQ) retinopathy in Korean patients with rheumatologic diseases. We retrospectively reviewed medical records of 310 patients taking HCQ. Ophthalmic examinations included spectral-domain optical coherence tomography (SD-OCT), automated visual field test, and fundus autofluorescence. The severity of retinopathy was categorized as early, moderate, or severe, and the location was categorized as parafoveal, pericentral, or mixed pattern. Among 310 patients, 9 patients (2.9%) were diagnosed as HCQ retinopathy. Among the patients with HCQ use ≥ 5 years (n = 174), the frequency was 5.2%. Only 1 (11.1%) of the 9 patients was symptomatic. The mean daily dose per kilogram of real body weight of the 9 patients was 5.6 mg, and only 3 had used 6.5 mg or more. Four of the 9 patients had severe HCQ retinopathy. Six of the 9 patients showed pericentral or mixed pattern of retinal damage. Consequently, the frequency of HCQ retinopathy in Korean patients was not low, especially when administered at a high cumulative dose and for a long duration. Screening of HCQ retinopathy by the recommended guidelines that include SD-OCT seems useful and should be done to detect retinal damage earlier in patients with chronic exposure to HCQ.

[Crystalline retinopathy].

PubMed

Rasquin, F

2007-01-01

Crystalline retinopathy is characterized by intraretinal crystalline deposits that, according to their etiology, can be localized in the macular area or, indeed, be found in the entire retina. These deposits can be associated or not to visual loss and electrophysiological perturbations. Among the toxic drugs leading to this retinopathy are tamoxifen, canthaxanthine, methoxyflurane, talc and nitrofurantoin. A detailed description of tamoxifen and canthaxanthine toxicity is reported in this chapter.

Preventing radiation retinopathy with hyperfractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monroe, Alan T.; Bhandare, Niranjan; Morris, Christopher G.

2005-03-01

Purpose: The purpose of this study was to determine factors associated with the development of radiation retinopathy in a large series of patients with head-and-neck cancer. In particular, we addressed whether the use of hyperfractionated radiation therapy was effective in reducing the risk of retinopathy. Methods and materials: One hundred eighty-six patients received a significant dose to the retina as part of curative radiotherapy. Primary sites included: nasopharynx, 46; paranasal sinus, 64; nasal cavity, 69; and palate, 7. Prescription doses varied depending on primary site and histology. Hyperfractionated (twice-daily) radiation was delivered to 42% of the patients in this study,more » typically at 1.10 to 1.20 Gy per fraction. The remainder were treated once-daily. Retinal doses were determined from computerized dosimetry plans when available. For all other patients, retinal doses were retrospectively calculated using reconstructed off-axis dosimetry taken from contours through the center of the globes. Retinal dose was defined as the minimum dose received by at least 25% of the globe. The median retinal dose was 56.85 Gy. Patients were followed for a median of 7.6 years. Results: Thirty-one eyes in 30 patients developed radiation retinopathy, resulting in monocular blindness in 25, bilateral blindness in 1, and decreased visual acuity in 4. The median time to the diagnosis of retinopathy was 2.6 years (range, 11 months to 5.3 years). The actuarial incidence of developing radiation retinopathy was 20% at both 5 and 10 years. The incidence of developing ipsilateral blindness due to retinopathy was 16% at 5 years and 17% at 10 years. Site-specific incidences varied considerably, with ethmoid sinus (9 of 25, 36%), nasal cavity (13 of 69, 19%), and maxillary sinus (6 of 35, 17%) being the most common sites associated with radiation retinopathy. Three of 72 patients (4%) receiving retinal doses less than 50 Gy developed retinopathy. Higher retinal doses

Evolving Oxygen Landscape of the Early Atmosphere and Oceans

NASA Astrophysics Data System (ADS)

Lyons, T. W.; Reinhard, C. T.; Planavsky, N. J.

2013-12-01

The past decade has witnessed remarkable advances in our understanding of oxygen on the early Earth, and a new framework, the topic of this presentation, is now in place to address the controls on spatiotemporal distributions of oxygen and their potential relationships to deep-Earth processes. Recent challenges to the Archean biomarker record have put an added burden on inorganic geochemistry to fingerprint and quantify the early production, accumulation, and variation of biospheric oxygen. Fortunately, a wide variety of techniques now point convincingly to photosynthetic oxygen production and dynamic accumulation well before the canonical Great Oxidation Event (GOE). Recent modeling of sulfur recycling over this interval allows for transient oxygen accumulation in the atmosphere without the disappearance of non-mass-dependent (NMD) sulfur isotope anomalies from the stratigraphic record and further allows for persistent accumulation in the atmosphere well before the permanent disappearance of NMD signals. This recent work suggests that the initial rise of oxygen may have occurred in fits and starts rather than a single step, and that once permanently present in the atmosphere, oxygen likely rose to high levels and then plummeted, in phase with the Paleoproterozoic Lomagundi positive carbon isotope excursion. More than a billion years of oxygen-free conditions in the deep ocean followed and set a challenging course for life, including limited abundances and diversity of eukaryotic organisms. Despite this widespread anoxia, sulfidic (euxinic) conditions were likely limited to productive ocean margins. Nevertheless, euxinia was sufficiently widespread to impact redox-dependent nutrient relationships, particularly the availability of bioessential trace metals critical in the nitrogen cycle, which spawned feedbacks that likely maintained oxygen at very low levels in the ocean and atmosphere and delayed the arrival of animals. Then, in the mid, pre-glacial Neoproterozoic

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

Grating visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty; Good, William V

2011-07-01

To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

PubMed

Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

2012-03-01

The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

Retinopathy of Prematurity

ERIC Educational Resources Information Center

Steinweg, Sue Byrd; Griffin, Harold C.; Griffin, Linda W.; Gingras, Happy

2005-01-01

The eyes of premature infants are especially vulnerable to injury after birth. A serious complication is called retinopathy of prematurity (ROP), which is abnormal growth of the blood vessels in an infant's eye. Retinopathy of prematurity develops when abnormal blood vessels grow and spread throughout the retina, which is the nerve tissue at the…

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells

PubMed Central

Monetti, Emanuela; Kadono, Takashi; Bouteau, François

2014-01-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca2+ concentration ([Ca2+]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·–) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·– generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca2+]cyt increase and singlet oxygen production, do not seem to be involved in PCD. PMID:24420571

Metabolic Prosthesis for Oxygenation of Ischemic Tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenbaum, Elias

2009-01-01

This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer,more » suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.« less

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.

Retinal vascular speed <0.5 disc diameter per week as an early sign of retinopathy of prematurity requiring treatment.

PubMed

Solans Pérez de Larraya, Ana M; Ortega Molina, José M; Fernández, José Uberos; Escudero Gómez, Júlia; Salgado Miranda, Andrés D; Chaves Samaniego, Maria J; García Serrano, José L

2018-03-01

To analyse the speed of temporal retinal vascularisation in preterm infants included in the screening programme for retinopathy of prematurity. A total of 185 premature infants were studied retrospectively between 2000 and 2017 in San Cecilio University Hospital of Granada, Spain. The method of binocular indirect ophthalmoscopy with indentation was used for the examination. The horizontal disc diameter was used as a unit of length. Speed of temporal retinal vascularisation (disc diameter/week) was calculated as the ratio between the extent of temporal retinal vascularisation (disc diameter) and the time in weeks. The weekly temporal retinal vascularisation (0-1.25 disc diameter/week, confidence interval) was significantly higher in no retinopathy of prematurity (0.73 ± 0.22 disc diameter/week) than in stage 1 retinopathy of prematurity (0.58 ± 0.22 disc diameter/week). It was also higher in stage 1 than in stages 2 (0.46 ± 0.14 disc diameter/week) and 3 of retinopathy of prematurity (0.36 ± 0.18 disc diameter/week). The rate of temporal retinal vascularisation (disc diameter/week) decreases when retinopathy of prematurity stage increases. The area under the receiver operating characteristic curve was 0.85 (95% confidence interval: 0.79-0.91) for retinopathy of prematurity requiring treatment versus not requiring treatment. The best discriminative cut-off point was a speed of retinal vascularisation <0.5 disc diameter/week, with a sensitivity and a specificity of 84.8% and 77%, respectively. The rate of temporal retinal vascularisation is a quantifiable observation that can help to alert a clinician that treatment of retinopathy of prematurity may be required. However, before becoming a new standard of care for treatment, it requires careful documentation, with agreement between several ophthalmologists.

Oxygen induces mutation in a strict anaerobe, Prevotella melaninogenica.

PubMed

Takumi, Shota; Komatsu, Masaharu; Aoyama, Kohji; Watanabe, Kunitomo; Takeuchi, Toru

2008-05-15

Strict anaerobes are highly sensitive to oxygen, but the mutagenicity of oxygen in strict anaerobes has not been well understood. Prevotella melaninogenica, a strict anaerobe, is susceptible to oxygen and shows an increase in oxidative DNA damage upon exposure to oxygen. In this study, we have investigated the mutagenicity of oxygen and the types of mutations induced by oxygen. Exposure to oxygen decreased cell survival and increased the levels of 8-oxo-deoxyguanosine (8-oxodG). The frequency of rifampicin-resistant mutants was markedly increased after exposure to oxygen. After sequencing a 254-bp fragment of the rpoB gene, which encodes the beta subunit of bacterial RNA polymerase, a target molecule of rifampicin, we found that most mutants induced by oxygen had GC to TA transversions, a signature of 8-oxodG. In addition, all detected single-nucleotide changes would lead to amino acid changes that confer rifampicin resistance. These results indicate that oxygen is mutagenic in a strict anaerobe, P. melaninogenica, and its mutagenic characteristics could be analyzed with this experimental system.

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

PubMed Central

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

2013-01-01

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

The Use of Optical Coherence Tomography for the Detection of Early Diabetic Retinopathy.

PubMed

Somfai, Gabor Mark; Gerding, Heinrich; DeBuc, Delia Cabrera

2018-04-01

Diabetic retinopathy (DR) is one of the leading causes of vision loss globally with a severe burden on all societies due to its high treatment and rehabilitation costs. The early diagnosis of DR may provide preventive steps (including retinal laser therapy and tight carbohydrate, blood pressure, and cholesterol control) that could in turn help to avoid progression of the pathology with the resultant vision loss. Optical coherence tomography (OCT) enables the in vivo structural imaging of the retina, providing both qualitative (structure) and quantitative (thickness) information. In the past decades, extensive OCT research has been done in the field of DR. In the present review, we are focusing on those that were aiming at detection of the earliest retinal changes before DR could be diagnosed funduscopically. The latest, widely available technology of spectral-domain (SD-)OCT comes with a fast and reliable retinal imaging, which, together with the most recent developments in image processing and artificial intelligence, holds the promise of developing a quick and efficient, state-of-the-art screening tool for DR. Georg Thieme Verlag KG Stuttgart · New York.

Reactive Oxygen Species on the Early Earth and Survival of Bacteria

NASA Technical Reports Server (NTRS)

Balk, Melikea; Mason, Paul; Stams, Alfons J. M.; Smidt, Hauke; Freund, Friedemann; Rothschild, Lynn

2011-01-01

An oxygen-rich atmosphere appears to have been a prerequisite for complex, multicellular life to evolve on Earth and possibly elsewhere in the Universe. However it remains unclear how free oxygen first became available on the early Earth. A potentially important, and as yet poorly constrained pathway, is the production of oxygen through the weathering of rocks and release into the near-surface environment. Reactive Oxygen Species (ROS), as precursors to molecular oxygen, are a key step in this process, and may have had a decisive impact on the evolution of life, present and past. ROS are generated from minerals in igneous rocks during hydrolysis of peroxy defects, which consist of pairs of oxygen anions oxidized to the valence state -1 and during (bio) transformations of iron sulphide minerals. ROS are produced and consumed by intracellular and extracellular reactions of Fe, Mn, C, N, and S species. We propose that, despite an overall reducing or neutral oxidation state of the macroenvironment and the absence of free O2 in the atmosphere, organisms on the early Earth had to cope with ROS in their microenvironments. They were thus under evolutionary pressure to develop enzymatic and other defences against the potentially dangerous, even lethal effects of oxygen and its derived ROS. Conversely it appears that microorganisms learned to take advantage of the enormous reactive potential and energy gain provided by nascent oxygen. We investigate how oxygen might be released through weathering. We test microorganisms in contact with rock surfaces and iron sulphides. We model bacteria such as Deionococcus radiodurans and Desulfotomaculum, Moorella and Bacillus species for their ability to grow or survive in the presence of ROS. We examine how early Life might have adapted to oxygen.

Treatment of radiation-induced cystitis with hyperbaric oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, J.P.; Boland, F.P.; Mori, H.

The effects of hyperbaric oxygen on radiation cystitis have been documented in 3 patients with radiation-induced hemorrhagic cystitis refractory to conventional therapy. Cessation of gross hematuria and reversal of cystoscopic bladder changes were seen in response to a series of hyperbaric oxygen treatments of 2 atmosphere absolute pressure for 2 hours. To our knowledge this is the first report of cystoscopically documented healing of radiation-induced bladder injury.

Aggressive posterior retinopathy of prematurity in large preterm babies in South India.

PubMed

Shah, Parag K; Narendran, Venkatapathy; Kalpana, Narendran

2012-09-01

To describe aggressive posterior retinopathy of prematurity (APROP) in a subset of premature babies, having gestational age (GA) of ≥28 weeks and birth weight (BW) of ≥1000 g. Retrospective observational case series. Case records of 99 babies, who were diagnosed to have APROP between July 2002 and October 2010 were reviewed. Fundus fluorescein angiography (FFA) was carried out in 19 babies. The mean GA was 31.7 weeks (range 28-35 weeks) and mean BW was 1572 g (range 1000-2310 g). All these babies received supplemental unblended oxygen 3 days or longer after birth. Of the 52 babies who had an eye exam in the neonatal intensive care unit prior to discharge, 35 babies had loss of vascularised retina from zone II to zone I and four babies from zone III to zone I, when examined as an outpatient. FFA revealed large geographic areas of vaso-obliteration (more than 30 disc areas) posterior to the shunt vessels within vascularised retina. Features of severe capillary bed loss in the vascularised retina were seen in our cases. Oxygen could be a precipitating factor in causing this retinopathy of prematurity in large babies.

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)

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.

Automated microaneurysm detection in diabetic retinopathy using curvelet transform.

PubMed

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

2016-10-01

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

Enhancement of scutellarin oral delivery efficacy by vitamin B12-modified amphiphilic chitosan derivatives to treat type II diabetes induced-retinopathy.

PubMed

Wang, Jingnan; Tan, Jiayun; Luo, Jiahao; Huang, Peilin; Zhou, Wuyi; Chen, Luming; Long, Lingli; Zhang, Li-Ming; Zhu, Banghao; Yang, Liqun; Deng, David Y B

2017-03-01

neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.

Automated detection of photoreceptor disruption in mild diabetic retinopathy on volumetric optical coherence tomography

PubMed Central

Wang, Zhuo; Camino, Acner; Zhang, Miao; Wang, Jie; Hwang, Thomas S.; Wilson, David J.; Huang, David; Li, Dengwang; Jia, Yali

2017-01-01

Diabetic retinopathy is a pathology where microvascular circulation abnormalities ultimately result in photoreceptor disruption and, consequently, permanent loss of vision. Here, we developed a method that automatically detects photoreceptor disruption in mild diabetic retinopathy by mapping ellipsoid zone reflectance abnormalities from en face optical coherence tomography images. The algorithm uses a fuzzy c-means scheme with a redefined membership function to assign a defect severity level on each pixel and generate a probability map of defect category affiliation. A novel scheme of unsupervised clustering optimization allows accurate detection of the affected area. The achieved accuracy, sensitivity and specificity were about 90% on a population of thirteen diseased subjects. This method shows potential for accurate and fast detection of early biomarkers in diabetic retinopathy evolution. PMID:29296475

Automated detection of photoreceptor disruption in mild diabetic retinopathy on volumetric optical coherence tomography.

PubMed

Wang, Zhuo; Camino, Acner; Zhang, Miao; Wang, Jie; Hwang, Thomas S; Wilson, David J; Huang, David; Li, Dengwang; Jia, Yali

2017-12-01

Diabetic retinopathy is a pathology where microvascular circulation abnormalities ultimately result in photoreceptor disruption and, consequently, permanent loss of vision. Here, we developed a method that automatically detects photoreceptor disruption in mild diabetic retinopathy by mapping ellipsoid zone reflectance abnormalities from en face optical coherence tomography images. The algorithm uses a fuzzy c-means scheme with a redefined membership function to assign a defect severity level on each pixel and generate a probability map of defect category affiliation. A novel scheme of unsupervised clustering optimization allows accurate detection of the affected area. The achieved accuracy, sensitivity and specificity were about 90% on a population of thirteen diseased subjects. This method shows potential for accurate and fast detection of early biomarkers in diabetic retinopathy evolution.

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

PubMed Central

2014-01-01

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

[Treatment with human recombinant erythropoietin and frequency of retinopathy of prematurity].

PubMed

Rudzińska, Iwona M; Kornacka, Maria K; Pawluch, Robert

2002-01-01

The aim of our study was to assess frequency of ROP in VLBW and ELBW treated with rhEPO in preventing anemia. In 36 newborns with birth weight 480 to 1490 g (median 1032 g) and 24 to 32 weeks of gestational age (median 28.0 weeks) we have estimated concentration of cord erythropoietin. According this concentration we have divided our material into two groups. In first group of 22 newborns with cord concentration of EPO < 10 mU/ml we started early erythropoietin (rhEPO) therapy which was continued by 6 weeks. Second group of 14 no early usage newborns had cord EPO concentration > 10 mU/ml. In second group the control level of serum EPO was measured in 15th day of life. In newborns from second group in which the EPO concentration during two weeks decreased below 10 mU/ml we started to use rhEPO as a late usage. First oculistic consultation took place in the 5th week of life according to the screening performed in our country. In the first group (n = 22) with early EPO treatment retinopathy was recognized in 15 preterm newborns (68.2%). Eight of them (53.3%) had advanced form of retinopathy ROP (III lub III+) and were undergone a laserotherapy. In the group of late usage of rhEPO (n = 14) 8 newborns (57.1%) had signs of retinopathy, but only 3 of them (37.5%) required laserotherapy because of advanced form of ROP (III lub III+).

Correlational Study of Diabetic Retinopathy and Hearing Loss.

PubMed

Ooley, Caroline; Jun, Weon; Le, Kim; Kim, Allen; Rock, Nathan; Cardenal, Molly; Kline, Rebecca; Aldrich, Drew; Hayes, John

2017-03-01

Our research goal was to complete a retrospective chart review to determine if there is a correlation between the level of diabetic retinopathy and diabetic neurosensory hearing loss. A retrospective analysis of 175 Department of Veterans Affairs Computerized Patient Record System charts was completed at the VA Portland Health Care System. Subjects were classified by degree of diabetic retinopathy as follows: no diabetic retinopathy (n = 80), mild nonproliferative diabetic retinopathy (n = 51), moderate nonproliferative diabetic retinopathy (n = 25), and combined severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (PDR) (n = 17). Degree of sensorineural hearing was collected for each ear. Additionally, measures of diabetic control, including hemoglobin A1C, and creatinine, were recorded. After controlling for diabetic control, as measured by HbA1C and creatinine, level of diabetic retinopathy was significantly associated with hearing loss severity in both ears (right ear, P = .018 and left ear, P = .007). When adjusted to include diabetes control, the severity of diabetic retinopathy showed a correlation with degree of hearing loss at most levels. Because of this association, recommendation for hearing evaluations may be considered for those with mild, moderate, or severe nonproliferative or proliferative diabetic retinopathy.

Role of agonistic autoantibodies against type-1 angiotensin II receptor in the pathogenesis of retinopathy in preeclampsia.

PubMed

Liu, Fang; Wang, Yuxian; Wang, Xiaofang; Zheng, Yanqian; Jin, Zhu; Zhi, Jianming

2016-07-06

To investigate the mechanism underlying AT1-AA-induced retinopathy in severe preeclampsia by measuring the positive rate and titer of AT1-AA in plasma from women with severe preeclampsia and normal pregnant women to see whether AT1-AA titer was correlated with the grade of retinopathy. A preeclampsia rat model was also established by intravenous injection of AT1-AA extracted from the plasma of patient suffering from severe preeclampsia. The results showed that the plasma titer and positive rate of AT1-AA were significantly higher in women with severe preeclampsia than normal pregnant women. The antibody titer in cases of severe preeclampsia was associated with the grade of retinopathy, and positively correlated with the level of TNF-α and VEGF. The animal experiment results showed that the modeled rats presented symptoms very similar to symptoms of human preeclampsia, including retinopathy. Ocular fundus examination showed retinal microvascular abnormalities, hemorrhaging and leakage in the severe preeclampsia. Morphological changes included edema, thickening of the INL and ONL, and pigment atrophy. TNF-α and VEGF levels were increased in the vitreous humor and retina of the model rats. Our studies results suggest that abnormal expression of AT1-AA could induce damage to retinal capillary endothelial cells and increase vascular permeability, resulting in retinopathy.

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.

Malarial Retinopathy in Bangladeshi Adults

PubMed Central

Sayeed, Abdullah Abu; Maude, Richard J.; Hasan, Mahtab Uddin; Mohammed, Noor; Hoque, M. Gofranul; Dondorp, Arjen M.; Faiz, M. Abul

2011-01-01

To establish if assessment of malarial retinopathy in adult malaria using ophthalmoscopy by non-ophthalmologists has clinical and prognostic significance, 210 Bangladeshi adults were assessed by both direct and indirect ophthalmoscopy; 20 of 20 healthy subjects and 20 of 20 patients with vivax malaria showed no retinal changes, whereas in patients with falciparum malaria, indirect ophthalmoscopy revealed malarial retinopathy (predominantly retinal hemorrhages) in 18 of 21 (86%) fatal, 31 of 75 (41%) cerebral, 16 of 64 (25%) non-cerebral but severe, and 1 of 31 (3%) uncomplicated cases. Direct ophthalmoscopy missed retinopathy in one of these cases and found fewer retinal hemorrhages (mean difference = 3.09; 95% confidence interval = 1.50–4.68; P < 0.0001). Severity of retinopathy increased with severity of disease (P for trend < 0.0001), and renal failure, acidosis, and moderate/severe retinopathy were independent predictors of mortality by both ophthalmoscopic techniques. Direct ophthalmoscopy by non-ophthalmologists is an important clinical tool to aid diagnosis and prognosis in adults with severe malaria, and indirect ophthalmoscopy by non-ophthalmologists, although more sensitive, provides minimal additional prognostic information. PMID:21212217

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

PubMed

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

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). 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. 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, r 2 =0.1043, P ≤0.0001; rs3025021 vs rs2010963: D'=0.442, r 2 =0.0446, P =0.149; rs3025035 vs rs2010963: D'=0.505, r 2 =0.0214, P =0.142. 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 different populations

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

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

[Effects of propranolol on oxygen-induced retinal neovascularization in mouse].

PubMed

Huang, Xuerong; Wang, Yajuan; Yang, Guangran; Yang, Zixin; Zhang, Jingshang

2016-02-01

To investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR). Thirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 ± 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg·time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM). Compared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 ± 9.9)% and (5.6 ± 2.3)% vs. (16.2 ± 10.0)% and (2.2 ± 0.8)%, (25.9 ± 5.0)% and (2.1 ± 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 ± 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 ± 8.9) per slide and the propranolol IP injection group (18.0 ± 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 ± 8.1) per

Hydroxychloroquine retinopathy.

PubMed

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

2017-06-01

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.

Hydroxychloroquine retinopathy

PubMed Central

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

2017-01-01

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. PMID:28282061

Effects of medical therapies on retinopathy progression in type 2 diabetes.

PubMed

Chew, Emily Y; Ambrosius, Walter T; Davis, Matthew D; Danis, Ronald P; Gangaputra, Sapna; Greven, Craig M; Hubbard, Larry; Esser, Barbara A; Lovato, James F; Perdue, Letitia H; Goff, David C; Cushman, William C; Ginsberg, Henry N; Elam, Marshall B; Genuth, Saul; Gerstein, Hertzel C; Schubart, Ulrich; Fine, Lawrence J

2010-07-15

We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; Clinical

Ebselen by modulating oxidative stress improves hypoxia-induced macroglial Müller cell and vascular injury in the retina.

PubMed

Tan, Sih Min; Deliyanti, Devy; Figgett, William A; Talia, Dean M; de Haan, Judy B; Wilkinson-Berka, Jennifer L

2015-07-01

Oxidative stress is an important contributor to glial and vascular cell damage in ischemic retinopathies. We hypothesized that ebselen via its ability to reduce reactive oxygen species (ROS) and augment nuclear factor-like 2 (Nrf2) anti-oxidants would attenuate hypoxia-induced damage to macroglial Müller cells and also lessen retinal vasculopathy. Primary cultures of rat Müller cells were exposed to normoxia (21% O2), hypoxia (0.5% O2) and ebselen (2.5 μM) for up to 72 h. Oxygen-induced retinopathy (OIR) was induced in C57BL/6J mice while control mice were housed in room air. Mice received vehicle (saline, 5% dimethyl sulfoxide) or ebselen (10 mg/kg) each day between postnatal days 6-18. In cultured Müller cells, flow cytometry for dihydroethidium revealed that ebselen reduced the hypoxia-induced increase in ROS levels, whilst increasing the expression of Nrf2-regulated anti-oxidant genes, heme oxygenase 1, glutathione peroxidase-1, NAD(P)H dehydrogenase quinone oxidoreductase 1 and glutamate-cysteine ligase. Moreover, in Müller cells, ebselen reduced the hypoxia-induced increase in protein levels of pro-angiogenic and pro-inflammatory factors including vascular endothelial growth factor, interleukin-6, monocyte chemoattractant-protein 1 and intercellular adhesion molecule-1, and the mRNA levels of glial fibrillary acidic protein (GFAP), a marker of Müller cell injury. Ebselen improved OIR by attenuating capillary vaso-obliteration and neovascularization and a concomitant reduction in Müller cell gliosis and GFAP. We conclude that ebselen protects against hypoxia-induced injury of retinal Müller cells and the microvasculature, which is linked to its ability to reduce oxidative stress, vascular damaging factors and inflammation. Agents such as ebselen may be potential treatments for retinopathies that feature oxidative stress-mediated damage to glia and the microvasculature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Retinal microaneurysm count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme.

PubMed

Sjølie, A K; Klein, R; Porta, M; Orchard, T; Fuller, J; Parving, H H; Bilous, R; Aldington, S; Chaturvedi, N

2011-03-01

To study the association between baseline retinal microaneurysm score and progression and regression of diabetic retinopathy, and response to treatment with candesartan in people with diabetes. This was a multicenter randomized clinical trial. The progression analysis included 893 patients with Type 1 diabetes and 526 patients with Type 2 diabetes with retinal microaneurysms only at baseline. For regression, 438 with Type 1 and 216 with Type 2 diabetes qualified. Microaneurysms were scored from yearly retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Retinopathy progression and regression was defined as two or more step change on the ETDRS scale from baseline. Patients were normoalbuminuric, and normotensive with Type 1 and Type 2 diabetes or treated hypertensive with Type 2 diabetes. They were randomized to treatment with candesartan 32 mg daily or placebo and followed for 4.6 years. A higher microaneurysm score at baseline predicted an increased risk of retinopathy progression (HR per microaneurysm score 1.08, P < 0.0001 in Type 1 diabetes; HR 1.07, P = 0.0174 in Type 2 diabetes) and reduced the likelihood of regression (HR 0.79, P < 0.0001 in Type 1 diabetes; HR 0.85, P = 0.0009 in Type 2 diabetes), all adjusted for baseline variables and treatment. Candesartan reduced the risk of microaneurysm score progression. Microaneurysm counts are important prognostic indicators for worsening of retinopathy, thus microaneurysms are not benign. Treatment with renin-angiotensin system inhibitors is effective in the early stages and may improve mild diabetic retinopathy. Microaneurysm scores may be useful surrogate endpoints in clinical trials. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rinaldo, J.E.; English, D.; Levine, J.

1988-02-01

Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria.more » However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.« less

Oxygenation history of the Neoproterozoic to early Phanerozoic and the rise of land plants

NASA Astrophysics Data System (ADS)

Wallace, Malcolm W.; Hood, Ashleigh vS.; Shuster, Alice; Greig, Alan; Planavsky, Noah J.; Reed, Christopher P.

2017-05-01

There has been extensive debate about the history of Earth's oxygenation and the role that land plant evolution played in shaping Earth's ocean-atmosphere system. Here we use the rare earth element patterns in marine carbonates to monitor the structure of the marine redox landscape through the rise and diversification of animals and early land plants. In particular, we use the relative abundance of cerium (Ceanom), the only redox-sensitive rare earth element, in well-preserved marine cements and other marine precipitates to track seawater oxygen levels. Our results indicate that there was only a moderate increase in oceanic oxygenation during the Ediacaran (average Cryogenian Ceanom = 1.1, average Ediacaran Ceanom = 0.62), followed by a decrease in oxygen levels during the early Cambrian (average Cryogenian Ceanom = 0.90), with significant ocean anoxia persisting through the early and mid Paleozoic (average Early Cambrian-Early Devonian Ceanom = 0.84). It was not until the Late Devonian that oxygenation levels are comparable to the modern (average of all post-middle Devonian Ceanom = 0.55). Therefore, this work confirms growing evidence that the oxygenation of the Earth was neither unidirectional nor a simple two-stage process. Further, we provide evidence that it was not until the Late Devonian, when large land plants and forests first evolved, that oxygen levels reached those comparable to the modern world. This is recorded with the first modern-like negative Ceanom (values <0.6) occurring at around 380 Ma (Frasnian). This suggests that land plants, rather than animals, are the 'engineers' responsible for the modern fully oxygenated Earth system.

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 (Pretinopathy, to prevent the problem in type I diabetes and to treat the early stages in type II diabetes.

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Hyperbaric oxygen: Primary treatment of radiation-induced hemorrhagic cystitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, J.P.; Neville, E.C.

Of 8 patients with symptoms of advanced cystitis due to pelvic radiation treated with hyperbaric oxygen 7 are persistently improved during followup. All 6 patients treated for gross hematuria requiring hospitalization have been free of symptoms for an average of 24 months (range 6 to 43 months). One patient treated for stress incontinence currently is dry despite little change in bladder capacity, implying salutary effect from hyperbaric oxygen on the sphincter mechanism. One patient with radiation-induced prostatitis failed to respond. This experience suggests that hyperbaric oxygen should be considered the primary treatment for patients with symptomatic radiation-induced hemorrhagic cystitis.

Can We Stop the Current Epidemic of Blindness From Retinopathy of Prematurity?

PubMed

Dutta, Sourabh; Raghuveer, Talkad; Vinekar, Anand; Dogra, Mangat Ram

2016-11-07

Retinopathy of Prematurity (ROP) is a retinal vascular disease of the premature infant. There have been significant advances in the understanding of the pathogenesis, prevention, detection and treatment of severe ROP. In developed countries, all premature infants at risk for ROP are screened routinely based on national guidelines and treatment is prompt, resulting in good visual outcomes. Blindness from ROP is a rare event in these countries. However, there is an ongoing epidemic of ROP- induced blindness in India. The reasons for this epidemic of ROP blindness are many and include increasing survival of premature infants, lack of equipment such as oxygen-blenders and pulse oximeters that are necessary for safe use of supplemental oxygen in premature infants, lack of routine screening for ROP, lack of trained personnel for ROP screening, and lack of Ophthalmologists to promptly initiate treatment when infants develop severe ROP. All the identified causes can be resolved with a concerted national co-operative effort of Pediatricians, Neonatologists, Ophthalmologists, Indian Academy of Pediatrics, National Neonatology Forum, Indian Academy of Ophthalmologists, Government of India, and parents of premature infants. We feel that tt is possible to stop the current epidemic of preventable childhood blindness from ROP with concerted action by all stakeholders.

Sickle cell retinopathy: A literature review.

PubMed

Ribeiro, Marina Viegas Moura Rezende; Jucá, João Vitor de Omena; Alves, Anna Luyza Correia Dos Santos; Ferreira, Caio Victor Oliveira; Barbosa, Fabiano Timbó; Ribeiro, Êurica Adélia Nogueira

2017-12-01

Hemoglobinopathies are a group of hereditary diseases that cause quantitative or qualitative changes in the shape, function or synthesis of hemoglobin. One of the most common is sickle cell anemia, which, due to sickling of erythrocytes, causes vaso-occlusive phenomena. Among the possible ocular manifestations, the most representative is retinopathy, which can lead to blindness if left untreated. Therefore, periodic ophthalmologic monitoring of these patients is important for early diagnosis and adequate therapeutic management, which can be done localy by treating the lesions in the eyes, or systemically.

Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea.

PubMed

de Sisternes, Luis; Hu, Julia; Rubin, Daniel L; Marmor, Michael F

2015-05-01

To evaluate the relative involvement of inner and outer retina in hydroxychloroquine (HCQ) retinopathy while on the drug, and after drug cessation, using data from spectral-domain optical coherence tomography (SD-OCT). A total of 102 SD-OCT scans were obtained from 11 patients (classified as having early, moderate, or severe stages of toxicity) over a period of 4 years after cessation of HCQ. The inner and outer retina boundaries were identified automatically to measure thickness and characterize progression topographically. The segmentation of retinal layers was verified in SD-OCT cross-sections for all eyes and scans included in this study (a total of 102 scans). Topographic analysis showed that inner retina was not involved in HCQ toxicity to any meaningful degree, either between stages of retinopathy or after the drug is stopped. The characteristic bull's eye pattern of outer macula thinning appears when comparing moderate retinopathy (before any RPE damage) to the early stage. Later damage, as toxicity evolved to a severe stage, was diffuse across most of the macula. If the drug was stopped at an early or moderate stage, progression was limited to the first year and occurred diffusely without parafoveal localization. Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.

Prion protein is essential for diabetic retinopathy-associated neovascularization.

PubMed

Zhu, Lingyan; Xu, Jixiong; Liu, Ying; Gong, Tian; Liu, Jianying; Huang, Qiong; Fischbach, Shane; Zou, Wenquan; Xiao, Xiangwei

2018-05-30

Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrP c ) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrP c is associated with physiological and pathological vascularization. Nevertheless, a role for PrP c in the development of DR has not been appreciated. Here, we addressed this question. We found that the development of streptozocin (STZ)-induced DR, but not the STZ-induced hyperglycemia/diabetes itself, was significantly attenuated in PrP c -KO mice, compared to control wildtype (WT) mice, evident by measurement of retinal vascular leakage, retinal neovascularization, a retinopathy score and visual acuity assessment. Moreover, the attenuation of DR severity seemingly resulted from attenuation of retinal neovascularization via VEGF/ras/rac signaling. Together, our study suggests a previously unappreciated role for PrP c in the development of DR.

Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

PubMed

Cayabyab, Rowena; Ramanathan, Rangasamy

2016-01-01

Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent

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

Diabetic retinopathy screening: global and local perspective.

PubMed

Gangwani, R A; Lian, J X; McGhee, S M; Wong, D; Li, K Kw

2016-10-01

Diabetes mellitus has become a global epidemic. It causes significant macrovascular complications such as coronary artery disease, peripheral artery disease, and stroke; as well as microvascular complications such as retinopathy, nephropathy, and neuropathy. Diabetic retinopathy is known to be the leading cause of blindness in the working-age population and may be asymptomatic until vision loss occurs. Screening for diabetic retinopathy has been shown to reduce blindness by timely detection and effective laser treatment. Diabetic retinopathy screening is being done worldwide either as a national screening programme or hospital-based project or as a community-based screening programme. In this article, we review different methods of screening including grading used to detect the severity of sight-threatening retinopathy and the newer screening methods. This review also includes the method of systematic screening being carried out in Hong Kong, a system that has helped to identify diabetic retinopathy among all attendees in public primary care clinics using a Hong Kong-wide public patients' database.

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

Purtscher-like retinopathy associated with squamous cell carcinoma of the cervix.

PubMed

Ting, Darren Shu Jeng; Smith, Jonathan; Talks, Stephen James

2018-02-01

To describe a previously unreported case of Purtscher-like retinopathy secondary to severe acute renal failure associated with squamous cell carcinoma of the cervix. This is a case report. A 31-year-old female presented with a week history of acute abdominal pain, vomiting and severe renal failure followed by a sudden onset of bilateral visual loss. Vision was hand movement in either eye with central scotoma. Ophthalmic examination demonstrated bilateral retinal thickening and whitening with intraretinal hemorrhages localized to the peripapillary area, consistent with the diagnosis of Purtscher-like retinopathy. Further systemic examination revealed bilateral hydronephrosis secondary to underlying undiagnosed cervical carcinoma. Patient was treated with a short course of high-dose steroids. At 2 months, patient vision remained poor despite the resolution of retinal edema and hemorrhages. This case serves as the first report of Purtscher-like retinopathy secondary to acute renal failure associated with cervical carcinoma, expanding the list of causes of Purtscher's or Purtscher-like retinopathies. In the presence of significant uremia and absence of previously known association, the authors postulate that the sudden surge of uremia causes increase of endothelin-1 (a potent vasoconstrictor), resulting in downstream endothelin-induced vasculopathy with subsequent occlusion of the pre-capillary arteriolar network.

Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity

PubMed Central

Shaw, Lynn Calvin; Li Calzi, Sergio; Li, Nan; Moldovan, Leni; Sengupta-Caballero, Nilanjana; Quigley, Judith Lindsey; Ivan, Mircea; Jun, Bokkyoo; Bazan, Nicolas G.; Boulton, Michael Edwin; Busik, Julia; Neu, Josef; Grant, Maria B.

2018-01-01

Purpose Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Methods Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene (neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA). Results With Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins. Conclusions Arg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP. PMID:29490339

Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity.

PubMed

Shaw, Lynn Calvin; Li Calzi, Sergio; Li, Nan; Moldovan, Leni; Sengupta-Caballero, Nilanjana; Quigley, Judith Lindsey; Ivan, Mircea; Jun, Bokkyoo; Bazan, Nicolas G; Boulton, Michael Edwin; Busik, Julia; Neu, Josef; Grant, Maria B

2018-02-01

Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene (neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA). With Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins. Arg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP.

Plantar Fascia Thickness is Longitudinally Associated with Retinopathy and Renal Dysfunction: A Prospective Study from Adolescence to Adulthood

PubMed Central

Benitez-Aguirre, Paul Z.; Craig, Maria E.; Jenkins, Alicia J.; Gallego, Patricia H.; Cusumano, Janine; Duffin, Anthony C.; Hing, Stephen; Donaghue, Kim C.

2012-01-01

Aim The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). Methods We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997–2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). Results Median (interquartile range) age at baseline was 15.1 (13.4–16.8) years, and median follow-up was 8.3 (7.0–9.5) years, with 4 (3–6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 µg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd–4th quartiles, χ2 = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0–10.3] and early renal dysfunction (OR 3.2, CI 1.3–8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. Conclusions In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation. PMID:22538146

Plantar fascia thickness is longitudinally associated with retinopathy and renal dysfunction: a prospective study from adolescence to adulthood.

PubMed

Benitez-Aguirre, Paul Z; Craig, Maria E; Jenkins, Alicia J; Gallego, Patricia H; Cusumano, Janine; Duffin, Anthony C; Hing, Stephen; Donaghue, Kim C

2012-03-01

The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997-2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). Median (interquartile range) age at baseline was 15.1 (13.4-16.8) years, and median follow-up was 8.3 (7.0-9.5) years, with 4 (3-6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 μg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd-4th quartiles, χ(2) = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0-10.3] and early renal dysfunction (OR 3.2, CI 1.3-8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation. © 2012 Diabetes Technology Society.

Oxygen and Oxygen Toxicity: The Birth of Concepts

PubMed Central

Zhu, Hong; Traore, Kassim; Santo, Arben; Trush, Michael A.; Li, Y. Robert

2018-01-01

Molecular dioxygen (O2) is an essential element of aerobic life, yet incomplete reduction or excitation of O2 during aerobic metabolisms generates diverse oxygen-containing reactive species, commonly known as reactive oxygen species (ROS). On the one hand, ROS pose a serious threat to aerobic organisms via inducing oxidative damage to cellular constituents. On the other hand, these reactive species, when their generation is under homeostatic control, also play important physiological roles (e.g., constituting an important component of immunity and participating in redox signaling). This article defines oxygen and the key facts about oxygen, and discusses the relationship between oxygen and the emergence of early animals on Earth. The article then describes the discovery of oxygen by three historical figures and examines the birth of the concepts of oxygen toxicity and the underlying free radical mechanisms. The article ends with a brief introduction to the emerging field of ROS-mediated redox signaling and physiological responses. PMID:29707642

The Diabetic Retinopathy Screening Workflow: Potential for Smartphone Imaging.

PubMed

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

2015-11-23

Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems' use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound. © 2015 Diabetes Technology Society.

Nitric oxide and oxidative stress is associated with severity of diabetic retinopathy and retinal structural alterations.

PubMed

Sharma, Shashi; Saxena, Sandeep; Srivastav, Khushboo; Shukla, Rajendra K; Mishra, Nibha; Meyer, Carsten H; Kruzliak, Peter; Khanna, Vinay K

2015-07-01

The aim of the study was to determine plasma nitric oxide (NO) and lipid peroxide (LPO) levels in diabetic retinopathy and its association with severity of disease. Prospective observational study. A total of 60 consecutive cases and 20 healthy controls were included. Severity of retinopathy was graded according to early treatment diabetic retinopathy study (ETDRS) classification. Photoreceptor inner segment ellipsoid band (ISel) disruption and retinal pigment epithelium (RPE) alteration were graded using spectral domain optical coherence tomography. Data were statistically analyzed. Plasma thiobarbituric acid reactive substances, NO assay and reduced glutathione (GSH) were measured using standard protocol. Increased severity of diabetic retinopathy was significantly associated with increase in plasma levels of LPO (P < 0.05), NO (P < 0.001) and decrease in plasma levels of GSH (P < 0.0001), ISel disruption (P < 0.001) and RPE topographic alteration (P < 0.01). Increased plasma NO levels are associated with increased severity of diabetic retinopathy. For the first time, it has been demonstrated that increased plasma LPO, NO and decreased GSH levels are associated with in vivo structural changes in inner segment ellipsoid and RPE. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

To report a case of unilateral proliferative retinopathy following noncerebral malaria with Plasmodium falciparum in Southern India.

PubMed

Verma, Aditya; Krishna, M S

2015-01-01

The retinopathy in association with malaria fever described so far includes retinal hemorrhages, vessel changes, retinal discoloration/whitening and papilledema. Malaria retinopathy has been mostly described in severe cases, associated with Plasmodium falciparum, correlating the patho-physiology of retinal and cerebral manifestations. We report an unusual case of proliferative retinopathy as a manifestation of malaria fever, caused by P. falciparum with no cerebral involvement. The patient had features of unilateral retinal vascular occlusion with proliferative changes and vitreous hemorrhage. To the best of our knowledge, such a case has never been reported so far in the literature. This report highlights the possible occurrence of severe proliferative changes associated with malaria fever, which if diagnosed early can prevent possible blindness.

Automated Detection of Diabetic Retinopathy using Deep Learning.

PubMed

Lam, Carson; Yi, Darvin; Guo, Margaret; Lindsey, Tony

2018-01-01

Diabetic retinopathy is a leading cause of blindness among working-age adults. Early detection of this condition is critical for good prognosis. In this paper, we demonstrate the use of convolutional neural networks (CNNs) on color fundus images for the recognition task of diabetic retinopathy staging. Our network models achieved test metric performance comparable to baseline literature results, with validation sensitivity of 95%. We additionally explored multinomial classification models, and demonstrate that errors primarily occur in the misclassification of mild disease as normal due to the CNNs inability to detect subtle disease features. We discovered that preprocessing with contrast limited adaptive histogram equalization and ensuring dataset fidelity by expert verification of class labels improves recognition of subtle features. Transfer learning on pretrained GoogLeNet and AlexNet models from ImageNet improved peak test set accuracies to 74.5%, 68.8%, and 57.2% on 2-ary, 3-ary, and 4-ary classification models, respectively.

Dyslipidemia and Diabetic Retinopathy

PubMed Central

Chang, Yo-Chen; Wu, Wen-Chuan

2013-01-01

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

Colour vision in AIDS patients without HIV retinopathy.

PubMed

Sommerhalder, J; Baglivo, E; Barbey, C; Hirschel, B; Roth, A; Pelizzone, M

1998-11-01

Patients suffering from AIDS develop ocular complications, the most frequent being HIV retinopathy. It is however not clear, if functional visual impairments can be observed as early indicators of ocular complications, before clinical diagnosis of HIV retinopathy is made at fundus examination. To address this issue, we measured colour vision in a group of 49 AIDS subjects with normal clinical fundi using the 'two equation method'. This method, combining red-green Rayleigh and the blue-green Moreland metameric matches, enables more complete and quantitative assessments of colour vision than those based on pigmentary tests. Data were collected on our computer controlled colorimeter and compared to those of normal subjects. While most AIDS subjects without HIV retinopathy demonstrated normal colour vision, a significant portion of them had wider matches than normal subjects (11% for the Rayleigh equation and 16% for the Moreland equation). Furthermore, matching ranges of the Moreland equation were significantly correlated with CD4 lymphocyte counts. Patients with low CD4 values tended to produce larger matching ranges than the patients with high CD4 values. A within subject study on 17 patients confirmed this trend and showed that the patients who increased/decreased their CD4 blood counts generally improved/impaired their colour discrimination in the Moreland match. No such correlation was found between the matching ranges of the Rayleigh equation and the CD4 counts. These results show that colour discrimination is slightly reduced in some AIDS subjects, although there are no detectable ocular complications. They also suggest two different types of colour vision impairments in AIDS patients without retinopathy: one reversible process affecting colour discrimination in the blue-green range; and another irreversible process affecting colour discrimination in the red-green range.

Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials

PubMed Central

Pedraza, Eileen; Coronel, Maria M.; Fraker, Christopher A.; Ricordi, Camillo; Stabler, Cherie L.

2012-01-01

A major hindrance in engineering tissues containing highly metabolically active cells is the insufficient oxygenation of these implants, which results in dying or dysfunctional cells in portions of the graft. The development of methods to increase oxygen availability within tissue-engineered implants, particularly during the early engraftment period, would serve to allay hypoxia-induced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated solid calcium peroxide, PDMS-CaO2. Encapsulation of solid peroxide within hydrophobic PDMS resulted in sustained oxygen generation, whereby a single disk generated oxygen for more than 6 wk at an average rate of 0.026 mM per day. The ability of this oxygen-generating material to support cell survival was evaluated using a β cell line and pancreatic rat islets. The presence of a single PDMS-CaO2 disk eliminated hypoxia-induced cell dysfunction and death for both cell types, resulting in metabolic function and glucose-dependent insulin secretion comparable to that in normoxic controls. A single PDMS-CaO2 disk also sustained enhanced β cell proliferation for more than 3 wk under hypoxic culture conditions. Incorporation of these materials within 3D constructs illustrated the benefits of these materials to prevent the development of detrimental oxygen gradients within large implants. Mathematical simulations permitted accurate prediction of oxygen gradients within 3D constructs and highlighted conditions under which supplementation of oxygen tension would serve to benefit cellular viability. Given the generality of this platform, the translation of these materials to other cell-based implants, as well as ischemic tissues in general, is envisioned. PMID:22371586

Retinopathy of prematurity: Revisiting incidence and risk factors from Oman compared to other countries.

PubMed

Reyes, Zenaida Soriano; Al-Mulaabed, Sharef Waadallah; Bataclan, Flordeliz; Montemayor, Cheryl; Ganesh, Anuradha; Al-Zuhaibi, Sanaa; Al-Waili, Huda; Al-Wahibi, Fatma

2017-01-01

The purpose of this study is to determine the incidence of retinopathy of prematurity (ROP) and the maternal/neonatal risk factors at a tertiary care hospital in Oman, compared to other countries. A retrospective analysis of premature neonates born with gestational age (GA) 24-32 weeks at Sultan Qaboos University Hospital, Oman, from January 2007 to December 2010. Maternal and neonatal in-hospital course was retrieved. The incidence of ROP was reported. Risk factors analyses were performed using univariate and multivariate statistics. A total of 171 neonates (57% males, 43% females) were included for analysis. The incidence of ROP (any stage) was 69/171 (40.4%). Infants with ROP had significantly lower GA (27.7±2 weeks) compared to non-ROP group (30.2±1.7 weeks), P < 0.001),P < 0.001) and significantly lower birth weight (BW) (948 ± 242 g in ROP group vs. 1348 ± 283 g in non-ROP group;P < 0.001). Other significant risk factors associated with ROP were: small for GA, respiratory distress syndrome, requirement for ventilation, duration of ventilation or oxygen therapy, bronchopulmonary dysplasia, hyperglycemia, late onset sepsis (clinical or proven), necrotizing enterocolitis, patent ductus arteriosus, seizures, and number of blood transfusions. There was no significant difference in maternal characteristics between the ROP and non-ROP groups except that mothers of infants with ROP were found to be significantly younger. Logistic regression analysis revealed early GA, low BW, duration of Oxygen therapy, and late-onset clinical or proven sepsis as independent risk factors. ROP is still commonly encountered in neonatal practice in Oman and other countries. Early GA, low BW, and prolonged oxygen therapy continue to be the main risk factors associated with the occurrence of ROP in our setting. In addition, an important preventable risk factor identified in our cohort includes clinical or proven late-onset sepsis.

Lesion detection in ultra-wide field retinal images for diabetic retinopathy diagnosis

NASA Astrophysics Data System (ADS)

Levenkova, Anastasia; Sowmya, Arcot; Kalloniatis, Michael; Ly, Angelica; Ho, Arthur

2018-02-01

Diabetic retinopathy (DR) leads to irreversible vision loss. Diagnosis and staging of DR is usually based on the presence, number, location and type of retinal lesions. Ultra-wide field (UWF) digital scanning laser technology provides an opportunity for computer-aided DR lesion detection. High-resolution UWF images (3078×2702 pixels) may allow detection of more clinically relevant retinopathy in comparison with conventional retinal images as UWF imaging covers a 200° retinal area, versus 45° by conventional cameras. Current approaches to DR diagnosis that analyze 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) retinal images provide similar results to UWF imaging. However, in 40% of cases, more retinopathy was found outside the 7- field ETDRS fields by UWF and in 10% of cases, retinopathy was reclassified as more severe. The reason is that UWF images examine both the central retina and more peripheral regions. We propose an algorithm for automatic detection and classification of DR lesions such as cotton wool spots, exudates, microaneurysms and haemorrhages in UWF images. The algorithm uses convolutional neural network (CNN) as a feature extractor and classifies the feature vectors extracted from colour-composite UWF images using a support vector machine (SVM). The main contribution includes detection of four types of DR lesions in the peripheral retina for diagnostic purposes. The evaluation dataset contains 146 UWF images. The proposed method for detection of DR lesion subtypes in UWF images using two scenarios for transfer learning achieved AUC ≈ 80%. Data was split at the patient level to validate the proposed algorithm.

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

PubMed

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

2016-05-01

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

Purtscher-like retinopathy in systemic lupus erythematosus.

PubMed

Wu, Chan; Dai, Rongping; Dong, Fangtian; Wang, Qian

2014-12-01

To investigate clinical characteristics of Purtscher-like retinopathy and its clinical implications among patients with systemic lupus erythematosus (SLE). Observational case series. setting: Tertiary medical center. patient population: Patients with SLE who were diagnosed with Purtscher-like retinopathy between 2002 and 2013. observation procedures: Assessment and follow-up in the ophthalmology department. main outcome measure: Visual acuity and funduscopic examination at presentation and at 6 month follow-up, with analysis of the association between Purtscher-like retinopathy and other systemic involvement of SLE and overall disease activity. Among 5688 patients with SLE evaluated, 8 cases of Purtscher-like retinopathy were diagnosed. Typical fundus abnormalities included Purtscher flecken, cotton-wool spots, retinal hemorrhages, macular edema, optic disk swelling, and a pseudo-cherry red spot. Fluorescein angiography abnormalities included areas of capillary nonperfusion corresponding to the retinal whitening, late leakage, peripapillary staining, precapillary occlusion, and slower filling of vessels. The prevalence of central nervous system lupus was significantly higher among those with Purtscher-like retinopathy (6/8) than among 240 patients randomly sampled from those without Purtscher-like retinopathy. A very high SLE Disease Activity Index (≥20) was present in all 8 patients with Purtscher-like retinopathy. All patients received corticosteroids combined with immunosuppressants. For the majority of patients, optic atrophy developed during follow-up with persistent low visual acuity. As a rare and severe ophthalmic complication of SLE, Purtscher-like retinopathy was associated with central nervous system lupus and highly active disease. Visual acuity recovery was usually poor despite prompt treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Conceptual analysis of diabetic retinopathy in Ayurveda.

PubMed

Sahoo, Prasanta Kumar; Fiaz, Shamsa

Inclusion of Prameha among the eight major disorders in Charaka Samhita shows the importance of the disease given by ancient seers. The risk of development of blindness in diabetics increases by 20-25 times as compared to the normal population. High prevalence rate of Diabetic Retinopathy (34.6%), proliferative diabetic retinopathy (7%), diabetic macular edema (6.8%), and Vision threatening Diabetic retinopathy (10.2%) in diabetics was great concerns which led to search and analyze the disease process on the basis of modern pathogenesis and different Timirvyadhi mentioned in Ayurvedic authoritative texts. Thus the present study endeavors to discuss the similarities and differences among the various components of Prameha/Madhumehajanya Timir with Diabetic retinopathy and its stages. To establish a probable etiopathogenesis of the disease from Ayurveda prospective, all the important literature of both modern medicine and Ayurveda along with online sources were searched and analyzed. All the three dosha along with Raktadosha and Saptadhatu with four internal Dristipatals of eye are affected in Madhumehajanya timir in different stages of the disease. Avarana and Dhatu kshaya too have important role in development of diabetic retinopathy due to prolonged and uncontrolled hyperglycemia. Agnimandya related Ama formation has a role in pathology of diabetic retinopathy which is quite similar to oxidative theory of diabetic retinopathy explained in modern pathology. Urdhwaga raktapitta, Ojas kshaya, Raktavritta vata, and Pranavritta vyana are other causes in development of diabetic retinopathy. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Pericentral retinopathy and racial differences in hydroxychloroquine toxicity.

PubMed

Melles, Ronald B; Marmor, Michael F

2015-01-01

To describe patterns of hydroxychloroquine retinopathy distinct from the classic parafoveal (bull's eye) maculopathy. Retrospective case series. Patients from a large multi-provider group practice and a smaller university referral practice diagnosed with hydroxychloroquine retinopathy. Patients with widespread or "end-stage" retinopathy were excluded. Review of ophthalmic studies (fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, multifocal electroretinography, visual fields) and classification of retinopathy into 1 of 3 patterns: parafoveal (retinal changes 2°-6° from the fovea), pericentral (retinal changes ≥ 8° from the fovea), or mixed (retinal changes in both parafoveal and pericentral areas). Relative frequency of different patterns of hydroxychloroquine retinopathy and comparison of risk factors. Of 201 total patients (18% Asian) with hydroxychloroquine retinopathy, 153 (76%) had typical parafoveal changes, 24 (12%) also had a zone of pericentral damage, and 24 (12%) had pericentral retinopathy without any parafoveal damage. Pericentral retinopathy alone was seen in 50% of Asian patients but only in 2% of white patients. Patients with the pericentral pattern were taking hydroxychloroquine for a somewhat longer duration (19.5 vs. 15.0 years, P < 0.01) and took a larger cumulative dose (2186 vs. 1813 g, P = 0.02) than patients with the parafoveal pattern, but they were diagnosed at a more severe stage of toxicity. Hydroxychloroquine retinopathy does not always develop in a parafoveal (bull's eye) pattern, and a pericentral pattern of damage is especially prevalent among Asian patients. Screening practices may need to be adjusted to recognize pericentral and parafoveal hydroxychloroquine retinopathy. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Physical activity and its correlation to diabetic retinopathy.

PubMed

Praidou, Anna; Harris, Martin; Niakas, Dimitrios; Labiris, Georgios

2017-02-01

The lack of physical activity, along with obesity, smoking, hypertension and hyperglycaemia are considered as risk factors for the occurrence of diseases such as diabetes. Primary objective of the study was to investigate potential correlation between physical activity and diabetic retinopathy. Three hundred and twenty patients were included in the study: 240 patients with diabetes type 2 (80 patients with mild to moderate non-proliferative diabetic retinopathy, 80 patients with severe to very severe non-proliferative diabetic retinopathy and 80 ones with proliferative diabetic retinopathy) were compared with 80 non-diabetic patients (control group). Physical activity of patients was assessed by the international physical activity questionnaire (IPAQ, 2002). HbA1c and BMI were also measured in diabetic patients. Group comparisons were attempted for levels of physical activity and sedentary behavior. Total physical activity was decreased in patients with severe to very severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy as compared to patients with mild to moderate non-proliferative diabetic retinopathy and to the control group (p<0.05). Significant negative correlation was detected between HbA1c levels, BMI and physical activity (both p<0.05). Moreover, significant negative correlation between the severity of diabetic retinopathy and physical activity has been demonstrated (p<0.05). Increased physical activity is associated with less severe levels of diabetic retinopathy, independent of the effects of HbA1c and BMI. Copyright © 2016 Elsevier Inc. All rights reserved.

Postnatal Growth and Retinopathy of Prematurity Study: Rationale, Design, and Subject Characteristics.

PubMed

Binenbaum, Gil; Tomlinson, Lauren A

2017-02-01

Postnatal-growth-based predictive models demonstrate strong potential for improving the low specificity of retinopathy of prematurity (ROP) screening. Prior studies are limited by inadequate sample size. We sought to study a sufficiently large cohort of at-risk infants to enable development of a model with highly precise estimates of sensitivity for severe ROP. The Postnatal Growth and ROP (G-ROP) Study was a multicenter retrospective cohort study of infants at 30 North American hospitals during 2006-2012. A total of 65 G-ROP-certified abstractors submitted data to a secure, web-based database. Data included ROP examination findings, treatments, complications, daily weight measurements, daily oxygen supplementation, maternal/infant demographics, medical comorbidities, surgical events, and weekly nutrition. Data quality was monitored with system validation rules, data audits, and discrepancy algorithms. Of 11,261 screened infants, 8334 were enrolled, and 2927 had insufficient data due to transfer, discharge, or death. Of the enrolled infants, 90% (7483) had a known ROP outcome and were included in the study. Median birth weight was 1070 g (range 310-3000g) and mean gestational age 28 weeks (range 22-35 weeks). Severe ROP (Early Treatment of Retinopathy type 1 or 2) developed in 931 infants (12.5%). Successful incorporation of a predictive model into ROP screening requires confidence that it will capture cases of severe ROP. This dataset provides power to estimate sensitivity with half-confidence interval width of less than 0.5%, determined by the high number of severe ROP cases. The G-ROP Study represents a large, diverse cohort of at-risk infants undergoing ROP screening. It will facilitate evaluation of growth-based algorithms to improve efficiency of ROP screening.

Association of A1C and Fasting Plasma Glucose Levels With Diabetic Retinopathy Prevalence in the U.S. Population

PubMed Central

Cheng, Yiling J.; Gregg, Edward W.; Geiss, Linda S.; Imperatore, Giuseppina; Williams, Desmond E.; Zhang, Xinzhi; Albright, Ann L.; Cowie, Catherine C.; Klein, Ronald; Saaddine, Jinan B.

2009-01-01

OBJECTIVE To examine the association of A1C levels and fasting plasma glucose (FPG) with diabetic retinopathy in the U.S. population and to compare the ability of the two glycemic measures to discriminate between people with and without retinopathy. RESEARCH DESIGN AND METHODS This study included 1,066 individuals aged ≥40 years from the 2005–2006 National Health and Nutrition Examination Survey. A1C, FPG, and 45° color digital retinal images were assessed. Retinopathy was defined as a level ≥14 on the Early Treatment Diabetic Retinopathy Study severity scale. We used joinpoint regression to identify linear inflections of prevalence of retinopathy in the association between A1C and FPG. RESULTS The overall prevalence of retinopathy was 11%, which is appreciably lower than the prevalence in people with diagnosed diabetes (36%). There was a sharp increase in retinopathy prevalence in those with A1C ≥5.5% or FPG ≥5.8 mmol/l. After excluding 144 people using hypoglycemic medication, the change points for the greatest increase in retinopathy prevalence were A1C 5.5% and FPG 7.0 mmol/l. The coefficients of variation were 15.6 for A1C and 28.8 for FPG. Based on the areas under the receiver operating characteristic curves, A1C was a stronger discriminator of retinopathy (0.71 [95% CI 0.66–0.76]) than FPG (0.65 [0.60 – 0.70], P for difference = 0.009). CONCLUSIONS The steepest increase in retinopathy prevalence occurs among individuals with A1C ≥5.5% and FPG ≥5.8 mmol/l. A1C discriminates prevalence of retinopathy better than FPG. PMID:19875604

Diabetic retinopathy grading by digital curvelet transform.

PubMed

Hajeb Mohammad Alipour, Shirin; Rabbani, Hossein; Akhlaghi, Mohammad Reza

2012-01-01

One of the major complications of diabetes is diabetic retinopathy. As manual analysis and diagnosis of large amount of images are time consuming, automatic detection and grading of diabetic retinopathy are desired. In this paper, we use fundus fluorescein angiography and color fundus images simultaneously, extract 6 features employing curvelet transform, and feed them to support vector machine in order to determine diabetic retinopathy severity stages. These features are area of blood vessels, area, regularity of foveal avascular zone, and the number of micro-aneurisms therein, total number of micro-aneurisms, and area of exudates. In order to extract exudates and vessels, we respectively modify curvelet coefficients of color fundus images and angiograms. The end points of extracted vessels in predefined region of interest based on optic disk are connected together to segment foveal avascular zone region. To extract micro-aneurisms from angiogram, first extracted vessels are subtracted from original image, and after removing detected background by morphological operators and enhancing bright small pixels, micro-aneurisms are detected. 70 patients were involved in this study to classify diabetic retinopathy into 3 groups, that is, (1) no diabetic retinopathy, (2) mild/moderate nonproliferative diabetic retinopathy, (3) severe nonproliferative/proliferative diabetic retinopathy, and our simulations show that the proposed system has sensitivity and specificity of 100% for grading.

Automatic diabetic retinopathy classification

NASA Astrophysics Data System (ADS)

Bravo, María. A.; Arbeláez, Pablo A.

2017-11-01

Diabetic retinopathy (DR) is a disease in which the retina is damaged due to augmentation in the blood pressure of small vessels. DR is the major cause of blindness for diabetics. It has been shown that early diagnosis can play a major role in prevention of visual loss and blindness. This work proposes a computer based approach for the detection of DR in back-of-the-eye images based on the use of convolutional neural networks (CNNs). Our CNN uses deep architectures to classify Back-of-the-eye Retinal Photographs (BRP) in 5 stages of DR. Our method combines several preprocessing images of BRP to obtain an ACA score of 50.5%. Furthermore, we explore subproblems by training a larger CNN of our main classification task.

Retinal oxygen extraction in humans

NASA Astrophysics Data System (ADS)

Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

2015-10-01

Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

Retinal oxygen extraction in humans

PubMed Central

Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

2015-01-01

Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation

PubMed Central

Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

2015-01-01

The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28 ± 0.08 μL min−1 (p < 0.001), and 0.20 ± 0.04 μL min−1 (p < 0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation. Results from an oxygen diffusion model based on previous oxygen electrode measurements corroborated our in vivo observations. We believe that vis-OCT has the potential to reveal the fundamental role of oxygen metabolism in various retinal diseases. PMID:26658555

Diabetic retinopathy in two patients with congenital IGF-I deficiency (Laron syndrome).

PubMed

Laron, Zvi; Weinberger, Dov

2004-07-01

Animal and clinical studies have shown that excessive amounts of growth hormone or insulin-like growth factor-I (IGF-I) promote the development of diabetes and diabetic retinopathy. Forthwith, we present two patients with congenital IGF-I deficiency who developed type II diabetes and subsequently retinopathy. Eighteen adult patients with classical Laron syndrome (8 males, 10 females, aged 20-62 years) were followed by us since childhood or underwent fundus photography with a Nikon NF 505 instrument. Three had been treated in childhood with IGF-I, the rest were never treated, including the two patients reported. Two never-treated patients were diagnosed with type II diabetes (DM) at ages 39 and 41 respectively. There was no diabetes in the families. Oral treatment was followed by insulin injections. Metabolic control was not optimal and one patient developed proliferative diabetic retinopathy, necessitating laser surgery. He also has nephropathy and severe neuropathy. The other patient has background diabetic retinopathy and has developed, progressively, exudates, microaneurisms, hemorrhages and clinically significant macular edema. He also has subacute ischemic heart disease. Our findings show that congenital IGF-I deficiency, similar to excess, causes vascular complications of DM, denoting also that vascular endothelial growth factor can induce neovascularization in the presence of congenital IGF-I deficiency.

Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images.

PubMed

Pachiyappan, Arulmozhivarman; Das, Undurti N; Murthy, Tatavarti Vsp; Tatavarti, Rao

2012-06-13

We describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized.

Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images

PubMed Central

2012-01-01

We describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized. PMID:22695250

Fundus fluorescence Angiography in diagnosing diabetic retinopathy.

PubMed

Wang, Shuhui; Zuo, Yuqin; Wang, Ning; Tong, Bin

2017-01-01

To investigate the manifestation characteristics of fundus fluorescence angiography (FFA) and its values in diagnosing diabetic retinopathy through comparing direct ophthalmoscopy. Two hundred fifty patients (500 eyes) who were suspected as diabetic retinopathy and admitted to the hospital between February 2015 and December 2016 were selected. They underwent direct ophthalmoscopy and FFA. The manifestation characteristics of FFA in the diagnosis of diabetic retinopathy were summarized. The two examination methods were compared. In the diagnosis with direct ophthalmoscopy, 375 eyes out of 500 eyes were diagnosed as diabetic retinopathy (75%); there were 74 eyes at stage I, 88 eyes at stage II, 92 eyes at stage III, 83 eyes of stage IV, 28 eyes of stage V and 10 eyes of stage VI. In the diagnosis with FFA, 465 eyes out of 500 eyes were diagnosed as diabetic retinopathy (93%); there were 94 eyes at stage I, 110 eyes at stage II, 112 at stage III, 92 eyes at stage IV, 41 eyes at stage V and 16 eyes at stage VI. The detection rate of diabetic retinopathy using FFA was significantly higher than that using direct ophthalmoscopy (P<0.05). FFA found that 316 eyes had non-proliferative retinopathy (67.96%), 75 eyes had pre-proliferative lesions (16.13%), 149 eyes had proliferative lesions (32.04%), 135 eyes had diabetic maculopathy (29.03%) and 31 eyes had diabetic optic disc lesions (6.67%). The detection rate of diabetic retinopathy using FFA is higher than that using direct ophthalmoscopy. FFA could accurately determine clinical stage. Therefore, it is an important approach in treatment efficacy evaluation and treatment guidance, suggesting a significant application value.

IMPACT OF RETINOPATHY SCREENINGS FOR PROSPECTIVE HEART TRANSPLANT CANDIDATES.

PubMed

Simon, Shira S; Wilcox, Jane E; Lyon, Alice T; Jampol, Lee M

2017-01-01

To determine the prevalence of retinopathy among patients undergoing heart transplantation screening and to determine the impact of this finding on eligibility for transplantation. A retrospective case series was collected to perform an institutional review of all inpatient consults for dilated eye examinations on potential heart transplant candidates over 5.5 years-from March 27, 2008 to October 10, 2014. Measured outcomes included the presence or absence of retinopathy and the effect of retinopathy, if present, on a patient's eligibility for cardiac transplantation. A total of 155 heart transplant candidates underwent bedside ophthalmologic examination as part of their heart transplant candidacy workup. Retinopathy was found in 16 (10%) of these patients: diabetic retinopathy in 13 (8.4%) and hypertensive retinopathy in 3 (1.9%). None of these patients were excluded from the transplant candidacy based on the presence of retinopathy. On bedside ophthalmologic examination, retinopathy is an uncommon finding among cardiac transplant candidates. Retinopathy did not preclude transplantation in these patients. We question the utility of the present system of bedside ophthalmic consultation of heart transplant candidates. This may not be an optimal allocation of provider resources. Further studies are warranted to determine an appropriate protocol for ocular evaluation of these patients.

Diabetic retinopathy in a remote Indigenous primary healthcare population: a Central Australian diabetic retinopathy screening study in the Telehealth Eye and Associated Medical Services Network project.

PubMed

Brazionis, L; Jenkins, A; Keech, A; Ryan, C; Brown, A; Boffa, J; Bursell, S

2018-05-01

To determine diabetic retinopathy prevalence and severity among remote Indigenous Australians. A cross-sectional diabetic retinopathy screening study of Indigenous adults with Type 2 diabetes was conducted by locally trained non-ophthalmic retinal imagers in a remote Aboriginal community-controlled primary healthcare clinic in Central Australia and certified non-ophthalmic graders in a retinal grading centre in Melbourne, Australia. The main outcome measure was prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy. Among 301 participants (33% male), gradable image rates were 78.7% (n = 237) for diabetic retinopathy and 83.1% (n = 250) for diabetic macular oedema, and 77.7% (n = 234) were gradable for both diabetic retinopathy and diabetic macular oedema. For the gradable subset, the median (range) age was 48 (19-86) years and known diabetes duration 9.0 (0-24) years. The prevalence of diabetic retinopathy was 47% (n = 110) and for diabetic macular oedema it was 14.4% (n = 36). In the fully gradable imaging studies, sight-threatening diabetic retinopathy prevalence was 16.2% (n = 38): 14.1% (n = 33) for clinically significant macular oedema, 1.3% (n = 3) for proliferative diabetic retinopathy and 0.9% (n = 2) for both. Sight-threatening diabetic retinopathy had been treated in 78% of detected cases. A novel telemedicine diabetic retinopathy screening service detected a higher prevalence of 'any' diabetic retinopathy and sight-threatening diabetic retinopathy in a remote primary care setting than reported in earlier surveys among Indigenous and non-Indigenous populations. Whether the observed high prevalence of diabetic retinopathy was attributable to greater detection, increasing diabetic retinopathy prevalence, local factors, or a combination of these requires further investigation and, potentially, specific primary care guidelines for diabetic retinopathy management in remote Australia. Clinical Trials registration number: Australia and

CHOROIDAL THICKNESS IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Laíns, Inês; Talcott, Katherine E; Santos, Ana R; Marques, João H; Gil, Pedro; Gil, João; Figueira, João; Husain, Deeba; Kim, Ivana K; Miller, Joan W; Silva, Rufino; Miller, John B

2018-01-01

To compare the choroidal thickness (CT) of diabetic eyes (different stages of disease) with controls, using swept-source optical coherence tomography. A multicenter, prospective, cross-sectional study of diabetic and nondiabetic subjects using swept-source optical coherence tomography imaging. Choroidal thickness maps, according to the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, were obtained using automated software. Mean CT was calculated as the mean value within the ETDRS grid, and central CT as the mean in the central 1 mm. Diabetic eyes were divided into four groups: no diabetic retinopathy (No DR), nonproliferative DR (NPDR), NPDR with diabetic macular edema (NPDR + DME), and proliferative DR (PDR). Multilevel mixed linear models were performed for analyses. The authors included 50 control and 160 diabetic eyes (n = 27 No DR, n = 51 NPDR, n = 61 NPDR + DME, and n = 21 PDR). Mean CT (ß = -42.9, P = 0.022) and central CT (ß = -50.2, P = 0.013) were statistically significantly thinner in PDR eyes compared with controls, even after adjusting for confounding factors. Controlling for age, DR eyes presented a significantly decreased central CT than diabetic eyes without retinopathy (β = -36.2, P = 0.009). Swept-source optical coherence tomography demonstrates a significant reduction of CT in PDR compared with controls. In the foveal region, the choroid appears to be thinner in DR eyes than in diabetic eyes without retinopathy.

Arterial blood oxygen saturation during blood pressure cuff-induced hypoperfusion

NASA Astrophysics Data System (ADS)

Kyriacou, P. A.; Shafqat, K.; Pal, S. K.

2007-10-01

Pulse oximetry has been one of the most significant technological advances in clinical monitoring in the last two decades. Pulse oximetry is a non-invasive photometric technique that provides information about the arterial blood oxygen saturation (SpO2) and heart rate, and has widespread clinical applications. When peripheral perfusion is poor, as in states of hypovolaemia, hypothermia and vasoconstriction, oxygenation readings become unreliable or cease. The problem arises because conventional pulse oximetry sensors must be attached to the most peripheral parts of the body, such as finger, ear or toe, where pulsatile flow is most easily compromised. Pulse oximeters estimate arterial oxygen saturation by shining light at two different wavelengths, red and infrared, through vascular tissue. In this method the ac pulsatile photoplethysmographic (PPG) signal associated with cardiac contraction is assumed to be attributable solely to the arterial blood component. The amplitudes of the red and infrared ac PPG signals are sensitive to changes in arterial oxygen saturation because of differences in the light absorption of oxygenated and deoxygenated haemoglobin at these two wavelengths. From the ratios of these amplitudes, and the corresponding dc photoplethysmographic components, arterial blood oxygen saturation (SpO2) is estimated. Hence, the technique of pulse oximetry relies on the presence of adequate peripheral arterial pulsations, which are detected as photoplethysmographic (PPG) signals. The aim of this study was to investigate the effect of pressure cuff-induced hypoperfusion on photoplethysmographic signals and arterial blood oxygen saturation using a custom made finger blood oxygen saturation PPG/SpO2 sensor and a commercial finger pulse oximeter. Blood oxygen saturation values from the custom oxygen saturation sensor and a commercial finger oxygen saturation sensor were recorded from 14 healthy volunteers at various induced brachial pressures. Both pulse

Choroidal Thinning Associated With Hydroxychloroquine Retinopathy.

PubMed

Ahn, Seong Joon; Ryu, So Jung; Joung, Joo Young; Lee, Byung Ro

2017-11-01

To investigate choroidal thickness in patients using hydroxychloroquine (HCQ) and compare choroidal thickness between eyes with and without HCQ retinopathy. Retrospective case series. Setting: Institutional. We included 124 patients with systemic lupus erythematosus or rheumatoid arthritis who were treated with HCQ. The patients were divided into an HCQ retinopathy group and a control group, according to the presence or absence of HCQ retinopathy. Total choroidal thickness and choriocapillaris-equivalent thickness were measured manually by 2 independent investigators using swept-source optical coherence tomography (SS-OCT; DRI-OCT, Topcon Inc, Tokyo, Japan). These measurements were made at the fovea and at nasal and temporal locations 0.5, 1.5, and 3 mm from the fovea. Medium-to-large vessel layer thickness was calculated accordingly. The thicknesses were compared between the HCQ retinopathy and control groups. We performed correlation analyses between choroidal thicknesses and details regarding HCQ use. Total choroidal thickness and choriocapillaris-equivalent thickness. Choroidal thicknesses were significantly decreased (P < .05) in the HCQ retinopathy group compared to the control group, except at the temporal choroid 1.5 mm from the fovea. Choriocapillaris-equivalent thicknesses were significantly different in all choroidal locations between the groups. In contrast, the medium-to-large vessel layer thickness was only significantly different at a few locations. The cumulative dose/body weight was significantly correlated with subfoveal choroidal and choriocapillaris-equivalent thicknesses (both P = .001). The association between presence of HCQ retinopathy and choroidal thicknesses was also statistically significant after adjusting for age, diagnosis for HCQ use, refractive errors, and duration of HCQ use (P = .001 and P = .003 for subfoveal choroidal and choriocapillaris-equivalent thickness, respectively). These results all suggest that HCQ retinopathy is

Operational Components of Telemedicine Programs for Diabetic Retinopathy.

PubMed

Horton, Mark B; Silva, Paolo S; Cavallerano, Jerry D; Aiello, Lloyd Paul

2016-12-01

Diabetic retinopathy is a leading cause of new-onset vision loss worldwide. Treatments supported by large clinical trials are effective in preserving vision, but many persons do not receive timely diagnosis and treatment of diabetic retinopathy, which is typically asymptomatic when most treatable. Telemedicine evaluation to identify diabetic retinopathy has the potential to improve access to care and improve outcomes, but incomplete implementation of published standards creates a risk to program utility and sustainability. In a prior article, we reviewed the literature regarding the impact of imaging device, number and size of retinal images, pupil dilation, type of image grader, and diagnostic accuracy on telemedicine assessment for diabetic retinopathy. This article reviews the literature regarding the impact of automated image grading, cost effectiveness, program standards, and quality assurance (QA) on telemedicine assessment of diabetic retinopathy. Telemedicine assessment of diabetic retinopathy has the potential to preserve vision, but greater attention to development and implementation of standards is needed to better realize its potential.

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. Diabetic retinopathy (DR), the leading cause of blindness among diabetic patients can develop without any serious symptoms therefore the early detection is crucial. Because of the increasing prevalence there is a high need for improved screening methods able to diagnose DR as soon as possible. The non-invasive collection and the relatively high protein concentration make the tear fluid a good source for biomarker discovery helping the early diagnosis. In this work we have reviewed the administration of advanced proteomics techniques used in tear biomarker studies and the identified biomarkers with potential to improve the already existing screening methods for DR detection. Copyright © 2016 Elsevier B.V. All rights reserved.

Receptor for advanced glycation end product expression in experimental diabetic retinopathy.

PubMed

Wang, Yumei; Vom Hagen, Franziska; Pfister, Frederick; Bierhaus, Angelika; Feng, Yuxi; Gans, Reinhold; Hammes, Hans-Peter

2008-04-01

The advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway is involved in the pathogenesis of diabetic microvascular damage. The special distribution of RAGE and its engagement has an impact on the development of diabetic retinopathy. In the present study, we used immunofluorescence and confocal laser microscopy to study RAGE expression with special emphasis on Müller glia in Sprague Dawley rats. RAGE expression was low in nondiabetic retinae and was found in ganglion cells and Müller cell end feet. In diabetic retinae, upregulated RAGE was predominantly expressed in retinal glia. Since Müller cells are important in the regulation of important features of early retinal vascular damage, such as vascular permeability, homeostasis, and response to stress, RAGE appears to be a central modulator in diabetic retinopathy.

Results of a diabetic retinopathy screening. Risk markers analysis.

PubMed

Ancochea, G; Martín Sánchez, M D

2016-01-01

To identify risk markers for retinopathy in patients from our geographic area, and to compare them with those published in other studies. To design a screening interval strategy, taking into account these results, and compare it with intervals suggested in published studies. Cross-sectional observational study on 383 diabetic patients with no previous retinopathy diagnosis, who were screened for diabetic retinopathy. An analysis was made on the possible association between patient factors and presence of retinopathy. A greater probability for finding retinopathy in diabetic patients was associated to insulin treatment in our study, with a statistical significance level of 95%. In patients with less than 10year onset of their diabetes, only mild retinopathy without macular oedema was found. Insulin treatment and time of onset of diabetes should be taken into account when designing efficient screening strategies for diabetic retinopathy. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity study: findings at 4 to 6 years of age.

PubMed

Quinn, Graham E; Dobson, Velma; Davitt, Bradley V; Wallace, David K; Hardy, Robert J; Tung, Betty; Lai, Dejian; Good, William V

2013-04-01

To report the prevalence of myopia and high myopia in children <6 years of age born preterm with birth weights <1251 g who developed high-risk prethreshold retinopathy of prematurity and who participated in the Early Treatment for Retinopathy of Prematurity trial. Surviving children from the cohort of 401 participants who had developed high-risk prethreshold ROP in one or both eyes underwent cycloplegic retinoscopy at 6 and 9 months corrected age and yearly between 2 and 6 years postnatal age. Eyes were randomized to receive treatment at high-risk prethreshold ROP or conventional management with treatment only if threshold ROP developed. Myopia (spherical equivalent ≥0.25 D) or high myopia (≥5.00 D) in eyes at 4-, 5-, and 6-year examinations was reported. At ages 4, 5, and 6 years, there was no difference in the percentage of eyes with myopia (range, 64.8%-69.9%) and eyes with high myopia (range, 35.3%-39.4%) between earlier treated and conventionally managed eyes. Approximately two-thirds of eyes with high-risk prethreshold ROP during the neonatal period are likely to be myopic into the preschool and early school years. In addition, the increase in the proportion of eyes with high myopia that had been observed in both earlier-treated and conventionally managed eyes between ages 6 months and 3 years does not continue between ages 3 and 6 years. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Placental Growth Factor Contributes to Micro-Vascular Abnormalization and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

PubMed Central

Kowalczuk, Laura; Touchard, Elodie; Omri, Samy; Jonet, Laurent; Klein, Christophe; Valamanes, Fatemeh; Berdugo, Marianne; Bigey, Pascal; Massin, Pascale; Jeanny, Jean-Claude; Behar-Cohen, Francine

2011-01-01

Objective There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1). Materials and Methods pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis. Results After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation. Conclusion This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease. PMID:21408222

Sensitivity and specificity of Norwegian optometrists' evaluation of diabetic retinopathy in single-field retinal images - a cross-sectional experimental study.

PubMed

Sundling, Vibeke; Gulbrandsen, Pål; Straand, Jørund

2013-01-10

In the working age group, diabetic retinopathy is a leading cause of visual impairment. Regular eye examinations and early treatment of retinopathy can prevent visual loss, so screening for diabetic retinopathy is cost-effective. Dilated retinal digital photography with the additional use of ophthalmoscopy is the most effective and robust method of diabetic retinopathy screening. The aim of this study was to estimate the sensitivity and specificity of diabetic retinopathy screening when performed by Norwegian optometrists. This study employed a cross-sectional experimental design. Seventy-four optometrists working in private optometric practice were asked to screen 14 single-field retinal images for possible diabetic retinopathy. The screening was undertaken using a web-based visual identification and management of ophthalmological conditions (VIMOC) examination. The images used in the VIMOC examination were selected from a population survey and had been previously examined by two independent ophthalmologists. In order to establish a "gold standard", images were only chosen for use in the VIMOC examination if they had elicited diagnostic agreement between the two independent ophthalmologists. To reduce the possibility of falsely high specificity occurring by chance, half the presented images were of retinas that were not affected by diabetic retinopathy. Sensitivity and specificity for diabetic retinopathy was calculated with 95% confidence intervals (CIs). The mean (95%CI) sensitivity for identifying eyes with any diabetic retinopathy was 67% (62% to 72%). The mean (95%CI) specificity for identifying eyes without diabetic retinopathy was 84% (80% to 89%). The mean (95%CI) sensitivity for identifying eyes with mild non-proliferative diabetic retinopathy or moderate non-proliferative diabetes was 54% (47% to 61%) and 100%, respectively. Only four optometrists (5%) met the required standard of at least 80% sensitivity and 95% specificity that has been previously set

Oxygen Saturation of Retinal Vessels in All Stages of Diabetic Retinopathy and Correlation to Ultra-Wide Field Fluorescein Angiography.

PubMed

Guduru, Abhilash; Martz, Teresa G; Waters, Alexa; Kshirsagar, Abhijit V; Garg, Seema

2016-10-01

The purpose of this study was to determine retinal hemoglobin oxygen saturation (SO2) in patients with diabetic retinopathy (DR) using retinal oximetry (RO) and to correlate the degree of retinal ischemia using intravenous fluorescein angiography (IVFA). This is a single-center cross-sectional cohort study. Twenty-seven controls and 60 adult patients with diabetes mellitus (16 without DR and 44 with DR) were enrolled. Patients were stratified according to DR severity. Using RO, SO2 was measured in major retinal arterioles (SaO2) and venules (SvO2). Using IVFA, the percentage of retinal ischemia in 31 patients with DR was calculated and correlated with RO. Pairwise one-way analysis of variance (ANOVA) showed a significant increase in SaO2 and SvO2 in patients with proliferative DR (PDR) compared with controls (SaO2: PDR, 100 ± 7% vs. controls, 91 ± 4% [P = 0.003]; SvO2: PDR, 66 ± 11% vs. controls, 53 ± 6% [P < 0.00001]). The percentage of retinal ischemia also increased with DR severity: ANOVA showed a significant difference in retinal ischemia between all categories of nonproliferative DR vs. PDR: 2.31 ± 2% vs. 7.92 ± 9% (P = 0.017), respectively. Pearson two-tailed correlation showed significant correlation between SaO2 and ischemia (R = 0.467, P = 0.011). Hemoglobin oxygen saturation of retinal arterioles and venules increases with DR severity; SaO2 correlates with increasing ischemia measured by IVFA. Retinal oximetry may complement current imaging strategies to noninvasively augment the diagnosis and risk stratification of patients with diabetes.

Quantitative Assessment of Retinopathy Using Multi-parameter Image Analysis

PubMed Central

Ghanian, Zahra; Staniszewski, Kevin; Jamali, Nasim; Sepehr, Reyhaneh; Wang, Shoujian; Sorenson, Christine M.; Sheibani, Nader; Ranji, Mahsa

2016-01-01

A multi-parameter quantification method was implemented to quantify retinal vascular injuries in microscopic images of clinically relevant eye diseases. This method was applied to wholemount retinal trypsin digest images of diabetic Akita/+, and bcl-2 knocked out mice models. Five unique features of retinal vasculature were extracted to monitor early structural changes and retinopathy, as well as quantifying the disease progression. Our approach was validated through simulations of retinal images. Results showed fewer number of cells (P = 5.1205e-05), greater population ratios of endothelial cells to pericytes (PCs) (P = 5.1772e-04; an indicator of PC loss), higher fractal dimension (P = 8.2202e-05), smaller vessel coverage (P = 1.4214e-05), and greater number of acellular capillaries (P = 7.0414e-04) for diabetic retina as compared to normal retina. Quantification using the present method would be helpful in evaluating physiological and pathological retinopathy in a high-throughput and reproducible manner. PMID:27186534

Importance of Considering the Middle Capillary Plexus on OCT Angiography in Diabetic Retinopathy.

PubMed

Onishi, Alex C; Nesper, Peter L; Roberts, Philipp K; Moharram, Ganna A; Chai, Haitao; Liu, Lei; Jampol, Lee M; Fawzi, Amani A

2018-04-01

To quantify microvasculature changes in the superficial (SCP), middle (MCP), and deep capillary plexuses (DCP) in diabetic retinopathy (DR). Retrospective cross-sectional study at a tertiary academic referral center, in which 26 controls (44 eyes), 27 diabetic subjects without retinopathy (44 eyes), 32 subjects with nonproliferative retinopathy (52 eyes), and 27 subjects with proliferative retinopathy (40 eyes) were imaged with optical coherence tomography angiography (OCTA). Outcome measures included parafoveal vessel density (VD), percentage area of nonperfusion (PAN), and adjusted flow index (AFI) at the different plexuses. MCP VD and MCP AFI decreased with worsening DR, while PAN increased, mirroring changes within the DCP. The fitted regression line for MCP and DCP AFI were significantly different than the SCP, while DCP PAN differed from SCP PAN with disease progression. Higher SCP AFI and PAN were different in eyes with diabetes without retinopathy compared with controls. Unexpectedly, sex was found to independently influence MCP VD and AFI with worsening disease. OCTA parameters in the MCP and DCP displayed parallel changes with DR progression, different from the SCP, emphasizing the importance of physiologic considerations in the retinal capillaries. Thus, segmentation protocols that include the MCP within the SCP may be confounded. A difference in DCP PAN with worsening DR was unmasked relative to a prior study that included the MCP with SCP. We confirm that SCP AFI and PAN may serve as early indicators of microvascular changes in DR and identify an interaction between sex and the MCP deserving further study.

Diabetic Retinopathy: Pathophysiology and Treatments.

PubMed

Wang, Wei; Lo, Amy C Y

2018-06-20

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM). It has long been recognized as a microvascular disease. The diagnosis of DR relies on the detection of microvascular lesions. The treatment of DR remains challenging. The advent of anti-vascular endothelial growth factor (VEGF) therapy demonstrated remarkable clinical benefits in DR patients; however, the majority of patients failed to achieve clinically-significant visual improvement. Therefore, there is an urgent need for the development of new treatments. Laboratory and clinical evidence showed that in addition to microvascular changes, inflammation and retinal neurodegeneration may contribute to diabetic retinal damage in the early stages of DR. Further investigation of the underlying molecular mechanisms may provide targets for the development of new early interventions. Here, we present a review of the current understanding and new insights into pathophysiology in DR, as well as clinical treatments for DR patients. Recent laboratory findings and related clinical trials are also reviewed.

ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.

PubMed

Rothschild, Pierre-Raphaël; Salah, Sawsen; Berdugo, Marianne; Gélizé, Emmanuelle; Delaunay, Kimberley; Naud, Marie-Christine; Klein, Christophe; Moulin, Alexandre; Savoldelli, Michèle; Bergin, Ciara; Jeanny, Jean-Claude; Jonet, Laurent; Arsenijevic, Yvan; Behar-Cohen, Francine; Crisanti, Patricia

2017-08-18

In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

Microaneurysm turnover is a predictor of diabetic retinopathy progression.

PubMed

Pappuru, Rajeev K R; Ribeiro, Luísa; Lobo, Conceição; Alves, Dalila; Cunha-Vaz, José

2018-04-26

To analyse retinopathy phenotypes and microaneurysm (MA) turnover in mild non-proliferative diabetic retinopathy (NPDR) as predictors of progression to diabetic central-involved macular oedema (CIMO) in patients with type 2 diabetes mellitus (DM) in two different ethnic populations. 205 patients with type 2 DM and mild NPDR were followed in a prospective observational study for 2 years or until development of CIMO, in two centres from different regions of the world. Ophthalmological examinations, including best-corrected visual acuity (BCVA), fundus photography with RetmarkerDR analysis, and optical coherence tomography (OCT), were performed at baseline and 6 12 and 24 months. 158 eyes/patients reached either the study endpoint, CIMO (24) or performed the last study visit (24-month visit) without developing CIMO (134). From the eyes/patients in analysis, 27 eyes (17.1%) progressed to more advanced ETDRS (Early Treatment Diabetic Retinopathy Study) levels: 6 progressed to mild NPDR (level 35), 15 progressed to moderate NPDR (level 43), 5 progressed to moderately severe NPDR (level 47) and 1 progressed to high risk PDR (level 71). Worsening in ETDRS level is associated with phenotype C (p=0.005). From the 130 eyes/patients with a low MA turnover, 18 (13.8%) eyes/patients had an increase in ETDRS level, and from the 19 eyes/patients with a high MA turnover, 9 (47.4%) had an increase in ETDRS level (p<0.001). Eyes in the initial stages of diabetic retinopathy show different phenotypes with different risks for progression to CIMO. In phenotype C, MA turnover correlates with ETDRS grading worsening and development of CIMO. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical Components of Telemedicine Programs for Diabetic Retinopathy.

PubMed

Horton, Mark B; Silva, Paolo S; Cavallerano, Jerry D; Aiello, Lloyd Paul

2016-12-01

Diabetic retinopathy is a leading cause of new-onset vision loss worldwide. Treatments supported by large clinical trials are effective in preserving vision, but many persons do not receive timely diagnosis and treatment of diabetic retinopathy, which is typically asymptomatic when most treatable. Telemedicine evaluation to identify diabetic retinopathy has the potential to improve access to care, but there are no universal standards regarding camera choice or protocol for ocular telemedicine. We review the literature regarding the impact of imaging device, number and size of retinal images, pupil dilation, type of image grader, and diagnostic accuracy on telemedicine assessment for diabetic retinopathy. Telemedicine assessment of diabetic retinopathy has the potential to preserve vision, but further development of telemedicine specific technology and standardization of operations are needed to better realize its potential.

New pharmacologic approaches to treating diabetic retinopathy.

PubMed

Ryan, Gina J

2007-09-01

The goal of treatment of diabetic retinopathy, limitations of laser photocoagulation, endpoints used in clinical studies of diabetic retinopathy treatments, and the mechanism of action, efficacy, and safety of several new and emerging therapies targeting the biochemical pathways that link chronic hyperglycemia with microvascular damage in patients with diabetic retinopathy are discussed. Improving or preserving vision is the primary goal of treatment for diabetic retinopathy. Limitations of laser photocoagulation include a lack of efficacy in some cases, discomfort from the procedure, the need for repeated treatment, and a risk of retinal damage and scarring. Visual acuity, quality of life, and macular thickness are used as endpoints in clinical studies of diabetic retinopathy treatments. Microvascular damage in patients with chronic hyperglycemia is mediated by interrelated pathways involving aldose reductase, advanced glycation end products, protein kinase C (PKC), and vascular endothelial growth factor (VEGF). Oral aldose reductase inhibitors have been studied with some success only in patients with diabetic peripheral neuropathy. The oral PKC inhibitor midostaurin and oral selective PKC beta inhibitor ruboxistaurin appear promising for improving or maintaining visual acuity, with gastrointestinal complaints the most commonly reported adverse effects. Intra-vitreal injection of corticosteroids or VEGF inhibitors is associated with short-lived improvement in or maintenance of visual acuity, a need for repeated injection, and a risk of local adverse effects. A variety of promising new therapies for diabetic retinopathy targeting the biochemical pathways that cause microvascular damage are under investigation. Additional clinical research is needed to determine the role of these new therapies in treating diabetic retinopathy.

Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal.

PubMed

Song, Youngkyu; Cho, Gyunggoo; Chun, Song-I; Baek, Jin Hee; Cho, HyungJoon; Kim, Young Ro; Park, Sung Bin; Kim, Jeong Kon

2014-07-01

In comparison to the well-documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood-oxygen-level-dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen-treated serum were 0.22 mM(-1) · s(-1) and 0.19 mM(-1) · s(-1) , respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18-42% of measured brain regions, voxels with accompanying significant decreases in both the T(*)2 (-12.1% to -19.4%) and T1 (-5.8% to -3.3%) relaxation times. In contrast, the T(*)2 relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41-50% of the measured brain), which reflected a hyperoxygenation-induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia-driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen-induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, -9.8% to -12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia. Copyright © 2014

Mechanisms controlling the oxygen consumption in experimentally induced hypochloremic alkalosis in calves.

PubMed

Cambier, Carole; Clerbaux, Thierry; Amory, Hélène; Detry, Bruno; Florquin, Sandra; Marville, Vincent; Frans, Albert; Gustin, Pascal

2002-01-01

The study was carried out on healthy Friesian calves (n = 10) aged between 10 and 30 days. Hypochloremia and alkalosis were induced by intravenous administration of furosemide and isotonic sodium bicarbonate. The venous and arterial blood samples were collected repeatedly. 2,3-diphosphoglycerate (2,3-DPG), hemoglobin and plasmatic chloride concentrations were determined. The red blood cell chloride concentration was also calculated. pH, PCO2 and PO2 were measured in arterial and mixed venous blood. The oxygen equilibrium curve (OEC) was measured in standard conditions. The correspondence of the OEC to the arterial and mixed venous compartments was calculated, taking blood temperature, pH and PCO2 values into account. The oxygen exchange fraction (OEF%), corresponding to the degree of blood desaturation between the arterial and mixed venous compartments and the amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated from the arterial and mixed venous OEC, combined with PO2 and hemoglobin concentration. Oxygen delivery (DO2) was calculated using the arterial oxygen content, the cardiac output measured by thermodilution, and the body weight of the animal. The oxygen consumption (VO2) was derived from the cardiac output, OEF Vol% and body weight values. Despite the plasma hypochloremia, the erythrocyte chloride concentration was not influenced by furosemide and sodium bicarbonate infusion. Due to the alkalosis-induced increase in the 2,3-DPG, the standard OEC was shifted to the right, allowing oxygen to dissociate from hemoglobin more rapidly. These changes opposed the increased affinity of hemoglobin for oxygen induced by alkalosis. Moreover, respiratory acidosis, hemoconcentration, and the slight decrease in the partial oxygen pressure in mixed venous blood (Pvo2) tended to improve the OEF Vol% and maintain the oxygen consumption in a physiological range while the cardiac output, and the oxygen delivery were significantly decreased

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants.

PubMed

Porcelli, Peter J; Weaver, R Grey

2010-06-01

Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. Evaluate relationship between early postnatal nutriture and ROP surgery. Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates. Copyright 2010 Elsevier Ltd. All rights reserved.

Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension.

PubMed

Papazova, Diana A; Friederich-Persson, Malou; Joles, Jaap A; Verhaar, Marianne C

2015-01-01

Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (Po2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney Qo2, cortical Po2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 ± 3.3 vs. 0.9 ± 0.4 pmol O2 · s(-1)· mg protein(-1), P < 0.05) and increased whole kidney Qo2 (55 ± 16 vs. 33 ± 10 μmol O2/min, P < 0.05). Corticomedullary Po2 was lower in TX compared with 1K-CON (30 ± 13 vs. 47 ± 4 μM, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Qo2, Po2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage. Copyright © 2015 the American Physiological Society.

Screening and treatments using telemedicine in retinopathy of prematurity

PubMed Central

Thanos, Aristomenis; Yonekawa, Yoshihiro; Todorich, Bozho; Moshfeghi, Darius M; Trese, Michael T

2016-01-01

Several studies have validated the role of telemedicine as a new powerful screening and diagnostic tool for retinal disorders, such as diabetic retinopathy and retinopathy of prematurity. With regard to retinopathy of prematurity, bedside examination with binocular indirect ophthalmoscopy has been the gold standard technique for screening, yet with several limitations. Herein, we review the current evidence that supports the role of telemedicine for the screening of infants with retinopathy of prematurity. PMID:28539810

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN PURTSCHER RETINOPATHY.

PubMed

Rivera-De La Parra, David; Fromow-Guerra, Jans

2017-12-27

To describe paracentral acute middle maculopathy associated with Purtscher retinopathy, particularly in Purtscher flecken lesions as a retinal complication in a case secondary to fractures of long bones. Case report. A 16-year-old boy with bilateral paracentral scotomata presented with bilateral paracentral acute middle maculopathy as part of Purtscher retinopathy in both eyes as consequence of tibia and fibula fractures. Paracentral acute middle maculopathy is one of the optical coherence tomography findings in Purtscher retinopathy.

Malarial retinopathy in northern Nigerian children.

PubMed

Mohammed, I; Ibrahim, U Y; Mukhtar, M; Farouq, Z; Obiagwu, P N; Yashua, A H

2010-01-01

This is a prospective study involving two centres. Children younger than 16 years old who had severe malaria underwent funduscopy. In one centre, direct ophthalmoscopy was performed by both an ophthalmologist and a non-ophthalmologist physician. At the other, two ophthalmologists performed a funduscopy on each patient using different methods (one using direct and the other indirect ophthalmoscopy). The objective was to determine the frequency of retinopathy and evaluate the effectiveness of direct ophthalmoscopy in detecting retinopathy in constantly dilated eyes. Of 62 children seen at both centres, 37% were found to have malarial retinopathy. Macula whitening was the most common finding. There was substantial agreement between the ophthalmologists using either the direct or indirect ophthalmoscopy techniques (Kappa value 0.604). However, at the centre using only direct ophthalmoscopy, there was poor agreement between the ophthalmologist and the non-ophthalmologist (kappa value -0.244). Direct ophthalmoscopy seemed to be effective in detecting malarial retinopathy, but only when performed by experienced personnel.

Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial.

PubMed

Vaucher, Yvonne E; Peralta-Carcelen, Myriam; Finer, Neil N; Carlo, Waldemar A; Gantz, Marie G; Walsh, Michele C; Laptook, Abbot R; Yoder, Bradley A; Faix, Roger G; Das, Abhik; Schibler, Kurt; Rich, Wade; Newman, Nancy S; Vohr, Betty R; Yolton, Kimberly; Heyne, Roy J; Wilson-Costello, Deanne E; Evans, Patricia W; Goldstein, Ricki F; Acarregui, Michael J; Adams-Chapman, Ira; Pappas, Athina; Hintz, Susan R; Poindexter, Brenda; Dusick, Anna M; McGowan, Elisabeth C; Ehrenkranz, Richard A; Bodnar, Anna; Bauer, Charles R; Fuller, Janell; O'Shea, T Michael; Myers, Gary J; Higgins, Rosemary D

2012-12-27

Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses. Using a 2-by-2 factorial design, we randomly assigned infants born between 24 weeks 0 days and 27 weeks 6 days of gestation to early CPAP with a limited ventilation strategy or early surfactant administration and to lower or higher target ranges of oxygen saturation (85 to 89% or 91 to 95%). The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age. The primary outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18 to 22 months of corrected age. Death or neurodevelopmental impairment occurred in 27.9% of the infants in the CPAP group (173 of 621 infants), versus 29.9% of those in the surfactant group (183 of 613) (relative risk, 0.93; 95% confidence interval [CI], 0.78 to 1.10; P=0.38), and in 30.2% of the infants in the lower-oxygen-saturation group (185 of 612), versus 27.5% of those in the higher-oxygen-saturation group (171 of 622) (relative risk, 1.12; 95% CI, 0.94 to 1.32; P=0.21). Mortality was increased with the lower-oxygen-saturation target (22.1%, vs. 18.2% with the higher-oxygen-saturation target; relative risk, 1.25; 95% CI, 1.00 to 1.55; P=0.046). We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation. (Funded by the Eunice Kennedy

Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes.

PubMed

Nathan, David M; Bebu, Ionut; Hainsworth, Dean; Klein, Ronald; Tamborlane, William; Lorenzi, Gayle; Gubitosi-Klug, Rose; Lachin, John M

2017-04-20

In patients who have had type 1 diabetes for 5 years, current recommendations regarding screening for diabetic retinopathy include annual dilated retinal examinations to detect proliferative retinopathy or clinically significant macular edema, both of which require timely intervention to preserve vision. During 30 years of the Diabetes Control and Complications Trial (DCCT) and its longitudinal follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, retinal photography was performed at intervals of 6 months to 4 years. We used retinal photographs from the DCCT/EDIC study to develop a rational screening frequency for retinopathy. Markov modeling was used to determine the likelihood of progression to proliferative diabetic retinopathy or clinically significant macular edema in patients with various initial retinopathy levels (no retinopathy or mild, moderate, or severe nonproliferative diabetic retinopathy). The models included recognized risk factors for progression of retinopathy. Overall, the probability of progression to proliferative diabetic retinopathy or clinically significant macular edema was limited to approximately 5% between retinal screening examinations at 4 years among patients who had no retinopathy, 3 years among those with mild retinopathy, 6 months among those with moderate retinopathy, and 3 months among those with severe nonproliferative diabetic retinopathy. The risk of progression was also closely related to mean glycated hemoglobin levels. The risk of progression from no retinopathy to proliferative diabetic retinopathy or clinically significant macular edema was 1.0% over 5 years among patients with a glycated hemoglobin level of 6%, as compared with 4.3% over 3 years among patients with a glycated hemoglobin level of 10%. Over a 20-year period, the frequency of eye examinations was 58% lower with our practical, evidence-based schedule than with routine annual examinations, which resulted in substantial cost savings

Imaging in diabetic retinopathy.

PubMed

Salz, David A; Witkin, Andre J

2015-01-01

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

Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy.

PubMed

Wessel, Matthew M; Aaker, Grant D; Parlitsis, George; Cho, Minhee; D'Amico, Donald J; Kiss, Szilárd

2012-04-01

To evaluate patients with diabetic retinopathy using ultra-wide-field fluorescein angiography and to compare the visualized retinal pathology with that seen on an overly of conventional 7 standard field (7SF) imaging. Two hundred and eighteen eyes of 118 diabetic patients who underwent diagnostic fluorescein angiography using the Optos Optomap Panoramic 200A imaging system were included. The visualized area of the retina, retinal nonperfusion, retinal neovascularization, and panretinal photocoagulation were quantified by two independent masked graders. The respective areas identified on the ultra-wide-field fluorescein angiography image were compared with an overly of a modified 7SF image as outlined in the Early Treatment Diabetic Retinopathy Study. Ultra-wide-field fluorescein angiograms imaging, on average, demonstrated 3.2 times more total retinal surface area than 7SF. When compared with 7SF, ultra-wide-field fluorescein angiography showed 3.9 times more nonperfusion (P < 0.001), 1.9 times more neovascularization (P = 0.036), and 3.8 times more panretinal photocoagulation (P < 0.001). In 22 eyes (10%), ultra-wide-field fluorescein angiography demonstrated retinal pathology (including nonperfusion and neovascularization) not evident in an 7SF overly. Compared with conventional 7SF imaging, ultra-wide-field fluorescein angiography reveals significantly more retinal vascular pathology in patients with diabetic retinopathy. Improved retinal visualization may alter the classification of diabetic retinopathy and may therefore influence follow-up and treatment of these patients.

The value of digital imaging in diabetic retinopathy.

PubMed

Sharp, P F; Olson, J; Strachan, F; Hipwell, J; Ludbrook, A; O'Donnell, M; Wallace, S; Goatman, K; Grant, A; Waugh, N; McHardy, K; Forrester, J V

2003-01-01

To assess the performance of digital imaging, compared with other modalities, in screening for and monitoring the development of diabetic retinopathy. All imaging was acquired at a hospital assessment clinic. Subsequently, study optometrists examined the patients in their own premises. A subset of patients also had fluorescein angiography performed every 6 months. Research clinic at the hospital eye clinic and optometrists' own premises. Study comprised 103 patients who had type 1 diabetes mellitus, 481 had type 2 diabetes mellitus and two had secondary diabetes mellitus; 157 (26.8%) had some form of retinopathy ('any') and 58 (9.9%) had referable retinopathy. A repeat assessment was carried out of all patients 1 year after their initial assessment. Patients who had more severe forms of retinopathy were monitored more frequently for evidence of progression. Detection of retinopathy, progression of retinopathy and determination of when treatment is required. Manual grading of 35-mm colour slides produced the highest sensitivity and specificity figures, with optometrist examination recording most false negatives. Manual and automated analysis of digital images had intermediate sensitivity. Both manual grading of 35-mm colour slides and digital images gave sensitivities of over 90% with few false positives. Digital imaging produced 50% fewer ungradable images than colour slides. This part of the study was limited as patients with the more severe levels of retinopathy opted for treatment. There was an increase in the number of microaneurysms in those patients who developed from mild to moderate. There was no difference between the turnover rate of either new or regressed microaneurysms for patients with mild or with sight-threatening retinopathy. It was not possible in this study to ascertain whether digital imaging systems determine when treatment is warranted. In the context of a national screening programme for referable retinopathy, digital imaging is an effective

Regulation of singlet oxygen-induced apoptosis by cytosolic NADP+-dependent isocitrate dehydrogenase.

PubMed

Kim, Sun Yee; Lee, Su Min; Tak, Jean Kyoung; Choi, Kyeong Sook; Kwon, Taeg Kyu; Park, Jeen-Woo

2007-08-01

Singlet oxygen is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules and it also promotes deleterious processes such as cell death. Recently, we demonstrated that the control of redox balance and the cellular defense against oxidative damage are the primary functions of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) through supplying NADPH for antioxidant systems. In this report, we demonstrate that modulation of IDPc activity in HL-60 cells regulates singlet oxygen-induced apoptosis. When we examined the protective role of IDPc against singlet oxygen-induced apoptosis with HL-60 cells transfected with the cDNA for mouse IDPc in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPc expressed in target cells and their susceptibility to apoptosis. The results suggest that IDPc plays an important protective role in apoptosis of HL-60 cells induced by singlet oxygen.

[Population-based study of diabetic retinopathy in Wolfsburg].

PubMed

Hesse, L; Grüsser, M; Hoffstadt, K; Jörgens, V; Hartmann, P; Kroll, P

2001-11-01

Since November 1997 the complete documentation of an ophthalmological examination of diabetics has been annually subsidized by the Volkswagen Corporation Health Maintenance Organization (VW-HMO). The results of an annual ophthalmological examination were recorded in a standardised history sheet developed by the Initiative Group for Early Detection of Diabetic Eye Diseases. These data included visual acuity, intraocular pressure, lens status and a description of fundus abnormalities. Within 26 months ophthalmological examinations of 2,801 patients were completed which represented 4.5% of all VW-HMO insured patients. On average, patients suffered from diabetes for 9.6 years (SD +/- 8.3), artificial intraocular lenses were present in 357 eyes (6.4%) and 1,216 eyes (12.0%) were diagnosed with cataract or posterior capsule opacification impairing visual acuity. Out of 263 patients younger than 40 years old, 18.8% had a mild or moderate and 3.3% a severe non-proliferative diabetic retinopathy (NPDR). A proliferative diabetic retinopathy (PDR) was found in 2.2% of the younger patients. Of 2,228 patients aged 40 years and older, 11.9% had a mild or moderate and 2.6% a severe NPDR. In 0.9% of this group PDR was diagnosed. An annual ophthalmological screening based on a survey sheet of the Initiative Group was successfully introduced. For the first time a population-based evaluation on the prevalence of diabetic retinopathy was carried out for inhabitants of a German city. The prevalence of PDR was found to be lower than previously published in comparable studied.

Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

PubMed

Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

2017-01-01

Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

PubMed

Chen, Eric; Brown, David M; Benz, Matthew S; Fish, Richard H; Wong, Tien P; Kim, Rosa Y; Major, James C

2010-10-21

While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

A Machine Learning Ensemble Classifier for Early Prediction of Diabetic Retinopathy.

PubMed

S K, Somasundaram; P, Alli

2017-11-09

The main complication of diabetes is Diabetic retinopathy (DR), retinal vascular disease and it leads to the blindness. Regular screening for early DR disease detection is considered as an intensive labor and resource oriented task. Therefore, automatic detection of DR diseases is performed only by using the computational technique is the great solution. An automatic method is more reliable to determine the presence of an abnormality in Fundus images (FI) but, the classification process is poorly performed. Recently, few research works have been designed for analyzing texture discrimination capacity in FI to distinguish the healthy images. However, the feature extraction (FE) process was not performed well, due to the high dimensionality. Therefore, to identify retinal features for DR disease diagnosis and early detection using Machine Learning and Ensemble Classification method, called, Machine Learning Bagging Ensemble Classifier (ML-BEC) is designed. The ML-BEC method comprises of two stages. The first stage in ML-BEC method comprises extraction of the candidate objects from Retinal Images (RI). The candidate objects or the features for DR disease diagnosis include blood vessels, optic nerve, neural tissue, neuroretinal rim, optic disc size, thickness and variance. These features are initially extracted by applying Machine Learning technique called, t-distributed Stochastic Neighbor Embedding (t-SNE). Besides, t-SNE generates a probability distribution across high-dimensional images where the images are separated into similar and dissimilar pairs. Then, t-SNE describes a similar probability distribution across the points in the low-dimensional map. This lessens the Kullback-Leibler divergence among two distributions regarding the locations of the points on the map. The second stage comprises of application of ensemble classifiers to the extracted features for providing accurate analysis of digital FI using machine learning. In this stage, an automatic detection

New Therapeutic Approaches in Diabetic Retinopathy

PubMed Central

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

2015-01-01

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

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

PubMed

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

2012-01-01

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. 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. 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. 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 therapies also changed the abundance of

New Views on the Early Evolution of Oxygen in the Galaxy

NASA Astrophysics Data System (ADS)

Rebolo, R.; Israelian, G.; García López, R. J.

We have performed a detailed oxygen abundance analysis of 23 metal-poor (-3.0 < [Fe/H] < -0.3) unevolved halo stars and one giant through the OH bands in the near UV, using high-resolution echelle spectra. Oxygen is found to be overabundant with respect to iron in these stars, with the [O/Fe] ratio increasing from 0.6 to 1 between [Fe/H] = -1.5 and -3.0. The behavior of the oxygen overabundance with respect to [Fe/H] is similar to that seen in previous works based on the OI IR triplet data (Abia & Rebolo 1989; Tomkin et al. 1992; Cavallo, Pilachowski, & Rebolo 1997). Contrary to the previously accepted picture, our oxygen abundances, derived from low-excitation OH lines, agree well with those derived from high-excitation lines of the triplet. For nine stars in common with Tomkin et al. we obtain a mean difference of 0.00 plus or minus 0.11dex with respect to the abundances determined from the triplet using the same stellar parameters and model photospheres. Our new results show a smooth extension of the Edvardsson et al.'s (1993) [O/Fe] versus metallicity curve to much lower abundances. The oxygen abundances of unevolved stars when compared with values in the literature for giants of similar metallicity imply that the latter may have suffered a process of oxygen depletion. It appears that unevolved metal-poor stars are better tracers of the early chemical evolution of the Galaxy. The extrapolation of our results to very low metallicities indicates that the ratio of oxygen to iron emerging from the first Type II SNe in the early Galaxy was indeed close to unity. The higher [O/Fe] ratios we find in dwarfs has an impact on the age determination of globular clusters, and suggest that current age estimates have to be reduced by about 1-2 Gyr.

Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

PubMed

Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

2016-06-01

Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy. Copyright © 2016 the American Physiological Society.

Oxygen-induced recombination centers in as-grown Czochralski silicon crystals

NASA Technical Reports Server (NTRS)

Nauka, K.; Gatos, H. C.; Lagowski, J.

1983-01-01

Simultaneous quantitative microprofiles of the interstitial oxygen concentration and of the excess carrier lifetime are obtained in Czochralski-grown Si crystals employing double laser absorption scanning. It is found that oxygen concentration maxima and minima along the crystal growth direction coincide with lifetime minima and maxima, respectively. Another finding is that the magnitude of oxygen-induced lifetime changes increases dramatically in going from the center to the periphery of the crystal. The findings discussed imply that 'as-grown' oxygen precipitates figure in lifetime-limiting processes.

High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes.

PubMed

Lopes-Virella, Maria F; Baker, Nathaniel L; Hunt, Kelly J; Lyons, Timothy J; Jenkins, Alicia J; Virella, Gabriel

2012-06-01

To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes. Levels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression. In unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A(1c) (HbA(1c)), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19-1.81]; AGE-LDL-IC) and 45% (1.45 [1.17-1.80]; oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12-1.66]; to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, HR for progression to PDR was 2.38 (95% CI 1.30-4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03-1.62]). Similar results were observed for oxLDL-ICs. Increased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression.

Diabetic retinopathy screening using deep neural network.

PubMed

Ramachandran, Nishanthan; Hong, Sheng Chiong; Sime, Mary J; Wilson, Graham A

2017-09-07

There is a burgeoning interest in the use of deep neural network in diabetic retinal screening. To determine whether a deep neural network could satisfactorily detect diabetic retinopathy that requires referral to an ophthalmologist from a local diabetic retinal screening programme and an international database. Retrospective audit. Diabetic retinal photos from Otago database photographed during October 2016 (485 photos), and 1200 photos from Messidor international database. Receiver operating characteristic curve to illustrate the ability of a deep neural network to identify referable diabetic retinopathy (moderate or worse diabetic retinopathy or exudates within one disc diameter of the fovea). Area under the receiver operating characteristic curve, sensitivity and specificity. For detecting referable diabetic retinopathy, the deep neural network had an area under receiver operating characteristic curve of 0.901 (95% confidence interval 0.807-0.995), with 84.6% sensitivity and 79.7% specificity for Otago and 0.980 (95% confidence interval 0.973-0.986), with 96.0% sensitivity and 90.0% specificity for Messidor. This study has shown that a deep neural network can detect referable diabetic retinopathy with sensitivities and specificities close to or better than 80% from both an international and a domestic (New Zealand) database. We believe that deep neural networks can be integrated into community screening once they can successfully detect both diabetic retinopathy and diabetic macular oedema. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Unilateral cancer-associated retinopathy: a case report.

PubMed

Javaid, Zartash; Rehan, Shahzaib M; Al-Bermani, Ayad; Payne, Gareth

2016-08-01

We write to report a rare case of unilateral cancer-associated retinopathy previously undocumented in the literature. Cancer-associated retinopathy is an uncommon paraneoplastic syndrome. It is characterised by retinal antigen autoantibodies causing rod and cone dysfunction and abnormal electroretinography findings with consequent progressive visual loss.Our patient, known to have a primary cervical intraepithelial neoplasia, presented with unilateral blurred vision as well as a disturbance in colour and night vision. Electroretinography findings of reduced a and b waves in the right eye, together with a fundoscopic appearance of a mottled retinal pigment epithelium, attenuated blood vessels and optic disc pallor were consistent with unilateral cancer-associated retinopathy. Posterior subtenon injections of triamcinolone were administered to control active disease. With periocular steroid injections, at 4 years, our patient's visual acuity remained relatively stable and her condition persisted strictly unilaterally. Cancer-associated retinopathy may be the first presenting sign of an underlying malignancy or may indicate its recurrence. Moreover, in patients with a diagnosed gynaecological malignancy, visual symptoms could reflect cancer-associated retinopathy. In our patient visual symptoms came secondary to the diagnosis of cancer. © The Author(s) 2015.

Effects of hyperbaric, normobaric and hypobaric oxygen supplementation on retinal vessels in newborn rats: a preliminary study.

PubMed

Ricci, B

1987-03-01

An experimental study was conducted on eight litters of newborn rats to evaluate the effects of supplemental oxygen administration on the retinal vasculature. The animals and their mothers were kept inside a pressure chamber and treated for the first 5 days of life. On the sixth day, they were removed and kept for five more days under room air and normobaric conditions. Three litters received continuous flow oxygen at 80% at a compression pressure of +81 kPa, one litter oxygen at 80% at a pressure of -39.5 kPa atms and three other litters received oxygen at 80% under normobaric conditions. The eighth litter was treated with room air oxygen at a compression pressure of +81 kPa. A severe retinopathy with marked retinal neovascularization was seen only in the newborn animals of the litters that received oxygen supplementation under normobaric or hypobaric conditions. Retinal vessels showed no pathological changes in the litters treated with hyperbaric normoxia or hyperoxia. It is possible to hypothesize that the prolonged period of oxygen supplementation failed to produce harmful effects on the retinal vasculature because the moderate hyperbarism caused mild retinal and choroidal vasoconstriction thus preventing excessive oxygen transport to the inner retina from the choroid during hyperoxia without inducing structural damage to the retinal tissue.

Retinopathy screening in patients with type 1 diabetes diagnosed in young age using a non-mydriatic digital stereoscopic retinal imaging.

PubMed

Minuto, N; Emmanuele, V; Vannati, M; Russo, C; Rebora, C; Panarello, S; Pistorio, A; Lorini, R; d'Annunzio, G

2012-04-01

Diabetic retinopathy seriously impairs patients' quality of life, since it represents the first cause of blindness in industrialized countries. To estimate prevalence of retinopathy in young Type 1 diabetes patients using a non-mydriatic digital stereoscopic retinal imaging (NMDSRI), and to evaluate the impact of socio-demographic, clinical, and metabolic variables. In 247 young patients glycated hemoglobin (HbA1c), gender, age, pubertal stage, presence of diabetic ketoacidosis (DKA), HLA-DQ heterodimers of susceptibility for Type 1 diabetes, and β-cell autoimmunity at clinical onset were considered. At retinopathy screening, we evaluated age, disease duration, pubertal stage, body mass index (BMI-SDS), insulin requirement, HbA1c levels, other autoimmune diseases, diabetes-related complications, serum concentrations of cholesterol and triglycerides, systolic and diastolic blood pressure. Retinopathy was found in 26/247 patients: 25 showed background retinopathy, and 1 had a sight-threatening retinopathy. A significant relationship between retinopathy and female gender (p=0.01), duration of disease ≥15 yr (p<0.0001), serum triglycerides levels >65 mg/dl (p=0.012) and mean HbA1c ≥7.5% or >9% (p=0.0014) were found at the multivariate logistic analysis. Metabolic control is the most important modifiable factor and promotion of continuous educational process to reach a good metabolic control is a cornerstone to prevent microangiopathic complications. Symptoms appear when the complication is already established; a screening program with an early diagnosis is mandatory to prevent an irreversible damage.

Automated analysis of retinal images for detection of referable diabetic retinopathy.

PubMed

Abràmoff, Michael D; Folk, James C; Han, Dennis P; Walker, Jonathan D; Williams, David F; Russell, Stephen R; Massin, Pascale; Cochener, Beatrice; Gain, Philippe; Tang, Li; Lamard, Mathieu; Moga, Daniela C; Quellec, Gwénolé; Niemeijer, Meindert

2013-03-01

The diagnostic accuracy of computer detection programs has been reported to be comparable to that of specialists and expert readers, but no computer detection programs have been validated in an independent cohort using an internationally recognized diabetic retinopathy (DR) standard. To determine the sensitivity and specificity of the Iowa Detection Program (IDP) to detect referable diabetic retinopathy (RDR). In primary care DR clinics in France, from January 1, 2005, through December 31, 2010, patients were photographed consecutively, and retinal color images were graded for retinopathy severity according to the International Clinical Diabetic Retinopathy scale and macular edema by 3 masked independent retinal specialists and regraded with adjudication until consensus. The IDP analyzed the same images at a predetermined and fixed set point. We defined RDR as more than mild nonproliferative retinopathy and/or macular edema. A total of 874 people with diabetes at risk for DR. Sensitivity and specificity of the IDP to detect RDR, area under the receiver operating characteristic curve, sensitivity and specificity of the retinal specialists' readings, and mean interobserver difference (κ). The RDR prevalence was 21.7% (95% CI, 19.0%-24.5%). The IDP sensitivity was 96.8% (95% CI, 94.4%-99.3%) and specificity was 59.4% (95% CI, 55.7%-63.0%), corresponding to 6 of 874 false-negative results (none met treatment criteria). The area under the receiver operating characteristic curve was 0.937 (95% CI, 0.916-0.959). Before adjudication and consensus, the sensitivity/specificity of the retinal specialists were 0.80/0.98, 0.71/1.00, and 0.91/0.95, and the mean intergrader κ was 0.822. The IDP has high sensitivity and specificity to detect RDR. Computer analysis of retinal photographs for DR and automated detection of RDR can be implemented safely into the DR screening pipeline, potentially improving access to screening and health care productivity and reducing visual loss

Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

PubMed Central

Mbata, Osinakachukwu; Abo El-Magd, Nada Fawzy; El-Remessy, Azza Bahram

2017-01-01

Diabetic retinopathy (DR) is the most feared ocular manifestation of diabetes. DR is characterized by progressive retinal damage that may eventually result in blindness. Clinically, this blindness is caused by progressive damage to the retinal microvasculature, which leads to ischemia, retinal swelling, and neovascularization. Retinopathy is associated with both type 1 and type 2 diabetes, with DR being the leading cause of new onset blindness in United States adults. Despite this strong association with diabetes, it must be noted that the development of retinopathy lesions is multifactorial and may occur in individuals without an established history of diabetes. Metabolic syndrome is a multifactorial condition of central obesity, hypertriglyceridemia, dyslipidemia, hypertension, fasting hyperglycemia, and insulin resistance. Although several studies examined the individual components observed in the metabolic syndrome in relation to the development of DR, there is conflicting data as to the association of the metabolic syndrome with the development of retinopathy lesions in non-diabetic subjects. This review will summarize the current literature on the evidence of the metabolic syndrome on retinopathy in subjects with and without an established history of diabetes. This review will also discuss some of the mechanisms through which metabolic syndrome can contribute to the development of retinopathy. PMID:28751954

Expression and activation of STAT3 in ischemia-induced retinopathy.

PubMed

Mechoulam, Hadas; Pierce, Eric A

2005-12-01

Signal transducer and activator of transcription protein-3 (STAT3) is a transcription factor that participates in many biological processes, including tumor angiogenesis. The expression and activation of Stat3 in the mouse model of ischemia-induced retinal neovascularization was investigated to evaluate the possible role of STAT3 in retinal vascular disease. Retinal neovascularization was induced in mice pups by exposure to hyperoxia. Gene microarrays were used to identify genes whose expression in the retina is altered at postnatal day (P)12 and P18. The relative levels of Stat3 mRNA were determined by semiquantitative RT-PCR. Stat3 protein levels and the levels of the activated form of Stat3 (pStat3) at P12, P15, P18, and P22 were determined by immunoblot analysis. Stat3 and pStat3 were demonstrated by immunofluorescence in retinal sections at P12, P15, and P18. In a series of microarray experiments, increased Stat3 mRNA levels in the retina were detected at P18. This result was validated by RT-PCR and demonstrated that Stat3 and pStat3 protein levels also increase during the development of neovascularization. Stat3 partially colocalized with blood vessels at the peak of neovascularization. pStat3 colocalized completely with blood vessels in both experimental samples and age-matched controls. pStat3 staining increased notably in the neovascular vessels at P15 and P18 and was more strongly associated with the epiretinal vessels than with inner retinal vessels. It was not detected in larger blood vessels, such as those of the optic nerve. The level of Stat3 expression increased, and pStat3 was observed in association with retinal neovascularization. Activated Stat3 was preferentially localized to neovascular retinal vessels. These data suggest that STAT3 may have a role in proliferative retinopathy.

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

PubMed

Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

Diabetic retinopathy is a neurodegenerative disorder.

PubMed

Lynch, Stephanie K; Abràmoff, Michael D

2017-10-01

Since 1875, controversy has ensued over whether ocular diabetic complications are primarily vasculopathic or neuropathic in nature. Here, we discuss the historical context by which diabetic retinopathy (DR) came to be considered a primary vasculopathy, in contrast to more recent data suggesting the importance of diabetic retinal neurodegeneration (DRN) as the primary manifestation of ocular diabetic damage. Unsurprisingly, DRN parallels other diabetic complications related to neuropathy. In general, there are three possible relationships between microvascular DR and DRN: i) microvasculopathy causes neurodegeneration; ii) neurodegeneration causes microvasculopathy or iii) they are mutually independent. The authors' group has recently produced experimental data showing that DRN precedes even the earliest manifestations of DR microvasculopathy. In combination with earlier studies showing that focal implicit time delays predicted future development of DR microvasculopathy in the same location, relationships i) and iii) are unlikely. As such, ii) is the most likely relationship: DRN is a cause of DR. Granted, additional studies are needed to confirm this hypothesis and elucidate the mechanism of diabetes-induced neurodegeneration. We conclude this review by proposing experimental approaches to test the hypothesis that DRN causes DR. If confirmed, this new paradigm may lead to earlier detection of ocular diabetic damage and earlier treatment of early DR, thereby preventing visual loss in people with diabetes. Published by Elsevier Ltd.

Retinopathy of prematurity: Revisiting incidence and risk factors from Oman compared to other countries

PubMed Central

Reyes, Zenaida Soriano; Al-Mulaabed, Sharef Waadallah; Bataclan, Flordeliz; Montemayor, Cheryl; Ganesh, Anuradha; Al-Zuhaibi, Sanaa; Al-Waili, Huda; Al-Wahibi, Fatma

2017-01-01

Purpose: The purpose of this study is to determine the incidence of retinopathy of prematurity (ROP) and the maternal/neonatal risk factors at a tertiary care hospital in Oman, compared to other countries. Patients and Methods: A retrospective analysis of premature neonates born with gestational age (GA) 24–32 weeks at Sultan Qaboos University Hospital, Oman, from January 2007 to December 2010. Maternal and neonatal in-hospital course was retrieved. The incidence of ROP was reported. Risk factors analyses were performed using univariate and multivariate statistics. Results: A total of 171 neonates (57% males, 43% females) were included for analysis. The incidence of ROP (any stage) was 69/171 (40.4%). Infants with ROP had significantly lower GA (27.7±2 weeks) compared to non-ROP group (30.2±1.7 weeks), P < 0.001),P < 0.001) and significantly lower birth weight (BW) (948 ± 242 g in ROP group vs. 1348 ± 283 g in non-ROP group;P < 0.001). Other significant risk factors associated with ROP were: small for GA, respiratory distress syndrome, requirement for ventilation, duration of ventilation or oxygen therapy, bronchopulmonary dysplasia, hyperglycemia, late onset sepsis (clinical or proven), necrotizing enterocolitis, patent ductus arteriosus, seizures, and number of blood transfusions. There was no significant difference in maternal characteristics between the ROP and non-ROP groups except that mothers of infants with ROP were found to be significantly younger. Logistic regression analysis revealed early GA, low BW, duration of Oxygen therapy, and late-onset clinical or proven sepsis as independent risk factors. Conclusion: ROP is still commonly encountered in neonatal practice in Oman and other countries. Early GA, low BW, and prolonged oxygen therapy continue to be the main risk factors associated with the occurrence of ROP in our setting. In addition, an important preventable risk factor identified in our cohort includes clinical or proven late-onset sepsis

Sensitivity and specificity of Norwegian optometrists’ evaluation of diabetic retinopathy in single-field retinal images – a cross-sectional experimental study

PubMed Central

2013-01-01

Background In the working age group, diabetic retinopathy is a leading cause of visual impairment. Regular eye examinations and early treatment of retinopathy can prevent visual loss, so screening for diabetic retinopathy is cost-effective. Dilated retinal digital photography with the additional use of ophthalmoscopy is the most effective and robust method of diabetic retinopathy screening. The aim of this study was to estimate the sensitivity and specificity of diabetic retinopathy screening when performed by Norwegian optometrists. Methods This study employed a cross-sectional experimental design. Seventy-four optometrists working in private optometric practice were asked to screen 14 single-field retinal images for possible diabetic retinopathy. The screening was undertaken using a web-based visual identification and management of ophthalmological conditions (VIMOC) examination. The images used in the VIMOC examination were selected from a population survey and had been previously examined by two independent ophthalmologists. In order to establish a “gold standard”, images were only chosen for use in the VIMOC examination if they had elicited diagnostic agreement between the two independent ophthalmologists. To reduce the possibility of falsely high specificity occurring by chance, half the presented images were of retinas that were not affected by diabetic retinopathy. Sensitivity and specificity for diabetic retinopathy was calculated with 95% confidence intervals (CIs). Results The mean (95%CI) sensitivity for identifying eyes with any diabetic retinopathy was 67% (62% to 72%). The mean (95%CI) specificity for identifying eyes without diabetic retinopathy was 84% (80% to 89%). The mean (95%CI) sensitivity for identifying eyes with mild non-proliferative diabetic retinopathy or moderate non-proliferative diabetes was 54% (47% to 61%) and 100%, respectively. Only four optometrists (5%) met the required standard of at least 80% sensitivity and 95

Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States.

PubMed

Willis, Jeffrey R; Doan, Quan V; Gleeson, Michelle; Haskova, Zdenka; Ramulu, Pradeep; Morse, Lawrence; Cantrell, Ronald A

2017-09-01

Among adults with diabetes in the United States, severe forms of diabetic retinopathy (DR) are significantly associated with a greater vision-related functional burden. To assess the functional burden of DR across severity levels in the United States. This cross-sectional study was based on 1004 participants 40 years or older with diabetes and valid ocular and sociodemographic outcomes in the National Health and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic retinopathy was based on fundus photograph grading, using the Early Treatment Diabetic Retinopathy Study severity scale. The analysis was performed from October 15, 2016, to June 15, 2017. Functional difficulties secondary to vision were assessed during a household questionnaire in which participants self-reported difficulty with reading, visuospatial tasks (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking down steps, stairs, or curbs), and driving. The main outcome measure was vision-related functional burden, which was defined as present for individuals reporting moderate or greater difficulty in any of the aforementioned tasks. Of the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95% CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI, 44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR or proliferative diabetic retinopathy (PDR). The prevalence of vision-related functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy, 20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95% CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable analysis, the odds of vision-related functional burden were significantly greater among those with severe NPDR or PDR relative to those with no retinopathy (adjusted odds ratio [aOR], 3.59; 95

Detection of perimacular red dots and blots when screening for diabetic retinopathy: Refer or not refer?

PubMed

Baltatescu, Anatolie; Striglia, Elio; Trento, Marina; Mazzeo, Aurora; Cavallo, Franco; Charrier, Lorena; Porta, Massimo

2018-05-01

Detection of microaneurysms and/or microhaemorrhages near the fovea when screening for diabetic retinopathy poses a problem because referral to retinal specialists may alarm patients and unnecessarily burden ophthalmologists. Six-month prospective study of patients found to have minimal red lesions within one disc diameter of the fovea when screened for diabetic retinopathy. Two 45° digital photographs, one centred on the macula and the other nasal including the optic disc, were taken for each eye. All patients received a 6-month re-screening appointment. Out of 70 patients, 41 returned for re-screening. Diabetic retinopathy had worsened in 3 who required referral but no treatment, was unchanged in 19 and was undetectable in the other 19. Haemoglobin A1c decreased from 7.76% ± 1.50% (61.3 ± 16.2 mmol/mol) to 6.93% ± 1.7% (52.3 ± 18.9 mmol/mol) in the patients in whom diabetic retinopathy worsened but did not change in the other groups. Baseline haemoglobin A1c ( p = 0.048) and systolic blood pressure ( p = 0.007) were lower in the patients in whom diabetic retinopathy improved, but a multivariate model including haemoglobin A1c, blood pressure and known disease duration could not identify any independent risk factor. Minimal red lesions near the fovea, though commanding early re-screening, do not require immediate referral to retinal specialists.

Feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration.

PubMed

Vaziri, Kamyar; Moshfeghi, Darius M; Moshfeghi, Andrew A

2015-03-01

Age-related macular degeneration and diabetic retinopathy are important causes of visual impairment and blindness in the world. Because of recent advances and newly available treatment modalities along with the devastating consequences associated with late stages of these diseases, much attention has been paid to the importance of early detection and improving patient access to specialist care. Telemedicine or, more specifically, digital retinal imaging utilizing telemedical technology has been proposed as an important alternative screening and management strategy to help meet this demand. In this paper, we perform a literature review and analysis that evaluates the validity and feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration. Understanding both the progress and barriers to progress that have been demonstrated in these two areas is important for future telemedicine research projects and innovations in telemedicine technology.

The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration

PubMed Central

Altmann, Christine

2018-01-01

Diabetic retinopathy is a common complication of diabetes mellitus, which appears in one third of all diabetic patients and is a prominent cause of vision loss. First discovered as a microvascular disease, intensive research in the field identified inflammation and neurodegeneration to be part of diabetic retinopathy. Microglia, the resident monocytes of the retina, are activated due to a complex interplay between the different cell types of the retina and diverse pathological pathways. The trigger for developing diabetic retinopathy is diabetes-induced hyperglycemia, accompanied by leukostasis and vascular leakages. Transcriptional changes in activated microglia, mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and extracellular signal–regulated kinase (ERK) signaling pathways, results in release of various pro-inflammatory mediators, including cytokines, chemokines, caspases and glutamate. Activated microglia additionally increased proliferation and migration. Among other consequences, these changes in microglia severely affected retinal neurons, causing increased apoptosis and subsequent thinning of the nerve fiber layer, resulting in visual loss. New potential therapeutics need to interfere with these diabetic complications even before changes in the retina are diagnosed, to prevent neuronal apoptosis and blindness in patients. PMID:29301251

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics].

PubMed

Olmos, P; Acosta, A M; Schiaffino, R; Díaz, R; Alvarado, D; O'Brien, A; Muñoz, X; Arriagada, P; Claro, J C; Vega, R; Vollrath, V; Velasco, S; Emmerich, M; Maiz, A

1999-04-01

Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

Linking Retinal Microvasculature Features With Severity of Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

PubMed

Bhanushali, Devanshi; Anegondi, Neha; Gadde, Santosh G K; Srinivasan, Priya; Chidambara, Lavanya; Yadav, Naresh Kumar; Sinha Roy, Abhijit

2016-07-01

To correlate retinal vascular features with severity and systemic indicators of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). A total of 209 eyes of 122 type 2 diabetes mellitus patients with DR and 60 eyes of 31 normal Indian subjects underwent OCTA imaging. The diabetic retinopathy patients were graded as having either nonproliferative diabetic retinopathy (NPDR: mild, moderate, and severe NPDR using Early Treatment Diabetic Retinopathy Study classification) or proliferative diabetic retinopathy (PDR). Local fractal analysis was applied to the superficial and deep retinal OCTA images. Foveal avascular zone area (FAZ in mm2); vessel density (%); spacing between large vessels (%); and spacing between small vessels (%) were analyzed. Sensitivity and specificity of vascular parameters were assessed with receiver operating characteristics (ROC) curve. Normal eyes had a significantly lower FAZ area, higher vessel density, and lower spacing between large and small vessels compared with DR grades (P < 0.001). In the superficial layer, PDR and severe NPDR had higher spacing between large vessels than mild and moderate NPDR (P = 0.04). However, mild NPDR had higher spacing between the small vessels (P < 0.001). Spacing between the large vessels in the superficial retinal layer correlated positively with HbA1c (r = 0.25, P = 0.03); fasting (r = 0.23, P = 0.02); and postprandial (r = 0.26, P = 0.03) blood sugar. The same spacing in the deep retinal vascular plexus had the highest area under the ROC curve (0.99 ± 0.01) and was uniformly elevated in all diabetic eyes (P > 0.05). Spacing between the large vessels in the superficial and deep retinal layers had superior diagnostic performance than overall vessel density.

Systemic changes and adverse effects induced by retinopathy of prematurity screening.

PubMed

Jiang, Jing-Bo; Zhang, Zhi-Wei; Zhang, Jia-Wen; Wang, Yan-Li; Nie, Chuan; Luo, Xian-Qiong

2016-01-01

To estimate the potential systemic events during and after retinopathy of prematurity (ROP) screening. A prospective and descriptive designed study was conducted to detect the physiologic and pathological changes 24h before, during, and 72h after ROP screening. Control blood pressure (BP), saturation, pulse rate, and body temperature were routinely taken at various time internals before and after screening. Adverse effects pertain to cardiovascular system, respiratory system, gastric system, urinary system and nervous system were retrospect 0-72h after ROP screening at a 24-hour interval. Totally 1254 prematurity babies receiving ROP screening during Jan. 1(st) 2013 to Dec. 31(th) 2013 were enrolled in our survey. Compared to control vital sign data taken before the examination, there was a fluctuation in the diastolic BP with the increased 3.03 mm Hg (P=0.04) after 3 doses of mydriatic drops. Immediately after the examination, there was a further 12.64 mm Hg (P<0.01) increase in systolic BP and a 7.24 mm Hg (P<0.01) in diastolic BP. The mean pulse rate during examination was 22.4 bpm (P<0.01) higher than the 133.3±9.0 bpm control level. The oxygen saturation shared an average drop of 5% (P<0.01) during screening. In prematurity with postconceptional age less than 31wk, the incidence of apnea (23.5%), necrotizing enterocolitis (NEC) (8.7%), gastric residual (25.4%) and upper digestive tract hemorrhage (6.4%) also demonstrated a significant rise (P<0.01). In our study sample, ROP screening was associated with NEC, gastric residual and upper digestive tract hemorrhage. These gastrointestinal side effects, along with breath activity pattern change and vital signs indicators fluctuation, may be results of additional stress responses.

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. © 2014 Society for Endocrinology.

Non-proliferative diabetic retinopathy symptoms detection and classification using neural network.

PubMed

Al-Jarrah, Mohammad A; Shatnawi, Hadeel

2017-08-01

Diabetic retinopathy (DR) causes blindness in the working age for people with diabetes in most countries. The increasing number of people with diabetes worldwide suggests that DR will continue to be major contributors to vision loss. Early detection of retinopathy progress in individuals with diabetes is critical for preventing visual loss. Non-proliferative DR (NPDR) is an early stage of DR. Moreover, NPDR can be classified into mild, moderate and severe. This paper proposes a novel morphology-based algorithm for detecting retinal lesions and classifying each case. First, the proposed algorithm detects the three DR lesions, namely haemorrhages, microaneurysms and exudates. Second, we defined and extracted a set of features from detected lesions. The set of selected feature emulates what physicians looked for in classifying NPDR case. Finally, we designed an artificial neural network (ANN) classifier with three layers to classify NPDR to normal, mild, moderate and severe. Bayesian regularisation and resilient backpropagation algorithms are used to train ANN. The accuracy for the proposed classifiers based on Bayesian regularisation and resilient backpropagation algorithms are 96.6 and 89.9, respectively. The obtained results are compared with results of the recent published classifier. Our proposed classifier outperforms the best in terms of sensitivity and specificity.

Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective.

PubMed

Sivaprasad, Sobha; Gupta, Bhaskar; Crosby-Nwaobi, Roxanne; Evans, Jennifer

2012-01-01

The alarming rise in diabetes prevalence is a global public health and economic problem. Diabetic retinopathy is the most common complication of diabetes and the leading cause of blindness among working-age populations in the Western world. Screening and prompt treatment of diabetic retinopathy are not top priorities in many regions of the world, because the impacts of other causes of preventable blindness remain an issue. Ethnicity is a complex, independent risk factor for diabetic retinopathy. Observations from white populations cannot be extrapolated fully to other ethnic groups. The prevalence of diabetic retinopathy, sight-threatening diabetic retinopathy, and clinically significant macular edema are higher in people of South Asian, African, Latin American, and indigenous tribal descent compared to the white population. Although all ethnic groups are susceptible to the established risk factors of diabetic retinopathy-such as length of exposure and severity of hyperglycemia, hypertension, and hyperlipidemia-ethnic-specific risk factors also may influence these rates. Such risk factors may include differential susceptibility to conventional risk factors, insulin resistance, differences in anthropometric measurements, truncal obesity, urbanization, variations in access to healthcare systems, genetic susceptibility, and epigenetics. The rates of nonproliferative diabetic retinopathy appear to be declining in the United States, supporting the observation that better medical management of diabetes and prompt treatment of sight-threatening diabetic retinopathy substantially improve the long-term diabetic retinopathy incidence; studies from other parts of the world are limited and do not mirror this finding, however. We examine the ethnicity and region-based prevalence of diabetic retinopathy around the world and highlight the need to reinforce ethnicity-based screening and treatment thresholds in diabetic retinopathy. Copyright © 2012 Elsevier Inc. All rights

Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

PubMed

Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

2018-03-01

Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Antiangiogenic effect of betaine on pathologic retinal neovascularization via suppression of reactive oxygen species mediated vascular endothelial growth factor signaling.

PubMed

Park, Sung Wook; Jun, Hyoung Oh; Kwon, Euna; Yun, Jun-Won; Kim, Jin Hyoung; Park, Young-Jun; Kang, Byeong-Cheol; Kim, Jeong Hun

2017-03-01

Reactive oxygen species (ROS) as well as vascular endothelial growth factor (VEGF) play important roles in pathologic retinal neovascularization. We investigated whether betaine inhibits pathologic retinal neovascularization in a mouse model of oxygen induced retinopathy (OIR). Betaine was intravitreally injected in OIR mice at postnatal day (P) 14. At P17, the neovascular tufts area in OIR retina was analyzed. Intravitreal injection of betaine (200μM) effectively reduced the neovascular tufts area in OIR retina (68.0±6.7% of the control eyes, P<0.05). Even in a high concentration (2mM), betaine never induced any retinal toxicity or cytotoxicity. Betaine significantly inhibited VEGF-induced proliferation, migration, and tube formation in human retinal microvascular endothelial cells (HRMECs). Betaine suppressed VEGF-induced VEGFR-2, Akt and ERK phosphorylation in HRMECs. In human brain astrocytes, betaine reduced tBH-induced ROS production, and subsequently attenuated tBH-induced VEGFA mRNA transcription via suppression of ROS. Our data suggest that betaine has an anti-angiogenic effect on pathologic retinal neovascularization via suppression of ROS mediated VEGF signaling. Betaine could be a potent anti-angiogenic agent to treat pathologic retinal neovascularization. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between human breast milk and retinopathy of prematurity.

PubMed

Fonseca, Luciana Teixeira; Senna, Denise C; Eckert, Gabriela Unchalo; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

2018-04-01

To evaluate the possible protective effect of breast milk against retinopathy of prematurity by comparing the amount of breast milk received by patients who developed retinopathy of prematurity and those who did not and to determine both the required minimum amount of breast milk and the time of life during which neonates need to receive breast milk for this effect to be significant. Cohort study of newborns with a birth weight of <1500 g or gestational age of <32 weeks, or both, born between January 2011 and October 2014 and hospitalized within the first 24 h of life in the Hospital Criança Conceição Neonatal Intensive Care Unit in Porto Alegre, RS, Brazil. The prevalence of retinopathy of prematurity of any degree was 31% (100 of 323 patients) and that of severe retinopathy of prematurity was of 9% (29 of 323 patients). The median amounts of breast milk received daily by patients with and without retinopathy of prematurity were 4.9 mL/kg (interquartile range, 0.3-15.4) and 10.2 mL/kg (1.5-25.5), respectively. The amount of breast milk received in the first 6 weeks of life was inversely associated with the incidence of both retinopathy of prematurity of any degree and severe retinopathy of prematurity in the univariate analyses. However, the statistical significance was maintained only during the sixth week of life in a per-period multivariate analysis controlling for confounding factors. Small amounts of breast milk are inadequate to prevent retinopathy of prematurity in premature newborns at risk for the disease.

Retinopathy of Prematurity: Clinical Features, Classification, Natural History, Management and Outcome.

PubMed

Shah, Parag K; Prabhu, Vishma; Ranjan, Ratnesh; Narendran, Venkatapathy; Kalpana, Narendran

2016-11-07

Retinopathy of prematurity is an avoidable cause of childhood blindness. Proper understanding of the classification and treatment methods is a must in tackling this disease. Literature search with PubMed was conducted covering the period 1940-2015 with regards to retinopathy of prematurity, retrolental fibroplasia, its natural history, classification and treatment. The clinical features, screening and staging of retinopathy of prematurity according to International classification of retinopathy of prematurity (ICROP) has been included with illustrations. The standard current treatment indications, modalities and outcomes from landmark randomized controlled trials on retinopathy of prematurity have been mentioned. This review would help pediatricians to update their current knowledge on classification and treatment of retinopathy of prematurity. Screening for retinopathy of prematurity, in India, should be performed in all preterm neonates who are born <34 weeks gestation and/or <1750 grams birthweight; as well as in babies 34-36 weeks gestation or 1750-2000 grams birthweight if they have risk factors for ROP. Screening should start by one month after birth.

Vibration perception threshold for sight-threatening retinopathy screening in type 2 diabetic outpatients.

PubMed

Shen, Jing; Hu, Yanyun; Liu, Fang; Zeng, Hui; Li, Lianxi; Zhao, Jun; Zhao, Jungong; Zheng, Taishan; Lu, Huijuan; Lu, Fengdi; Bao, Yuqian; Jia, Weiping

2013-10-01

We investigated the relationship between vibration perception threshold and diabetic retinopathy and verified the screening value of vibration perception threshold for severe diabetic retinopathy. A total of 955 patients with type 2 diabetes were recruited and divided into three groups according to their fundus oculi photography results: no diabetic retinopathy (n = 654, 68.48%), non-sight-threatening diabetic retinopathy (n = 189, 19.79%) and sight-threatening diabetic retinopathy (n = 112, 11.73%). Their clinical and biochemical characteristics, vibration perception threshold and the diabetic retinopathy grades were detected and compared. There were significant differences in diabetes duration and blood glucose levels among three groups (all p < 0.05). The values of vibration perception threshold increased with the rising severity of retinopathy, and the vibration perception threshold level of sight-threatening diabetic retinopathy group was significantly higher than both non-sight-threatening diabetic retinopathy and no diabetic retinopathy groups (both p < 0.01). The prevalence of sight-threatening diabetic retinopathy in vibration perception threshold >25 V group was significantly higher than those in 16-24 V group (p < 0.01). The severity of diabetic retinopathy was positively associated with diabetes duration, blood glucose indexes and vibration perception threshold (all p < 0.01). Multiple stepwise regression analysis proved that glycosylated haemoglobin (β = 0.385, p = 0.000), diabetes duration (β = 0.275, p = 0.000) and vibration perception threshold (β = 0.180, p = 0.015) were independent risk factors for diabetic retinopathy. Receiver operating characteristic analysis further revealed that vibration perception threshold higher than 18 V was the optimal cut point for reflecting high risk of sight-threatening diabetic retinopathy (odds ratio = 4.20, 95% confidence interval = 2.67-6.59). There was a close association between vibration perception

Retinopathy of prematurity: an epidemic in the making.

PubMed

Quinn, Graham E; Gilbert, Clare; Darlow, Brian A; Zin, Andrea

2010-10-01

To explore the etiology, incidence and methods to prevent and treat severe retinopathy of prematurity (ROP), which is rapidly becoming a threat to the vision of babies in areas of the world where increasing numbers of premature babies are surviving. The data used in this review were mainly from Medline and PubMed published in English. The search term was "retinopathy of prematurity and premature birth". We discuss the historical perspectives, prevalence and incidence, classification and treatment methods of ROP in premature babies. Peripheral retinal ablation for eyes with severe ROP can help prevent progression to blindness and several large clinical trials have shown the effectiveness of this treatment in high risk eyes. As a greater proportion of VLBW and ELBW babies survive, the population of babies at risk increases. In various regions of the world, different identification criteria are used to determine which babies are at risk of blindness in order to provide timely diagnostic examinations and treatment as needed. Methods for preventing ROP include better ante-natal and obstetric care leading to a reduction in the rate of prematurity, the use of ante-natal corticosteroids, and better neonatal care practices. Recent developments have indicated that management of oxygen supplementation is important for the prevention of severe ROP; however, there is not yet known what oxygen saturation target should be adopted. Sepsis increases severe ROP in very preterm infants. Genetic associations and a telemedicine approach may be explored to detect ROP. Treatment of anti-VEGF therapy are potentially useful in eyes with severe ROP, but long term effects are not yet known and such treatment should be used with great caution. ROP is a potentially binding disease for premature babies which is becoming more prevalent with the development improving neonatal services in many countries in recent years. High priority should be placed on developing approaches to prevent ROP

Sensitivity and specificity of digital retinal imaging for screening diabetic retinopathy.

PubMed

Lopez-Bastida, J; Cabrera-Lopez, F; Serrano-Aguilar, P

2007-04-01

To assess the effectiveness of a non-mydriatic digital camera (45 degrees -30 degrees photographs) compared with the reference method for screening diabetic retinopathy. Type 1 and 2 diabetic patients (n = 773; 1546 eyes) underwent screening for diabetic retinopathy in a prospective observational study. Hospital-based non-mydriatic digital retinal imaging by a consultant specialist in retinal diseases was compared with slit-lamp biomicroscopy and indirect ophthalmoscopy through dilated pupils, as a gold standard, previously performed in a community health centre by another consultant specialist in retinal diseases. The main outcome measures were sensitivity and specificity of screening methods and prevalence of diabetic retinopathy. The prevalence of any form of diabetic retinopathy was 42.4% (n = 328); the prevalence of sight-threatening including macular oedema and proliferative retinopathy was 9.6% (n = 74). Sensitivity of detection of any diabetic retinopathy by digital imaging was 92% (95% confidence interval 90, 94). Specificity of detection of any diabetic retinopathy was 96% (95, 98). The predictive value of the negative tests was 94% and of a positive test 95%. For sight-threatening retinopathy digital imaging had a sensitivity of 100%. A high sensitivity and specificity are essential for an effective screening programme. These results confirm digital retinal imaging with a non-mydriatic camera as an effective option in community-based screening programmes for diabetic retinopathy.

Prolonged Effect of Intensive Therapy on the Risk of Retinopathy Complications in Patients With Type 1 Diabetes Mellitus

PubMed Central

2009-01-01

Objective To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. Methods Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. Results After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P<.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P<.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion The persistent difference in diabetic retinopathy between former intensive and conventional therapy (“metabolic memory”) continues for at least 10 years but may be waning. PMID:19064853

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

Retinopathy in an obesity WHO III cohort: prevalence and risk factors.

PubMed

Mattern, Juri; Lammert, Alexander; Otto, Mirko; Hammes, Hans-Peter

2017-11-01

To assess retinopathy and its risk factors in an obesity WHO III cohort. In the Mannheim Obesity Study , 277 subjects with obesity WHO III aged 18-64 years were examined in a cross-sectional approach. Screening for retinopathy was performed using 3-field retinal photography. Endothelial function was assessed using arteriole-to-venule ratio and flicker light analysis. Subjects with and without retinopathy were analysed for anthropometry, metabolic, vascular and renal parameters. Retinopathy was found in 18 of the 277 subjects (6.5%). Prevalence of retinopathy was 16.7% in subjects with and 3.4% in subjects without diabetes mellitus. Between subjects with and without retinopathy there were significant differences in diabetes prevalence (61.1% vs 21.7%, p<0.001), systolic blood pressure (145.56 vs 131.73 mm Hg, p=0.005), intima-media thickness (0.7 vs 0.59 mm, p=0.034), dilatation of retinal veins in response to flicker light (2.24% vs 4.28%, p=0.004) and creatinine (0.92 vs 0.83 mg/dL, p=0.011). Stepwise logistic regression analysis revealed that the presence of diabetes mellitus led to an 8.3-fold increased risk for retinopathy (OR 8.3, p=0.049, 95% CI 1.01 to 67.49), whereas risk for retinopathy decreased by nearly 50% (OR 0.54, p=0.032, 95% CI 0.30 to 0.95) with each percentage increase in venous dilatation in response to flicker light. Retinopathy prevalence in our obesity WHO III cohort is low. Presence of diabetes mellitus is the most important risk factor for retinopathy. Preserved venular function indicates protection from retinopathy. NCT00770276, Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Production of recombinant protein by a novel oxygen-induced system in Escherichia coli.

PubMed

Baez, Antonino; Majdalani, Nadim; Shiloach, Joseph

2014-04-07

The SoxRS regulon of E. coli is activated in response to elevated dissolved oxygen concentration likely to protect the bacteria from possible oxygen damage. The soxS expression can be increased up to 16 fold, making it a possible candidate for recombinant protein expression. Compared with the existing induction approaches, oxygen induction is advantageous because it does not involve addition or depletion of growth factors or nutrients, addition of chemical inducers or temperature changes that can affect growth and metabolism of the producing bacteria. It also does not affect the composition of the growth medium simplifying the recovery and purification processes. The soxS promoter was cloned into the commercial pGFPmut3.1 plasmid creating pAB49, an expression vector that can be induced by increasing oxygen concentration. The efficiency and the regulatory properties of the soxS promoter were characterized by measuring the GFP expression when the culture dissolved oxygen concentration was increased from 30% to 300% air saturation. The expression level of recombinant GFP was proportional to the oxygen concentration, demonstrating that pAB49 is a controllable expression vector. A possible harmful effect of elevated oxygen concentration on the recombinant product was found to be negligible by determining the protein-carbonyl content and its specific fluorescence. By performing high density growth in modified LB medium, the cells were induced by increasing the oxygen concentration. After 3 hours at 300% air saturation, GFP fluorescence reached 109000 FU (494 mg of GFP/L), representing 3.4% of total protein, and the cell concentration reached 29.1 g/L (DW). Induction of recombinant protein expression by increasing the dissolved oxygen concentration was found to be a simple and efficient alternative expression strategy that excludes the use of chemical, nutrient or thermal inducers that have a potential negative effect on cell growth or the product recovery.

Diabetic retinopathy and its risk factors in patients with type 2 diabetes attending rural primary healthcare facilities in Tamil Nadu.

PubMed

Fredrick, Tony; Kaur, Prabhdeep; Murhekar, Manoj V; Jayaraman, Yuvaraj; Kolandaswamy, K; Rao, Sudha Ramachandra; David, Joseph K

2016-01-01

India has a high burden of diabetic retinopathy ranging from 12.2% to 20.4% among patients with type 2 diabetes mellitus (T2DM). A T2DM management programme was initiated in the public sector in Tamil Nadu. We estimated the prevalence of diabetic retinopathy and its associated risk factors. We did a cross-sectional survey among patients with T2DM attending two primary health centres for treatment and follow-up in Kancheepuram, Tamil Nadu in January- March 2013. We did a questionnaire-based survey, and measured blood pressure and biochemical parameters (serum creatinine, plasma glucose, etc.) of the patients. We examined their eyes by direct and indirect ophthalmoscopy and defined diabetic retinopathy using a modified classification by Klein et al. We calculated the proportion and 95% CI for the prevalence and adjusted odds ratio (AOR) for risk factors associated with diabetic retinopathy. Among the 270 patients, the mean (SD) age was 54.5 (10) years. The median duration of T2DM was 48 months. The prevalence of diabetic retinopathy was 29.6%. Overall, 65.9% of patients had hypertension, 14.4% had nephropathy (eGFR <60 mg/dl) and 67.4% had neuropathy. Among patients with comorbid conditions, 60%, 48%, 32%, and 3% were already diagnosed to have hypertension, neuropathy, retinopathy, and nephropathy, respectively. The risk factors for diabetic retinopathy were hypertension (AOR 3.2, 95% CI 1.7-6.3), duration of T2DM >5 years (AOR 6.5, 95% CI 3.6-11.7), poor glycaemic control (AOR 2.4, 95% CI 1.4-4.4), and nephropathy (AOR 2.3, 95% CI 1.1-4.6). There was a high burden of undetected retinopathy and other comorbid conditions among patients with T2DM. Early detection of comorbid conditions and glycaemic control can be improved by training care-providers and educating patients.

Atmospheric oxygen levels affect mudskipper terrestrial performance: implications for early tetrapods.

PubMed

Jew, Corey J; Wegner, Nicholas C; Yanagitsuru, Yuzo; Tresguerres, Martin; Graham, Jeffrey B

2013-08-01

The Japanese mudskipper (Periophthalmus modestus), an amphibious fish that possesses many respiratory and locomotive specializations for sojourns onto land, was used as a model to study how changing atmospheric oxygen concentrations during the middle and late Paleozoic Era (400-250 million years ago) may have influenced the emergence and subsequent radiation of the first tetrapods. The effects of different atmospheric oxygen concentrations (hyperoxia = 35%, normoxia = 21%, and hypoxia = 7% O2) on terrestrial performance were tested during exercise on a terrestrial treadmill and during recovery from exhaustive exercise. Endurance and elevated post-exercise oxygen consumption (EPOC; the immediate O2 debt repaid post-exercise) correlated with atmospheric oxygen concentration indicating that when additional oxygen is available P. modestus can increase oxygen utilization both during and following exercise. The time required post-exercise for mudskippers to return to a resting metabolic rate did not differ between treatments. However, in normoxia, oxygen consumption increased above hyperoxic values 13-20 h post-exercise suggesting a delayed repayment of the incurred oxygen debt. Finally, following exercise, ventilatory movements associated with buccopharyngeal aerial respiration returned to their rest-like pattern more quickly at higher concentrations of oxygen. Taken together, the results of this study show that P. modestus can exercise longer and recover quicker under higher oxygen concentrations. Similarities between P. modestus and early tetrapods suggest that increasing atmospheric oxygen levels during the middle and late Paleozoic allowed for elevated aerobic capacity and improved terrestrial performance, and likely led to an accelerated diversification and expansion of vertebrate life into the terrestrial biosphere.

Retinal vascular geometry in Asian persons with diabetes and retinopathy.

PubMed

Cheung, Carol Yim-lui; Lamoureux, Ecosse; Ikram, M Kamran; Sasongko, M Bayu; Ding, Jie; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin

2012-05-01

Our purpose was to examine the relationship of retinal vascular parameters with diabetes and retinopathy in an older Asian population. Retinal photographs from participants of a population-based survey of Asian Malay persons aged 40-80 years were analyzed. Specific retinal vascular parameters (tortuosity, branching angle, fractal dimension, and caliber) were measured using a semiautomated computer-based program. Diabetes was defined as random plasma glucose ≥ 11.1 mmol/liter, the use of diabetes medication, or physician-diagnosed diabetes. Retinopathy signs were graded from photographs using the modified Airlie House classification system. A total of 2735 persons were included in the study. Persons with diabetes (n = 594) were more likely to have straighter (less tortuous) arterioles and wider arteriolar and venular caliber than those without diabetes (n = 2141). Among subjects with diabetes, those with retinopathy had wider venular caliber than those without retinopathy (211.3 versus 204.9 mm, p = .001). Among nondiabetic subjects, however, those with retinopathy had more tortuous venules than those without retinopathy [5.19(×10(4)) versus 4.27(×10(4)), p < .001]. Retinal vascular parameters varied by diabetes and retinopathy status in this older Asian cohort. Our findings suggest that subtle alterations in retinal vascular architecture are influenced by diabetes. © 2012 Diabetes Technology Society.

Length of day during early gestation as a predictor of risk for severe retinopathy of prematurity.

PubMed

Yang, Michael B; Rao, Sujata; Copenhagen, David R; Lang, Richard A

2013-12-01

Fetal mice require light exposure in utero during early gestation for normal vascular development in the eye. Because angiogenic abnormalities in retinopathy of prematurity (ROP) are manifested in preterm infants, we investigated whether day length during early gestation was associated with severe ROP (SROP). Single-center, retrospective cohort study. We included a total of 343 premature infants (401-1250 g birth weight [BW], from 1998-2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated. For each infant, average day length (ADL) was calculated during different cumulative time periods and time windows after the estimated date of conception (EDC). Multiple logistic regression analysis (with generalized estimating equations to account for inter-eye correlation) was performed. Association of ADL during early gestation with SROP. In a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational age, multiple births, race, per capita income in the mother's residence ZIP code, and ADL during the first 90 days after the EDC were factors associated with the development of SROP. Each additional hour of ADL (90 days) decreased the likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55-0.94). In a model evaluating the subset of 146 prethreshold ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001; OR, 0.54; 95% CI, 0.37-0.78). Time windows when ADL was most closely associated with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and the prethreshold ROP eyes models, respectively. Higher ADL during early gestation was associated with a lower risk for SROP and may imply a role for prophylactic light treatment during

Emerging climate change signals in the interior ocean oxygen content

NASA Astrophysics Data System (ADS)

Tjiputra, Jerry; Goris, Nadine; Schwinger, Jörg; Lauvset, Siv

2017-04-01

Earth System Models (ESMs) indicate that human-induced climate change will introduce spatially heterogeneous modifications of dissolved oxygen in the North Atlantic. In the upper ocean, an increase (decrease) is predicted at low (high) latitude. Oxygen increase is driven by a reduction of the oxygen consumption for biological remineralization while warming-induced reduction in air-sea fluxes and increase in remineralization due to weaker overturning circulation lead to the projected decrease. In the interior ocean, modifications in the apparent oxygen utilization (AOU) dominate the overall oxygen changes. Moreover, for the southern subpolar gyre, both observations and model hindcast indicate a close relationship between interior ocean oxygen and the subpolar gyre index. Over the 21st century, all ESMs consistently project a steady weakening of this index and consequently the oxygen. Our finding shows that climate change-induced oxygen depletion in the interior has likely occurred and can already be detected. Nevertheless, considering the observational uncertainties, we show that in the proximity of southern subpolar gyre the projected interior trend is sufficiently large enough for early detection.

ADVANCES IN UNDERSTANDING AND MANAGEMENT OF RETINOPATHY OF PREMATURITY

PubMed Central

Hartnett, Mary Elizabeth

2016-01-01

The understanding, diagnosis and treatment of retinopathy of prematurity (ROP) have changed in the last seventy years since the original description of retrolental fibroplasia associated with high oxygenation. It is now recognized that ROP differs in appearance world-wide and as ever smaller and younger premature infants survive. New methods are being evaluated to image the retina, diagnose severe ROP, and determine windows of time for treatment to save eyes and improve visual and neural outcomes. New treatments to promote physiologic retinal vascular development, vascular repair, and inhibit vasoproliferation by regulating proteins involved in vascular endothelial growth factor, insulin-like growth factor, or erythropoietin signaling. Reducing excessive oxidative/nitrosative stress and understanding progenitor cells and neurovascular and glial vascular interactions are being studied. PMID:28012875

Posterior microphthalmos pigmentary retinopathy syndrome.

PubMed

Pehere, Niranjan; Jalali, Subhadra; Deshmukh, Himanshu; Kannabiran, Chitra

2011-04-01

Posterior Microphthalmos Pigmentary Retinopathy Syndrome (PMPRS). Posterior microphthalmos (PM) is a relatively infrequent type of microphthalmos where posterior segment is predominantly affected with normal anterior segment measurements. Herein, we report two siblings with posterior microphthalmos retinopathy syndrome with postulated autosomal recessive mode of inheritance. A 13-year-old child had PM and retinitis pigmentosa (RP) and his 7-year-old sister had PM, RP, and foveoschisis. The genetics of this syndrome and variable phenotype is discussed. Importance of being aware of posterior microphthalmos and its posterior segment associations is highlighted.

Very low doses of heavy oxygen ion radiation induce premature ovarian failure.

PubMed

Mishra, Birendra; Ripperdan, Ryan; Ortiz, Laura; Luderer, Ulrike

2017-08-01

Astronauts are exposed to charged particles during space travel, and charged particles are also used for cancer radiotherapy. Premature ovarian failure is a well-known side effect of conventional, low linear energy transfer (LET) cancer radiotherapy, but little is known about the effects of high LET charged particles on the ovary. We hypothesized that lower LET (16.5 keV/µm) oxygen particles would be less damaging to the ovary than we previously found for iron (LET = 179 keV/µm). Adult female mice were irradiated with 0, 5, 30 or 50 cGy oxygen ions or 50 cGy oxygen plus dietary supplementation with the antioxidant alpha lipoic acid (ALA). Six-hour after irradiation, percentages of ovarian follicles immunopositive for γH2AX, a marker of DNA double strand breaks, 4-HNE, a marker of oxidative lipid damage and BBC3 (PUMA), a proapoptotic BCL-2 family protein, were dose dependently increased in irradiated mice compared to controls. One week after irradiation, numbers of primordial, primary and secondary follicles per ovary were dose dependently decreased, with complete absence of follicles in the 50 cGy groups. The ED 50 for primordial follicle destruction was 4.6 cGy for oxygen compared to 27.5 cGy for iron in our previous study. Serum FSH and LH concentrations were significantly elevated in 50 cGy groups at 8 week. Supplementation with ALA mitigated the early effects, but not the ultimate depletion of ovarian follicles. In conclusion, oxygen charged particles are even more potent inducers of ovarian follicle depletion than charged iron particles, raising concern for premature ovarian failure in astronauts exposed to both particles during space travel. © 2017 Society for Reproduction and Fertility.

Systemic effects of screening for retinopathy of prematurity.

PubMed Central

Laws, D E; Morton, C; Weindling, M; Clark, D

1996-01-01

AIMS: To detect systemic complications of screening for retinopathy of prematurity (ROP), paying particular attention to the physical examination. METHODS: Oxygen saturation, pulse rate, and blood pressure were monitored before, during, and after 110 ROP screening examinations. RESULTS: Following topical mydriatics diastolic blood pressure was elevated by a mean of 6 (SD 7.2) mm Hg. Immediately after the examination there was a further rise in both systolic and diastolic pressure of 4.3 (14.5) mm Hg and 3.3 (11.6) mm Hg, respectively. Oxygen saturation and pulse rate remained stable during the control period and administration of eyedrops. Saturation fell by a median of 3% (95% confidence interval plus or minus 1.2%) after the examination while there was rise in pulse rate of 7 (SD 23.1) beats per minute. This change in pulse rate was not observed in infants on concurrent methylxanthine therapy. No infant had clinically significant changes at the end of the study. CONCLUSION: The initial changes in blood pressure may represent side effects of topical mydriatics but the later changes following the physical examination may be an additional response to the stress of ROP screening. PMID:8695564

Purtscher's retinopathy associated with acute pancreatitis.

PubMed

Hamp, Ania M; Chu, Edward; Slagle, William S; Hamp, Robert C; Joy, Jeffrey T; Morris, Robert W

2014-02-01

Purtscher's retinopathy is a rare condition that is associated with complement-activating systemic diseases such as acute pancreatitis. After pancreatic injury or inflammation, proteases such as trypsin activate the complement system and can potentially cause coagulation and leukoembolization of retinal precapillary arterioles. Specifically, intermediate-sized emboli are sufficiently small enough to pass through larger arteries yet large enough to remain lodged in precapillary arterioles and cause the clinical appearance of Purtscher's retinopathy. This pathology may present with optic nerve edema, impaired visual acuity, visual field loss, as well as retinal findings such as cotton-wool spots, retinal hemorrhage, artery attenuation, venous dilation, and Purtscher flecken. A 57-year-old white man presented with an acute onset of visual field scotomas and decreased visual acuity 1 week after being hospitalized for acute pancreatitis. The retinal examination revealed multiple regions of discrete retinal whitening surrounding the disk, extending through the macula bilaterally, as well as bilateral optic nerve hemorrhages. The patient identified paracentral bilateral visual field defects on Amsler Grid testing, which was confirmed with subsequent Humphrey visual field analysis. Although the patient presented with an atypical underlying etiology, he exhibited classic retinal findings for Purtscher's retinopathy. After 2 months, best corrected visual acuity improved and the retinal whitening was nearly resolved; however, bilateral paracentral visual field defects remained. Purtscher's retinopathy has a distinctive clinical presentation and is typically associated with thoracic trauma but may be a sequela of nontraumatic systemic disease such as acute pancreatitis. Patients diagnosed with acute pancreatitis should have an eye examination to rule out Purtscher's retinopathy. Although visual improvement is possible, patients should be educated that there may be permanent

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; Wei Hsu, Chun; 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

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

Anterior Diabetic Retinopathy Studied by Ultra-widefield Angiography.

PubMed

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

2016-10-01

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. 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. 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). 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.

DNA Methylation-a Potential Source of Mitochondria DNA Base Mismatch in the Development of Diabetic Retinopathy.

PubMed

Mishra, Manish; Kowluru, Renu A

2018-04-21

In the development of diabetic retinopathy, retinal mitochondria are dysfunctional, and mitochondrial DNA (mtDNA) is damaged with increased base mismatches and hypermethylated cytosines. DNA methylation is also a potential source of mutation, and in diabetes, the noncoding region, the displacement loop (D-loop), experiences more methylation and base mismatches than other regions of the mtDNA. Our aim was to investigate a possible crosstalk between mtDNA methylation and base mismatches in the development of diabetic retinopathy. The effect of inhibition of Dnmts (by 5-aza-2'-deoxycytidine or Dnmt1-siRNA) on glucose-induced mtDNA base mismatches was investigated in human retinal endothelial cells by surveyor endonuclease digestion and validated by Sanger sequencing. The role of deamination factors on increased base mismatches was determined in the cells genetically modulated for mitochondrial superoxide dismutase (Sod2) or cytidine-deaminase (APOBEC3A). The results were confirmed in an in vivo model using retinal microvasculature from diabetic mice overexpressing Sod2. Inhibition of DNA methylation, or regulation of cytosine deamination, significantly inhibited an increase in base mismatches at the D-loop and prevented mitochondrial dysfunction. Overexpression of Sod2 in mice also prevented diabetes-induced D-loop hypermethylation and increase in base mismatches. The crosstalk between DNA methylation and base mismatches continued even after termination of hyperglycemia, suggesting its role in the metabolic memory phenomenon associated with the progression of diabetic retinopathy. Inhibition of DNA methylation limits the availability of methylated cytosine for deamination, suggesting a crosstalk between DNA methylation and base mismatches. Thus, regulation of DNA methylation, or its deamination, should impede the development of diabetic retinopathy by preventing formation of base mismatches and mitochondrial dysfunction.

Next-generation sequencing analysis of gene regulation in the rat model of retinopathy of prematurity.

PubMed

Griffith, Rachel M; Li, Hu; Zhang, Nan; Favazza, Tara L; Fulton, Anne B; Hansen, Ronald M; Akula, James D

2013-08-01

The purpose of this study was to identify the genes, biochemical signaling pathways, and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP). Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (Pediatr Res 36:724-731, 1994) oxygen-induced retinopathy model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls. Eight custom-developed pathways with potential relevance to known ROP sequelae were evaluated for significant regulation in ROP: The three major Wnt signaling pathways, canonical, planar cell polarity (PCP), and Wnt/Ca(2+); two signaling pathways mediated by the Rho GTPases RhoA and Cdc42, which are, respectively, thought to intersect with canonical and non-canonical Wnt signaling; nitric oxide signaling pathways mediated by two nitric oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS); and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes was detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes and the NIH's Database for Annotation, Visualization, and Integrated Discovery's GO terms databases. Canonical Wnt signaling was found to be regulated, but the non-canonical PCP and Wnt/Ca(2+) pathways were not. Nitric oxide signaling, as measured by the activation of nNOS and eNOS, was also regulated, as was RA signaling. Biological themes related to protein translation (ribosomes), neural signaling, inflammation and immunity, cell cycle, and cell death were (among others) highly regulated in ROP rats. These several genes and pathways identified by NGS might provide novel targets for intervention in ROP.

Next Generation Sequencing Analysis of Gene Regulation in the Rat Model of Retinopathy of Prematurity

PubMed Central

Griffith, Rachel M.; Li, Hu; Zhang, Nan; Favazza, Tara L.; Fulton, Anne B.; Hansen, Ronald M.; Akula, James D.

2013-01-01

Purpose To identify the genes, biochemical signaling pathways and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP). Methods Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (1994) oxygen-induced retinopathy (OIR) model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls. Eight custom developed pathways with potential relevance to known ROP sequelae were evaluated for significant regulation in ROP: The three major Wnt signaling pathways, canonical, planar cell polarity (PCP), and Wnt/Ca2+, two signaling pathways mediated by the Rho GTPases RhoA and Cdc42, which are respectively thought to intersect with canonical and noncanonical Wnt signaling, nitric oxide signaling pathways mediated by two nitrox oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS), and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes were detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the NIH's Database for Annotation, Visualization and Integrated Discovery (DAVID)'s GO terms databases. Results Canonical Wnt signaling was found to be regulated, but the non-canonical PCP and Wnt/Ca2+ pathways were not. Nitric oxide (NO) signaling, as measured by the activation of nNOS eNOS, was also regulated, as was RA signaling. Biological themes related to protein translation (ribosomes), neural signaling, inflammation and immunity, cell cycle and cell death, were (among others) highly regulated in ROP rats. Conclusions These several genes and pathways identified by NGS might provide novel targets for intervention in ROP. PMID:23775346

Targeting Neovascularization in Ischemic Retinopathy: Recent Advances

PubMed Central

Al-Shabrawey, Mohamed; Elsherbiny, Mohamed; Nussbaum, Julian; Othman, Amira; Megyerdi, Sylvia; Tawfik, Amany

2014-01-01

Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities. PMID:25598837

Oxygen reservoirs in the early solar nebula inferred from an Allende CAI.

PubMed

Young, E D; Russell, S S

1998-10-16

Ultraviolet laser microprobe analyses of a calcium-aluminum-rich inclusion (CAI) from the Allende meteorite suggest that a line with a slope of exactly 1.00 on a plot of delta (17)O against delta (18)O represents the primitive oxygen isotope reservoir of the early solar nebula. Most meteorites are enriched in (17)O and (18)O relative to this line, and their oxygen isotope ratios can be explained by mass fractionation or isotope exchange initiating from the primitive reservoir. These data establish a link between the oxygen isotopic composition of the abundant ordinary chondrites and the primitive (16)O-rich component of CAIs.

Oxygen reservoirs in the early solar nebula inferred from an allende CAI

PubMed

Young; Russell

1998-10-16

Ultraviolet laser microprobe analyses of a calcium-aluminum-rich inclusion (CAI) from the Allende meteorite suggest that a line with a slope of exactly 1.00 on a plot of delta17O against delta18O represents the primitive oxygen isotope reservoir of the early solar nebula. Most meteorites are enriched in 17O and 18O relative to this line, and their oxygen isotope ratios can be explained by mass fractionation or isotope exchange initiating from the primitive reservoir. These data establish a link between the oxygen isotopic composition of the abundant ordinary chondrites and the primitive 16O-rich component of CAIs.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

PubMed Central

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

Risk of Radiation Retinopathy in Patients With Orbital and Ocular Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaushik, Megha; Pulido, Jose S.; Schild, Steven E.

2012-12-01

Purpose: Radiation retinopathy is a potential long-term complication of radiation therapy to the orbit. The risk of developing this adverse effect is dose dependent; however, the threshold is unclear. The aim of this study was to identify the risk of developing radiation retinopathy at increasing radiation doses. Methods and Materials: A 40-year retrospective review was performed of patients who received external beam radiation therapy for ocular/orbital non-Hodgkin lymphoma (NHL). Results: Sixty-seven patients who had at least one ophthalmic follow-up examination were included in this study. Most patients (52%) were diagnosed with NHL involving the orbit. Patients received external beam radiationmore » therapy at doses between 1886 and 5400 cGy (mean, 3033 {+-} 782 cGy). Radiation retinopathy developed in 12% of patients, and the median time to diagnosis was 27 months (range, 15-241months). The mean prescribed radiation dose in patients with retinopathy was 3309 {+-} 585 cGy, and the estimated retinal dose (derived by reviewing the dosimetry) was 3087 {+-} 1030 cGy. The incidence of retinopathy increased with dose. The average prescribed daily fractionated dose was higher in patients who developed retinopathy than in patients who did not (mean, 202 cGy vs 180 cGy, respectively; P = .04). More patients with radiation retinopathy had comorbid diabetes mellitus type 2 than patients without retinopathy (P = .015). In our study, the mean visual acuity of the eyes that received radiation was worse than that of the eyes that did not (P = .027). Other postradiotherapy ocular findings included keratitis (6%), dry eyes (39%), and cataract (33%). Conclusions: Radiation retinopathy, a known complication of radiotherapy for orbital tumors, relates to vascular comorbidities and dose. Higher total doses and larger daily fractions (>180 cGy) appear to be related to higher rates of retinopathy. Future larger studies are required to identify a statistically significant threshold

The role of retinopathy distribution and other lesion types for the definition of examination intervals during screening for diabetic retinopathy.

PubMed

Ometto, Giovanni; Erlandsen, Mogens; Hunter, Andrew; Bek, Toke

2017-06-01

It has previously been shown that the intervals between screening examinations for diabetic retinopathy can be optimized by including individual risk factors for the development of the disease in the risk assessment. However, in some cases, the risk model calculating the screening interval may recommend a different interval than an experienced clinician. The purpose of this study was to evaluate the influence of factors unrelated to diabetic retinopathy and the distribution of lesions for discrepancies between decisions made by the clinician and the risk model. Therefore, fundus photographs from 90 screening examinations where the recommendations of the clinician and a risk model had been discrepant were evaluated. Forty features were defined to describe the type and location of the lesions, and classification and ranking techniques were used to assess whether the features could predict the discrepancy between the grader and the risk model. Suspicion of tumours, retinal degeneration and vascular diseases other than diabetic retinopathy could explain why the clinician recommended shorter examination intervals than the model. Additionally, the regional distribution of microaneurysms/dot haemorrhages was important for defining a photograph as belonging to the group where both the clinician and the risk model had recommended a short screening interval as opposed to the other decision alternatives. Features unrelated to diabetic retinopathy and the regional distribution of retinal lesions may affect the recommendation of the examination interval during screening for diabetic retinopathy. The development of automated computerized algorithms for extracting information about the type and location of retinal lesions could be expected to further optimize examination intervals during screening for diabetic retinopathy. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Screening Intervals for Diabetic Retinopathy and Implications for Care.

PubMed

Scanlon, Peter H

2017-09-05

The purpose of this study is to review the evidence that lower risk groups who could safely be screened less frequently for sight-threatening diabetic retinopathy (DR) than annually. Data have demonstrated that people with no DR in either eye are at a low risk of progression to sight-threatening DR over a 2-year period (event rate 4.8 per 1000 person years), irrespective of whether the screening method is one-field non-mydriatic or two-field mydriatic digital photography. Low risk has been defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with risk factor data. The risk of an extension to 2 years is less than 5 per 1000 person years in a population with a national screening programme, and the general standard of diabetes care is relatively good, whether low risk is defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with other risk factor data. The definition used in different populations is likely to depend on the availability of data.

Computer-based detection of diabetes retinopathy stages using digital fundus images.

PubMed

Acharya, U R; Lim, C M; Ng, E Y K; Chee, C; Tamura, T

2009-07-01

Diabetes mellitus is a heterogeneous clinical syndrome characterized by hyperglycaemia and the long-term complications are retinopathy, neuropathy, nephropathy, and cardiomyopathy. It is a leading cause of blindness. Diabetic retinopathy is the progressive pathological alterations in the retinal microvasculature, leading to areas of retinal nonperfusion, increased vascular permeability, and the pathological proliferation of retinal vessels. Hence, it is beneficial to have regular cost-effective eye screening for diabetes subjects. Nowadays, different stages of diabetes retinopathy are detected by retinal examination using indirect biomicroscopy by senior ophthalmologists. In this work, morphological image processing and support vector machine (SVM) techniques were used for the automatic diagnosis of eye health. In this study, 331 fundus images were analysed. Five groups were identified: normal retina, mild non-proliferative diabetic retinopathy, moderate non-proliferative diabetic retinopathy, severe non-proliferative diabetic retinopathy, and proliferative diabetic retinopathy. Four salient features blood vessels, microaneurysms, exudates, and haemorrhages were extracted from the raw images using image-processing techniques and fed to the SVM for classification. A sensitivity of more than 82 per cent and specificity of 86 per cent was demonstrated for the system developed.

Incidence of retinopathy in chronic hepatitis C patients treated with pegylated interferon alpha 2a and ribavirin combination therapy.

PubMed

Kashif, Muhammad; Saleem, Muhammad Khurram; Farooka, Imran Khan; Husnain, Amina; Siddiqui, Arif Mahmood

2015-01-01

The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss.

Retinal micropseudocysts in diabetic retinopathy: prospective functional and anatomic evaluation.

PubMed

Forte, Raimondo; Cennamo, Gilda; Finelli, Maria Luisa; Bonavolontà, Paola; Greco, Giovanni Maria; de Crecchio, Giuseppe

2012-01-01

To evaluate the prevalence, progression and functional predictive value of retinal micropseudocysts (MPCs) in diabetic patients. Prospective controlled observational study. From among all the type 2 diabetic patients evaluated during a period of 5 months between September 2009 and January 2010, we enrolled all patients with retinal MPCs at spectral-domain scanning laser ophthalmoscope/optical coherence tomography (SD-SLO/OCT) not previously treated for diabetic retinopathy. Forty diabetic patients without MPCs served as the control group. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular sensitivity and stability of fixation at SD-SLO/OCT microperimetry were measured monthly for 12 months. 22/156 patients with type 2 diabetes (14.1%, 32 eyes) met the inclusion criteria. The 95% confidence interval for the prevalence estimate of MPCs was 12.3-16.6%. Mean BCVA, CRT and central retinal sensitivity at baseline were 77.53 ± 2.2 Early Treatment Diabetic Retinopathy Study letters, 242.31 ± 31.0 µm and 15.95 ± 0.61 dB, respectively. Fixation was stable in all cases. Compared to the control group, eyes with MPCs had similar BCVA but greater CRT (p = 0.01) and reduced macular sensitivity (p = 0.001) at baseline and at each follow-up visit. Over time, CRT remained stable in eyes with MPCs, whereas macular sensitivity progressively decreased. MPCs in diabetic retinopathy are associated, temporally or causally, with a progressive reduction of macular sensitivity despite a stable BCVA, CRT and fixation. Copyright © 2011 S. Karger AG, Basel.

Digital Tracking and Control of Retinal Images

DTIC Science & Technology

1993-01-01

induced retinal lesions are used to treat a variety of eye diseases such as diabetic retinopathy and retinal tears or breaks. Both the location and...one second and typical treatment for a disease such as diabetic retinopathy requires as many as 2000 lesions per eye. This type of tedious task is...Oxygenation and Laser Treatment in Patients with Diabetic Retinopathy ", American Journal of Ophthalmology, Volume 113, January 1992, pp 36 - 38. [21

A Review on Recent Developments for Detection of Diabetic Retinopathy.

PubMed

Amin, Javeria; Sharif, Muhammad; Yasmin, Mussarat

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.

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

Endothelium dysfunction markers in patients with diabetic retinopathy.

PubMed

Siemianowicz, Krzysztof; Francuz, Tomasz; Gminski, Jan; Telega, Alicja; Syzdól, Marcin

2005-03-01

Diabetes mellitus leads to endothelium dysfunction and an accelerated progression of atherosclerosis. Vascular complications of diabetes mellitus can affect not only large and medium arteries resulting in coronary heart disease and peripheral arteries diseases, but also small vessels leading to retinopathy and nephropathy. Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin and von Willebrand factor (vWF) are considered as markers of endothelium dysfunction. The aim of our study was to evaluate plasma levels of ICAM-1, VCAM-1, E-selectin and vWF in patients with type 2 diabetes mellitus receiving insulin therapy and who had diabetic non-proliferative retinopathy, proliferative retinopathy, or did not develop diabetic retinopathy. There were no statistically significant differences between studied groups in any of evaluated endothelium dysfunction markers. There was no statistically significant correlation between measured parameters and a period of diabetic history. None of the studied markers presented a significant correlation with a period of insulin treatment.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Jiangchun; Wang, Ruobing; Ye, Zhouheng

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-1βmore » (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. - Highlights: • Methane exerts protective effect on diabetic retinopathy via anti-inflammation. • Therapeutic effect of

Redox-Triggered Bonding-Induced Emission of Thiol-Functionalized Gold Nanoclusters for Luminescence Turn-On Detection of Molecular Oxygen.

PubMed

Ao, Hang; Feng, Hui; Zhao, Mengting; Zhao, Meizhi; Chen, Jianrong; Qian, Zhaosheng

2017-11-22

Most optical sensors for molecular oxygen were developed based on the quenching effect of the luminescence of oxygen-sensitive probes; however, the signal turn-off mode of these probes is undesirable to quantify and visualize molecular oxygen. Herein, we report a novel luminescence turn-on detection strategy for molecular oxygen via the specific oxygen-triggered bonding-induced emission of thiol-functionalized gold nanoclusters. Thiol-functionalized gold nanoclusters were prepared by a facile one-step synthesis, and as-prepared gold nanoclusters possess significant aggregation-induced emission (AIE) property. It is the first time to discover the oxygen-triggered bonding-induced emission (BIE) behavior of gold nanoclusters, which results in disulfide-linked covalent bonding assemblies with intensely red luminescence. This specific redox-triggered BIE is capable of quantitatively detecting dissolved oxygen in aqueous solution in a light-up manner, and trace amount of dissolved oxygen at ppb level is achieved based on this detection method. A facile and convenient test strip for oxygen detection was also developed to monitor molecular oxygen in a gas matrix. Covalent bonding-induced emission is proven to be a more efficient way to attain high brightness of AIEgens than a physical aggregation-induced emission process, and provides a more convenient and desirable detection method for molecular oxygen than the previous sensors.

Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

PubMed

Zhu, Su-Hua; Liu, Bing-Qian; Hao, Mao-Juan; Fan, Yi-Xin; Qian, Cheng; Teng, Peng; Zhou, Xiao-Wei; Hu, Liang; Liu, Wen-Tao; Yuan, Zhi-Lan; Li, Qing-Ping

2017-10-01

Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1β expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

TPL2 (Therapeutic Targeting Tumor Progression Locus-2)/ATF4 (Activating Transcription Factor-4)/SDF1α (Chemokine Stromal Cell-Derived Factor-α) Axis Suppresses Diabetic Retinopathy.

PubMed

Lai, De-Wei; Lin, Keng-Hung; Sheu, Wayne Huey-Herng; Lee, Maw-Rong; Chen, Chung-Yu; Lee, Wen-Jane; Hung, Yi-Wen; Shen, Chin-Chang; Chung, Tsung-Ju; Liu, Shing-Hwa; Sheu, Meei-Ling

2017-09-01

Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of N ε -(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. Serum N ε -(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between N ε -(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell-derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). This study demonstrates that inhibiting the N ε -(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus-mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema. © 2017

ND:YAG laser for preretinal hemorrhage in diabetic retinopathy.

PubMed

Karagiannis, Dimitrios; Kontadakis, Georgios A; Flanagan, Declan

2018-06-01

To present fundus images of a case with severe preretinal hemorrhage in diabetic retinopathy that was treated with posterior hyaloidotomy with an Nd:YAG laser. A 35-year-old diabetic patient presented with sudden painless loss of vision due to severe preretinal hemorrhage over the macular area and high risk proliferative diabetic retinopathy. Her visual acuity was counting fingers. Posterior hyaloid face was treated with Nd:YAG laser (posterior hyaloidotomy). Panretinal laser photocoagulation was first performed to control the proliferative diabetic retinopathy. Blood drained inferiorly into the vitreous cavity with clearance of the premacular area. Prompt treatment with Panretinal laser photocoagulation followed by posterior hyaloidotomy with the YAG laser is a viable option in order to avoid further proliferative diabetic retinopathy complications and vision loss. The current image clearly depicts treatment efficacy.

Reactive oxygen species production, induced by atmospheric modification, alter conidial quality of Beauveria bassiana.

PubMed

Pérez-Guzmán, D; Montesinos-Matías, R; Arce-Cervantes, O; Gómez-Quiroz, L E; Loera, O; Garza-López, P M

2016-08-01

The aim of this study was to determine the relationship between reactive oxygen species (ROS) production and conidial infectivity in Beauveria bassiana. Beauveria bassiana Bb 882.5 was cultured in solid-state culture (SSC) using rice under three oxygen conditions (21%, or pulses at 16 and 26%). Hydrophobicity was determined using exclusion phase assay. Bioassays with larvae or adults of Tenebrio molitor allowed the measurements of infectivity parameters. A fluorometric method was used for ROS quantification (superoxide and total peroxides). NADPH oxidase (NOX) activity was determined by specific inhibition. Conidial hydrophobicity decreased by O2 pulses. Mortality of larvae was only achieved with conidia harvested from cultures under 21% O2 ; whereas for adult insects, the infectivity parameters deteriorated in conidia obtained after pulses at 16 and 26% O2 . At day 7, ROS production increased after 16 and 26% O2 treatments. NOX activity induced ROS production at early stages of the culture. Modification of atmospheric oxygen increases ROS production, reducing conidial quality and infectivity. This is the first study in which conidial infectivity and ROS production in B. bassiana has been related, enhancing the knowledge of the effect of O2 pulses in B. bassiana. © 2016 The Society for Applied Microbiology.

Retinal vascular geometry and 6 year incidence and progression of diabetic retinopathy.

PubMed

Cheung, Carol Yim-Lui; Sabanayagam, Charumathi; Law, Antony Kwan-Pui; Kumari, Neelam; Ting, Daniel Shu-Wei; Tan, Gavin; Mitchell, Paul; Cheng, Ching Yu; Wong, Tien Yin

2017-09-01

We aimed to examine prospectively the association between a range of retinal vascular geometric variables measured from retinal photographs and the 6 year incidence and progression of diabetic retinopathy. We conducted a prospective, population-based cohort study of Asian Malay individuals aged 40-80 years at baseline (n = 3280) who returned for a 6 year follow-up. Retinal vascular geometric variables (tortuosity, branching, fractal dimension, calibre) were measured from baseline retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Diabetic retinopathy was graded from baseline and follow-up photographs using the modified Airlie House classification system. Incidence of diabetic retinopathy was defined as a severity of ≥15 at follow-up among those without diabetic retinopathy at baseline. Incidence of referable diabetic retinopathy was defined as moderate or severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or diabetic macular oedema at follow-up in participants who had had no or mild non-proliferative diabetic retinopathy at baseline. Progression of diabetic retinopathy was defined as an increase in severity of ≥2 steps at follow-up. Log-binomial models with an expectation-maximisation algorithm were used to estimate RR adjusting for age, sex, diabetes duration, HbA 1c level, BP, BMI, estimated GFR and total and HDL-cholesterol at baseline. A total of 427 individuals with diabetes participated in the baseline and 6 year follow-up examinations. Of these, 19.2%, 7.57% and 19.2% developed incidence of diabetic retinopathy, incidence of referable diabetic retinopathy and diabetic retinopathy progression, respectively. After multivariate adjustment, greater arteriolar simple tortuosity (mean RR [95% CI], 1.34 [1.04, 1.74]), larger venular branching angle (RR 1.26 [1.00, 1.59]) and larger venular branching coefficient (RR 1.26 [1.03, 1.56]) were associated with incidence of diabetic retinopathy

Diabetic Retinopathy in a Multi-ethnic Cohort in the United States

PubMed Central

WONG, TIEN YIN; KLEIN, RONALD; ISLAM, F.M. AMIRUL; COTCH, MARY FRANCES; FOLSOM, AARON R.; KLEIN, BARBARA E.K.; SHARRETT, A. RICHEY; SHEA, STEVEN

2008-01-01

PURPOSE To describe the prevalence and risk factors of diabetic retinopathy in a multi-ethnic US population of whites, blacks, hispanics, and chinese. DESIGN Cross-sectional study of 778 individuals from ages 45 to 85 years with diabetes, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS Retinal photographs were obtained with a 45° nonmydriatic digital fundus camera. Presence and severity of diabetic retinopathy were graded at a central reading center on the basis of a modification of the Airlie House classification system. All participants underwent a standardized interview, examination, and laboratory investigations. RESULTS In this population with diabetes, the prevalence of any retinopathy was 33.2% and macular edema 9.0%. The prevalence of any diabetic retinopathy and macular edema was significantly higher in blacks (36.7% and 11.1%) and hispanics (37.4% and 10.7%) than in whites (24.8% and 2.7%) and chinese (25.7% and 8.9%) (P = .01 and P = .007, comparing racial/ethnic differences for retinopathy and macular edema, respectively). Significant independent predictors of any retinopathy were longer duration of diabetes, higher fasting serum glucose, use of diabetic oral medication or insulin, and greater waist-hip ratio. Race was not an independent predictor of any retinopathy. CONCLUSIONS This study provides contemporary data on the prevalence of and risk factors for diabetic retinopathy among whites, blacks, hispanics, and chinese participating in the MESA. PMID:16490489

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

Retinopathy of prematurity in Indonesia: Incidence and risk factors.

PubMed

Edy Siswanto, J; Sauer, Pieter Jj

2017-01-01

Retinopathy of prematurity (ROP) is a vaso-proliferative disease of the eye, which mainly affects preterm newborn infants with an incompletely vascularized retina. The incidence of ROP has increased in industrialized countries due to the increased survival of extremely low birth weight (ELBW) infants. ROP is also increasing in developing countries like Indonesia, where it is most likely due to the improved survival of ELBW infants. To ascertain the incidence of ROP and possible risk factors associated with the development of ROP in preterm infants in Indonesia. We reviewed the literature on the incidence and potential risk factors for the development of ROP in Indonesia, obtained data from three referral eye clinics and added data from our institution. The reported incidence of all stages of ROP in infants with a gestational age of <32 weeks ranged from 18-30%. One study showed that ROP also occurred at older gestational ages. Blindness due to ROP was seen in infants up to 35 weeks and with a birth weight of 2000 g. Retinopathy of prematurity is an important cause of ocular morbidity and blindness in Indonesia. The overall incidence of ROP in infants born below 32 weeks in Indonesia is higher than in developed countries, and it is seen in infants with older gestational ages. This might be due to a less strict monitoring during the use of oxygen in Indonesia compared to industrialized countries.

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

PubMed

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

2016-01-01

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

Early Oxygen-Utilization and Brain Activity in Preterm Infants

PubMed Central

de Vries, Linda S.; Groenendaal, Floris; Toet, Mona C.; Lemmers, Petra M. A.; Vosse van de, Renè E.; van Bel, Frank; Benders, Manon J. N. L.

2015-01-01

The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in μV (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants. PMID:25965343

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

PubMed Central

Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

2011-01-01

BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

Assessing Progress in Retinopathy Outcomes in Type 1 Diabetes

PubMed Central

LeCaire, Tamara J.; Palta, Mari; Klein, Ronald; Klein, Barbara E.K.; Cruickshanks, Karen J.

2013-01-01

OBJECTIVE The Wisconsin Diabetes Registry Study (WDRS) cohort consisted of patients diagnosed with type 1 diabetes in the same geographic region as, but 8–34 years later than the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) cohort, providing a unique opportunity to assess changes in complications. We estimated the current prevalence and severity of diabetic retinopathy at 20 years of diabetes duration, compared these between eras, and evaluated the influence of diabetes management. RESEARCH DESIGN AND METHODS Twenty-year examinations, including fundus photographs, were completed on 305 WDRS subjects during 2007–2011. A subgroup of the WESDR cohort participated in one of four study visits during 1980–1996, at similar diabetes duration (n = 583). Adjusted ordinal logistic regression with three retinopathy severity categories was used to estimate odds ratios (ORs) of more severe retinopathy with diagnosis during an earlier era. RESULTS Mean hemoglobin A1c (HbA1c) was lower in WDRS than in WESDR (8.0% vs. 9.3% [P < 0.001], and 93.4% vs. 21.3% [P < 0.001]) used ≥3 daily insulin injections or an insulin pump. In WDRS, 18% had vision-threatening levels of retinopathy vs. 43% in WESDR. The adjusted OR of more severe retinopathy in the earlier era (OR 3.0 [95% CI 2.2–4.0]) was reduced by including 20-year HbA1c in the model (OR 2.2 [1.6–3.0]). CONCLUSIONS Retinopathy severity at a diabetes duration of 20 years is lower in the more recent era of type 1 diabetes. Updated projections should be used when informing newly diagnosed individuals of prognosis and for health care cost assessments. Current glycemic control explained a limited amount of the difference. PMID:23193204

Prevalence of blindness and diabetic retinopathy in northern Jordan.

PubMed

Rabiu, Mansur M; Al Bdour, Muawyah D; Abu Ameerh, Mohammed A; Jadoon, Muhammed Z

2015-01-01

To estimate the prevalence of blindness, visual impairment, diabetes, and diabetic retinopathy in north Jordan (Irbid) using the rapid assessment of avoidable blindness and diabetic retinopathy methodology. A multistage cluster random sampling technique was used to select participants for this survey. A total of 108 clusters were selected using probability proportional to size method while subjects within the clusters were selected using compact segment method. Survey teams moved from house to house in selected segments examining residents 50 years and older until 35 participants were recruited. All eligible people underwent a standardized examination protocol, which included ophthalmic examination and random blood sugar test using digital glucometers (Accu-Chek) in their homes. Diabetic retinopathy among diabetic patients was assessed through dilated fundus examination. A total of 3638 out of the 3780 eligible participants were examined. Age- and sex-adjusted prevalence of blindness, severe visual impairment, and visual impairment with available correction were 1.33% (95% confidence interval [CI] 0.87-1.73), 1.82% (95% CI 1.35-2.25), and 9.49% (95% CI 8.26-10.74), respectively, all higher in women. Untreated cataract and diabetic retinopathy were the major causes of blindness, accounting for 46.7% and 33.2% of total blindness cases, respectively. Glaucoma was the third major cause, accounting for 8.9% of cases. The prevalence of diabetes mellitus was 28.6% (95% CI 26.9-30.3) among the study population and higher in women. The prevalence of any retinopathy among diabetic patients was 48.4%. Cataract and diabetic retinopathy are the 2 major causes of blindness and visual impairment in northern Jordan. For both conditions, women are primarily affected, suggesting possible limitations to access to services. A diabetic retinopathy screening program needs to proactively create sex-sensitive awareness and provide easily accessible screening services with prompt treatment.

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

PubMed Central

Abcouwer, Steven F.; Gardner, Thomas W.

2014-01-01

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

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production

PubMed Central

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis. Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis. More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress. PMID:27899933

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production.

PubMed

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis . Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis . More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress.

Low oxygen tension enhances endothelial fate of human pluripotent stem cells.

PubMed

Kusuma, Sravanti; Peijnenburg, Elizabeth; Patel, Parth; Gerecht, Sharon

2014-04-01

A critical regulator of the developing or regenerating vasculature is low oxygen tension. Precise elucidation of the role of low oxygen environments on endothelial commitment from human pluripotent stem cells necessitates controlled in vitro differentiation environments. We used a feeder-free, 2-dimensional differentiation system in which we could monitor accurately dissolved oxygen levels during human pluripotent stem cell differentiation toward early vascular cells (EVCs). We found that oxygen uptake rate of differentiating human pluripotent stem cells is lower in 5% O2 compared with atmospheric conditions. EVCs differentiated in 5% O2 had an increased vascular endothelial cadherin expression with clusters of vascular endothelial cadherin+ cells surrounded by platelet-derived growth factor β+ cells. When we assessed the temporal effects of low oxygen differentiation environments, we determined that low oxygen environments during the early stages of EVC differentiation enhance endothelial lineage commitment. EVCs differentiated in 5% O2 exhibited an increased expression of vascular endothelial cadherin and CD31 along with their localization to the membrane, enhanced lectin binding and acetylated low-density lipoprotein uptake, rapid cord-like structure formation, and increased expression of arterial endothelial cell markers. Inhibition of reactive oxygen species generation during the early stages of differentiation abrogated the endothelial inductive effects of the low oxygen environments. Low oxygen tension during early stages of EVC derivation induces endothelial commitment and maturation through the accumulation of reactive oxygen species, highlighting the importance of regulating oxygen tensions during human pluripotent stem cell-vascular differentiation.

Lack of Screening Underlies Most Stage-5 Retinopathy of Prematurity among Cases Presenting to a Tertiary Eye Center in India.

PubMed

Azad, Rajvardhan; Chandra, Parijat; Gangwe, Anil; Kumar, Vivek

2016-11-07

To study the barriers to effective screening, early detection and treatment of Retinopathy of Prematurity leading to advanced disease. Cross-sectional study. Tertiary eye care hospital in northern India. 115 babies with bilateral stage 5 ROP identified amongst 354 preterm infants examined over a one year period. Information regarding gestational age, birthweight, duration of stay in nursery, duration of supplemental oxygen therapy and treatment details were obtained from discharge summary when available, and by interviewing carers.28 stage 5 ROP eyes underwent pars plana lensectomy and vitrectomy. Among the 354 infants (708 eyes) examined, 115 had stage 5 ROP in both eyes. The mean post conceptional age (PCA) at first visit to an ophthalmologist was 54.6 (7.6) weeks (Median 52.9 ± 4.2). The mean overall delay in first examination for Retinopathy of Prematurity was 24.7 (3.9) weeks. Most common risk factor was oxygen therapy in 103 babies (89.6%). 109 (89.8%) babies had never been screened for ROP; four babies fell outside the NNF guidelines (i.e. they had a birth weight of 1750 gms or more and were born at 34 weeks gestational age or more). Another important finding is that only 4.3% of babies were given the correct diagnosis. While 99 babies (86.1%) were referred by ophthalmologists, only 10 babies (8.7%) were referred by pediatricians. A large number were from the capital city of Delhi (21 babies, 18.2%). 28 stage 5 ROP eyes (12.1%) underwent surgery, and at 6 months follow up, only 20 operated eyes had visible attached posterior pole. 210 (91.3%) stage 5 eyes were irreversibly blind. ROP is an increasingly important cause of leucocoria. There were notable gaps in timely ROP screening, referral and treatment and much needs to be done to improve awareness amongst ophthalmologists about ROP. Measures are needed to improve the coverage of initiatives for the detection and timely treatment of sight threatening ROP in India as well as improving neonatal care to

Incidence of retinopathy in chronic hepatitis C patients treated with pegylated interferon alpha 2a and ribavirin combination therapy

PubMed Central

Kashif, Muhammad; Saleem, Muhammad Khurram; Farooka, Imran Khan; Husnain, Amina; Siddiqui, Arif Mahmood

2015-01-01

Objectives: The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. Methods: This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. Results: One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. Conclusion: Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss. PMID:25878638

Hydrogen peroxide and the evolution of oxygenic photosynthesis

NASA Technical Reports Server (NTRS)

Mckay, C. P.; Hartman, H.

1991-01-01

Possible pathways for the evolution of oxygenic photosynthesis in the early reducing atmosphere of the earth are discussed. It is suggested that the abiotic production of atmospheric oxidants could have provided a mechanism by which locally oxidizing conditions were sustained within spatially confined habitats thus removing the available reductants and forcing photosynthetic organisms to utilize water (rather than ferrous or sulfide ions) as the electron donor. It is argued that atmospheric H2O2 played the key role in inducing oxygenic photosynthesis, because, as peroxide concentrations local environments increased, primitive organisms would not only be faced with a loss of a reductant, but would be also forced to develop a biochemical apparatus (such as catalase) that would protect them against the products of oxygenic photosynthesis. This scenario allows for the early evolution of oxygenic photosynthesis at the time when global conditions were still anaerobic.

Using Triple Oxygen Isotope Analyses of Biogenic Carbonate to Reconstruct Early Triassic Ocean Oxygen Isotopic Values and Temperatures

NASA Astrophysics Data System (ADS)

Gibbons, J. A.; Sharp, Z. D.; Atudorei, V.

2017-12-01

The calcite-water triple oxygen isotope fractionation is used to determine isotopic equilibrium and ancient ocean oxygen isotopic values and temperatures. Unlike conventional δ18O analysis where the formation water's isotopic value is assumed, paired δ17O-δ18O measurements allow for the water's isotopic composition to be calculated because there is only one unique solution for equilibrium fractionation using Δ17O-δ18O values (where Δ17O=δ17O-0.528δ18O). To a first approximation, the calcite-water equilibrium fractionation factor, θ (where θ=ln17α/ln18α), varies with temperature by 0.00001/°. The calcite-water equilibrium fractionation line was determined at two temperatures, 30° and 0°, by using modern carbonate samples that formed in ocean water with a δ18O value of 0‰. The θ values for the 30° and 0° samples are 0.52515 and 0.52486, respectively. Oxygen values were measured using complete fluorination in nickel tubes with BrF5 as the reaction reagent. We calibrated all oxygen values to the SMOW-SLAP scale by measuring SMOW, SLAP, San Carlos olivine, NBS-18, NBS-19, and PDB. The triple oxygen isotope calcite-water equilibrium fractionation line was applied to well preserved Early Triassic ammonite shells from the Western United States. Based on paired δ17O-δ18O measurements, the samples did not form in equilibrium with an ice-free ocean with an oxygen isotopic value of -1‰ or the modern ocean value of 0‰. Assuming the calcite is still primary and formed in equilibrium with the ocean water, our data indicate that the δ18O value of the ocean in the early Triassic was 3-5‰ lower than modern. Samples from the Smithian thermal maximum formed in water 10° warmer than samples from after the thermal maximum. Paired δ17O-δ18O measurements of pristine ancient carbonates may provide a better understanding of past ocean conditions during climate change events.

Astigmatism Progression in the Early Treatment for Retinopathy of Prematurity Study to 6 years of age

PubMed Central

Davitt, Bradley V.; Quinn, Graham E.; Wallace, David K.; Dobson, Velma; Hardy, Robert J.; Tung, Betty; Lai, Dejian; Good, William V.

2011-01-01

Purpose To examine the prevalence of astigmatism (≥1.00 diopter (D)) and high astigmatism (≥2.00 D) from 6 months post term due date to 6 years postnatal, in preterm children with birth weight ≤ 1251g who developed high-risk prethreshold retinopathy of prematurity (ROP) and participated in the Early Treatment for ROP (ETROP) Study. Design Observational Cohort Study Participants 401 infants who developed high-risk prethreshold ROP in one or both eyes and were randomized to early treatment (ET) versus conventional management (CM). Refractive error was measured by cycloplegic retinoscopy. Eyes were excluded if they received additional retinal, glaucoma, or cataract surgery. Intervention Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP or to receive treatment only if threshold ROP developed. Main Outcome Measures Astigmatism and high astigmatism at each study visit. Results For both ET and CM eyes, there was a consistent increase in prevalence of astigmatism over time, increasing from 42% at 4 years to 52% by 6 years for the group of ET eyes and from 47% to 54% in the CM eyes. There was no statistically significant difference between the slopes (rate of change per month) of the ET and CM eyes for both astigmatism and high astigmatism. (P=0.75) Conclusions By 6 years of age, over 50% of eyes with high-risk prethreshold ROP developed astigmatism ≥ 1.00 D, and nearly 25% of such eyes had high astigmatism (≥ 2.00 D). Presence of astigmatism was not influenced by timing of treatment, zone of acute-phase ROP, or presence of plus disease. However, there was a trend toward higher prevalence of astigmatism and high astigmatism in eyes with ROP residua. Most astigmatism was with-the-rule (75º –105º). More eyes with Type 2 than Type 1 had astigmatism by 6 years. These findings reinforce the need for follow-up eye examinations through early grade school years in infants with high risk prethreshold ROP. PMID:21872933

Aggressive posterior retinopathy of prematurity in infants ≥ 1500 g birth weight.

PubMed

Sanghi, Gaurav; Dogra, Mangat R; Katoch, Deeksha; Gupta, Amod

2014-02-01

In this retrospective case series, we report the spectrum and outcomes of aggressive posterior retinopathy of prematurity (APROP) in infants ≥ 1500 g birth weight. Twenty-nine eyes of 15 infants are included. All infants were referred from level I or II nurseries, received supplemental unmonitored oxygen for prolonged duration (>1 week) and had multiple systemic co-morbidities. Of the 29 eyes, 10 (34.5%) had zone 1 and 19 (65.5%) had posterior zone 2 disease. Twenty-five (86.2%) eyes had flat neovascularization and 4 (13.8%) eyes had brush like proliferation. We noticed large vascular loops in 10 (34.5%) eyes. After confluent laser photocoagulation, 22 (75.9%) eyes had a favorable outcome. The study concludes that APROP in heavier (≥ 1500 g birth weight) premature infants occurs mostly in posterior zone 2 with flat neovascularization and atypical features like large vascular loops. Supplemental unmonitored oxygen for prolonged duration and multiple systemic co-morbidities could be a contributing factor.

Voluntary feed intake in rainbow trout is regulated by diet-induced differences in oxygen use.

PubMed

Saravanan, Subramanian; Geurden, Inge; Figueiredo-Silva, A Cláudia; Kaushik, Sadasivam; Verreth, Johan; Schrama, Johan W

2013-06-01

This study investigated the hypothesis that the voluntary feed intake in fish is regulated by diet-induced differences in oxygen use. Four diets were prepared with a similar digestible protein:digestible energy ratio (18 mg/kJ), but which differed in the composition of nonprotein energy source. This replacement of fat (F) by starch (S) was intended to create a diet-induced difference in oxygen use (per unit of feed): diets F30-S70, F50-S50, F65-S35, and F80-S20 with digestible fat providing 28, 49, 65, and 81% of the nonprotein digestible energy (NPDE), respectively. Each diet was fed to satiation to triplicate groups of 20 rainbow trout for 6 wk. As expected, diet-induced oxygen use decreased linearly (R(2) = 0.89; P < 0.001) with increasing NPDE as fat. The digestible and metabolizable energy intakes of trout slightly increased with increasing NPDE as fat (i.e., decreasing starch content) (R(2) = 0.30, P = 0.08; and R(2) = 0.34, P = 0.05, respectively). Oxygen consumption of trout fed to satiation declined with increasing dietary NPDE as fat (R(2) = 0.48; P = 0.01). The inverse relation between digestible energy intake of trout and the diet-induced oxygen use (R(2) = 0.33; P = 0.05) suggests a possible role of diet-induced oxygen use in feed intake regulation as shown by the replacement of dietary fat by starch.

Bcl-2 Family Members and Functional Electron Transport Chain Regulate Oxygen Deprivation-Induced Cell Death

PubMed Central

McClintock, David S.; Santore, Matthew T.; Lee, Vivian Y.; Brunelle, Joslyn; Budinger, G. R. Scott; Zong, Wei-Xing; Thompson, Craig B.; Hay, Nissim; Chandel, Navdeep S.

2002-01-01

The mechanisms underlying cell death during oxygen deprivation are unknown. We report here a model for oxygen deprivation-induced apoptosis. The death observed during oxygen deprivation involves a decrease in the mitochondrial membrane potential, followed by the release of cytochrome c and the activation of caspase-9. Bcl-XL prevented oxygen deprivation-induced cell death by inhibiting the release of cytochrome c and caspase-9 activation. The ability of Bcl-XL to prevent cell death was dependent on allowing the import of glycolytic ATP into the mitochondria to generate an inner mitochondrial membrane potential through the F1F0-ATP synthase. In contrast, although activated Akt has been shown to inhibit apoptosis induced by a variety of apoptotic stimuli, it did not prevent cell death during oxygen deprivation. In addition to Bcl-XL, cells devoid of mitochondrial DNA (ρ° cells) that lack a functional electron transport chain were resistant to oxygen deprivation. Further, murine embryonic fibroblasts from bax−/− bak−/− mice did not die in response to oxygen deprivation. These data suggest that when subjected to oxygen deprivation, cells die as a result of an inability to maintain a mitochondrial membrane potential through the import of glycolytic ATP. Proapoptotic Bcl-2 family members and a functional electron transport chain are required to initiate cell death in response to oxygen deprivation. PMID:11739725

Visible light optical coherence tomography measure retinal oxygen metabolic response to systemic oxygenation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

2016-03-01

The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. The rMRO2 was calculated by concurrent measurement of blood flow and blood oxygen saturation (sO2). Blood flow was calculated by the principle of Doppler optical coherence tomography, where the phase shift between two closely spaced A-lines measures the axial velocity. The distinct optical absorption spectra of oxy- and deoxy-hemoglobin provided the contrast for sO2 measurement, combined with the spectroscopic analysis of vis-OCT signal within the blood vessels. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28+/-0.08 μL/min (p<0.001), and 0.20+/-0.04 μL/min (p<0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation (CC).

Participation of reactive oxygen species in diabetes-induced endothelial dysfunction.

PubMed

Zúrová-Nedelcevová, Jana; Navarová, Jana; Drábiková, Katarína; Jancinová, Viera; Petríková, Margita; Bernátová, Iveta; Kristová, Viera; Snirc, Vladimír; Nosál'ová, Viera; Sotníková, Ruzena

2006-12-01

In the present study, the relationship between diabetes-induced hyperglycemia, reactive oxygen species production and endothelium-mediated arterial function was examined. The effect of antioxidant on the reactive oxygen species induced damage was tested. Diabetes was induced by streptozotocin (STZ), 3 x 30 mg/kg i.p., administered on three consecutive days. After 10 weeks of diabetes, the functional state of the endothelium of the aorta was tested, endothelemia evaluation was performed and systolic blood pressure was measured. Reactive oxygen species (ROS) formation in blood and the aorta was measured using luminol-enhanced chemiluminescence (CL). Levels of reduced glutathione (GSH) were determined in the aorta, kidney, and plasma. To study the involvement of hyperglycemia in functional impairment of the endothelium, aortal rings incubated in solution with high glucose concentration were tested in in vitro experiments. After 10 weeks of diabetes, endothelial injury was observed, exhibited by diminished endothelium-dependent relaxation of the aorta, increased endothelemia and by elevated systolic blood pressure. Using luminol-enhanced CL, a significant increase of ROS production was found in arterial tissue and blood. GSH levels were significantly increased in the kidney, while there were no GSH changes in plasma and the aorta. Incubation of aortic rings in solution with high glucose concentration led to impairment of endothelium-dependent relaxation. The synthetic antioxidant SMe1EC2 was able to restore reduced endothelium-mediated relaxation. Our results suggest an important role of hyperglycemia-induced ROS production in mediating endothelial dysfunction in experimental diabetes, confirmed by CL and the protective effect of the antioxidant SMe1EC2.

Diabetic retinopathy in patients with diabetic foot syndrome in South India

PubMed Central

Karam, Thoiba; Kamath, Yogish Subraya; Rao, Lavanya G; Rao, Krishna Addoor; Shenoy, Shailaja Bhat; Bhandary, Sulatha V

2018-01-01

Purpose: The purpose was to study the retinopathy status in diabetic patients with a risk of diabetic foot (DF) syndrome visiting a tertiary care hospital in South India. Methods: In this cross sectional study all patients with diabetes mellitus (DM) with a risk of DF syndrome, visiting a tertiary care hospital during the study period, underwent an ophthalmological evaluation for documentation of their retinopathy status. Results: One hundred and eighty-two patients diagnosed to have a risk profile for DF syndrome were included in the study. Their mean age was 59.28 years and 75.27% were males. The mean duration of Type 1 and Type 2 variants of DM was 14.9 years and 10.9 years, respectively. Of the 182 patients, 67.58% had retinopathy changes. Proliferative diabetic retinopathy (DR) constituted 17.88% of the total patients with retinopathy. An increased presence of retinopathy in patients with an increased risk grade of DF was found significant by the Chi-square test (P < 0.001). Conclusion: Our study found an increased presence of DR in a South Indian cohort with DF syndrome. The severity of retinopathy was greater in patients with higher grades of risk for DF. The establishment of an association between DR and DF syndrome will help in developing an integrated management strategy for these two debilitating consequences of diabetes. PMID:29582817