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Sample records for degeneration amd trial

  1. Subfoveal choroidal thickness predicts macular atrophy in age-related macular degeneration: results from the TREX-AMD trial.

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    Fan, Wenying; Abdelfattah, Nizar Saleh; Uji, Akihito; Lei, Jianqin; Ip, Michael; Sadda, SriniVas R; Wykoff, Charles C

    2018-03-01

    Our purpose was to evaluate the relationship between subfoveal choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with age-related macular degeneration (AMD). This was a prospective, multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial (NCT01648292) with treatment-naïve neovascular AMD (NVAMD) in at least one eye were included. SCT was measured by certified reading center graders at baseline using spectral domain optical coherence tomography (SDOCT). The baseline SCT was correlated with the presence of MA at baseline and development of incident MA by month 18. Generalized estimating equations were used to account for information from both eyes. Baseline SCT in eyes with MA was statistically significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04) and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and non-MA developers revealed a statistically significant difference (P = 0.03). Receiver operating characteristic curve (ROC) analysis showed the cut-off threshold of SCT for predicting the development of MA in cases without MA at baseline was 124 μm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among eyes without MA at baseline, those with baseline SCT ≤124 μm were 4.3 times more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P = 0.005) than those with baseline SCT >124 μm. Eyes with AMD and MA had less SCT than those without MA. Eyes with less baseline SCT also appear to be at higher risk to develop MA within 18 months.

  2. Transpalpebral electrotherapy for dry age-related macular degeneration (AMD): an exploratory trial.

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    Anastassiou, Gerasimos; Schneegans, Anna-Lena; Selbach, Michael; Kremmer, Stephan

    2013-01-01

    To evaluate the effect of transpalpebral electrotherapy on patients with dry age-related macular degeneration (AMD). 22 patients were randomized in two groups to either receive therapy (n = 12) or placebo (n = 10). There was no statistically significant difference for age and initial visual acuity (VA) between the two groups (p = 0.6; ANOVA). Treatment was performed on 5 consecutive days. On each day two sessions were applied. Every session included 8 spots (40 sec/spot) around the eye globe. The current applied (changing frequency 5-80 Hz) varied individually between 150 and 220 μA. Patients were examined before treatment, at the end of the 5-day treatment period, after 4 weeks and at 6 months. Examinations included a standardized VA testing, using ETDRS letters, contrast sensitivity, macular sensitivity and fixation stability using microperimetry and measurements with SD-OCT. At the end of week 1, mean VA improved markedly (p = 0.001; T test), with 7 out of 12 patients showing an improvement of more than 5 letters. After 4 weeks, there was an improvement of more than 10 letters in 3 patients (mean + 5.7 letters; p = 0.001; T test) whereas at 6 months a loss of 1.6 letters was observed. Only 4 (33%) of our patients did not show any improvement at all. Contrast sensitivity displayed a similar pattern. Within one week after treatment, there was a rapid improvement (+4.4 optotypes; p = 0.006; T test). After 6 months, contrast sensitivity declined again (+1.5 optotypes; p = 0.2; T test). Compared to the placebo group changes on VA failed statistical significance (p = 0.1 at 4 week; T test) whereas changes on contrast sensitivity were statistically significant (p = 0.01 at week 4; T test). No adverse events were seen or reported during the study period. To the best of our knowledge, this is the first report of a transpalpebral electrostimulation in patients with dry AMD that demonstrates a temporary increase in visual function in some of these patients; results that

  3. Age-related macular degeneration in a randomized controlled trial of low-dose aspirin: Rationale and study design of the ASPREE-AMD study

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    Liubov Robman

    2017-06-01

    Conclusion: The study findings will be of significant clinical and public interest due to a potential to identify a possible low cost therapy for preventing AMD worldwide and to determine risk/benefit balance of the aspirin usage by the AMD-affected elderly. The ASPREE-AMD study provides a unique opportunity to determine the effect of aspirin on AMD incidence and progression, by adding retinal imaging to an ongoing, large-scale primary prevention randomized clinical trial.

  4. Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.

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    Abdelfattah, Nizar S; Al-Sheikh, Mayss; Pitetta, Sean; Mousa, Ahmed; Sadda, SriniVas R; Wykoff, Charles C

    2017-02-01

    To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression. Eighteen-month, multicenter, randomized, controlled clinical trial. Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab. Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression. Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed. The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm 2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm 2 , respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 μm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 μm, P = 0.02) on MA. In

  5. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

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    Luis Fernando Hernández-Zimbrón

    2018-01-01

    Full Text Available Age-related macular degeneration (AMD is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the “dry” and the “wet” form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1 advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2 this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

  6. Harmonizing the classification of age-related macular degeneration in the three-continent AMD consortium

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    Klein, Ronald; Meuer, Stacy M; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Choudhury, Farzana; de Jong, Paulus T V M; McKean-Cowdin, Roberta; Iyengar, Sudha K; Gao, Xiaoyi; Lee, Kristine E; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Wang, Jie Jin; Klein, Barbara E K

    PURPOSE: To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), the Blue Mountains Eye Study (BMES), the Los Angeles Latino Eye Study (LALES), and the Rotterdam Study (RS).

  7. Low Nitric Oxide Synthases (NOS) in Eyes with Age-related Macular Degeneration (AMD)

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    Bhutto, Imran A.; Baba, Takayuki; Merges, Carol; McLeod, D. Scott; Lutty, Gerard A.

    2009-01-01

    Nitric oxide (NO) production by vascular endothelium is important in regulation of blood flow. Reduced production of NO can adversely affect blood flow and other vascular functions. We investigated the expression of three nitric oxide synthase (NOS) isoforms in retina and choroid of aged human eyes and eyes with AMD. Alkaline phosphatase immunohistochemistry was performed using antibodies against inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) NOSs on cryopreserved sections from aged control donor eyes (n= 13) and eyes with AMD (n= 22). CD34 antibody was used as an endothelial cell (EC) marker. Three independent masked observers scored the intensity of the immunohistochemical reaction product. Mean scores from the aged control and AMD eyes were statistically compared. In aged control retinas, nNOS was in ganglion cells (RGCs) and neurons of both nuclear layers. In choroid, perivascular nerve fibers and retinal pigment epithelial (RPE) cells were nNOS+. eNOS and iNOS were confined to the retinal and choroidal vascular ECs. Some cells presumably melanocytes or dendritic cells in choroid were also eNOS+. In AMD eyes, nNOS was significantly lower in RGCs, neurons, retinal vessels and RPE (p≤0.05) compared to the aged control eyes. iNOS and eNOS showed no significant differences between aged control and AMD eyes except that there was significantly less eNOS in choroidal arteries (p=0.006) and choroidal cells (p=0.03) of AMD eyes. Although NO was not measured directly, these findings suggest that there is less NO produced in AMD eyes. The decrease in retinal nNOS in AMD eyes is probably related to neuronal degeneration. The decrease in nNOS and eNOS in AMD choroid could be associated with vasoconstriction and hemodynamic changes. PMID:19836390

  8. Potential of Induced Pluripotent Stem Cells (iPSCs for Treating Age-Related Macular Degeneration (AMD

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    Mark Fields

    2016-12-01

    Full Text Available The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD, Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

  9. Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

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    Nashine, Sonali; Cohen, Pinchas; Chwa, Marilyn; Lu, Stephanie; Nesburn, Anthony B; Kuppermann, Baruch D; Kenney, M Cristina

    2017-07-20

    Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available

  10. Complement System in Pathogenesis of AMD: Dual Player in Degeneration and Protection of Retinal Tissue

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    Milosz P. Kawa

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness among the elderly, especially in Western countries. Although the prevalence, risk factors, and clinical course of the disease are well described, its pathogenesis is not entirely elucidated. AMD is associated with a variety of biochemical abnormalities, including complement components deposition in the retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex. Although the complement system (CS is increasingly recognized as mediating important roles in retinal biology, its particular role in AMD pathogenesis has not been precisely defined. Unrestricted activation of the CS following injury may directly damage retinal tissue and recruit immune cells to the vicinity of active complement cascades, therefore detrimentally causing bystander damage to surrounding cells and tissues. On the other hand, recent evidence supports the notion that an active complement pathway is a necessity for the normal maintenance of the neurosensory retina. In this scenario, complement activation appears to have beneficial effect as it promotes cell survival and tissue remodeling by facilitating the rapid removal of dying cells and resulting cellular debris, thus demonstrating anti-inflammatory and neuroprotective activities. In this review, we discuss both the beneficial and detrimental roles of CS in degenerative retina, focusing on the diverse aspects of CS functions that may promote or inhibit macular disease.

  11. Drugs in Phase II clinical trials for the treatment of age-related macular degeneration.

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    Tolentino, Michael John; Dennrick, Abrahan; John, Elizabeth; Tolentino, Michael Steven

    2015-02-01

    The clinical development of anti-VEGF therapies for the treatment of exudative age-related macular degeneration (wet AMD) has revolutionized ophthalmology. Indeed, it has provided clinicians and patients with treatments that lessen visual loss from in a disease that once was uniformly blinding. Although blindness is yet to be eradicated from AMD, repeated intraocular anti-VEGF injections are required to preserve a patient's vision. Therefore, further advances in this field are necessary. This review provides an overview of the agents that are in mid-stage phase trials for both exudative (wet AMD) and nonexudative macular degeneration (dry AMD). For wet AMD, new agents intend to enhance efficacy, develop alternative delivery such as eye drops, investigate alternate targets and construct sustained release strategies. For advanced dry AMD, the goal is to develop a strategy to slow or stop progressive loss of retinal tissue seen in geographic atrophy, the hallmark of advanced dry AMD. It is important to develop better more sensitive biomarkers, validating different approvable clinical trial endpoints and stratifying patients on their genetic polymorphisms. These developments should help to progress the already rapidly developing field of macular degeneration therapy.

  12. Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD).

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    Tokarz, Paulina; Kaarniranta, Kai; Blasiak, Janusz

    2013-10-01

    Cells in aerobic condition are constantly exposed to reactive oxygen species (ROS), which may induce damage to biomolecules, including proteins, nucleic acids and lipids. In normal circumstances, the amount of ROS is counterbalanced by cellular antioxidant defence, with its main components-antioxidant enzymes, DNA repair and small molecular weight antioxidants. An imbalance between the production and neutralization of ROS by antioxidant defence is associated with oxidative stress, which plays an important role in the pathogenesis of many age-related and degenerative diseases, including age-related macular degeneration (AMD), affecting the macula-the central part of the retina. The retina is especially prone to oxidative stress due to high oxygen pressure and exposure to UV and blue light promoting ROS generation. Because oxidative stress has an established role in AMD pathogenesis, proper functioning of antioxidant defence may be crucial for the occurrence and progression of this disease. Antioxidant enzymes play a major role in ROS scavenging and changes of their expression or/and activity are reported to be associated with AMD. Therefore, the enzymes in the retina along with their genes may constitute a perspective target in AMD prevention and therapy.

  13. Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

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    Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

    2018-01-01

    Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

  14. Five-year follow-up of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD)

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    Koev, K.; Avramov, L.; Borissova, E.

    2018-03-01

    The objective of this study was to examine long-term effects of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD). The research was implemented for a period of five years. For LLLT, a He-Ne Laser with continuous emission at 633 nm (0.1 mW/cm2) was used in patients with AMD of all stages (dry to wet exudative forms were included). In total, 33 patients (16 men and 17 women – 66 eyes) with AMD of various stages and a mean age of 68.7 ± 4.2 years were included in the study. Progressive, exudative AMD was diagnosed in 8 eyes. 58 eyes had drusen or were depigmented. Laser radiation was applied transpupillary to the macula for six times for three minutes once in two days; 22 patients with AMD (44 eyes) were randomly selected to receive mock treatment (control group 10 men and 12 women with a mean age of 69.3 ± 4.8 years). The visual acuity was followed for a five-year period. The perimetry and Amsler test were used to screen central scotomas. The fluorescein angiography of AMD and the control groups was examined. The visual acuity remained unchanged in all patients in the control group. There was a statistically significant increase in the visual acuity (pgroup was reduced. In conclusion, this study shows that LLLT may be a novel long-lasting therapeutic option for both forms of AMD. It is a highly-effective treatment that results in a long-term improvement of the visual acuity.

  15. C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration (AMD)

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    Bhutto, Imran A; Baba, Takayuki; Merges, Carol; Juriasinghani, Vikash; McLeod, D Scott; Lutty, Gerard A

    2016-01-01

    Background There is increasing evidence that inflammation and immune-mediated processes (complement activation) play an important role in age-related macular degeneration (AMD) pathogenesis. A genetic variation in the complement factor H (CFH) gene and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have been consistently shown to be associated with an increased risk for AMD. In the present study, we examined the immunolocalization of CRP and CFH in aged control human donor eyes (n=10; mean age 79 yrs) and eyes with AMD (n=18; mean age 83 yrs). Methods Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against CRP and CFH on cryopreserved tissue sections from disc/macular blocks. Three independent masked observers scored the reaction product (0-8). Results In aged control eyes, the retinal pigment epithelium/Bruch’s membrane/choriocapillaris (RPE/BrM/CC) complex including intercapillary septa (ICS) had the most prominent immunostaining for CRP and CFH. CRP was significantly higher than controls in BrM/CC/ICS and choroidal stroma in early and wet AMD eyes (p<0.05). In contrast, CFH was significantly lower in BrM/CC/ICS complex of AMD choroids than in controls (p<0.05). Interestingly, CRP and CFH were significantly reduced in BrM/CC/ICS complex in atrophic area of macula in geographic atrophy (GA)(p<0.05). Drusen and basal laminar deposits were intensely positive for CRP and CFH. Conclusion These immunohistochemical findings show that changes in distribution and relative levels of CRP and CFH were evident in early and late AMD eyes. This suggests that high levels of CRP and insufficient CFH at the retina/choroid interface may lead to uncontrolled complement activation with associated cell and tissue damage. This study supports the hypothesis that inflammation and immune-mediated mechanisms are involved in the pathogenesis of AMD. PMID:21633121

  16. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

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    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Regression of Some High-risk Features of Age-related Macular Degeneration (AMD in Patients Receiving Intensive Statin Treatment

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    Demetrios G. Vavvas

    2016-03-01

    Conclusions: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

  18. Association between Antiplatelet or Anticoagulant Drugs and Retinal/subretinal Hemorrhage in the Comparison of AMD Treatments Trials (CATT)

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    Ying, Gui-shuang; Maguire, Maureen G.; Daniel, Ebenezer; Grunwald, Juan E; Ahmed, Osama; Martin, Daniel F.

    2015-01-01

    Objective To evaluate the association between use of antiplatelet (AP) or anticoagulant (AC) drugs and retinal/subretinal hemorrhage in participants with neovascular age-related macular degeneration (AMD) in the Comparison of AMD Treatments Trials (CATT). Design Cohort study within CATT. Methods 1185 CATT participants with untreated active neovascular AMD were interviewed for use of AP/AC drugs. Trained readers evaluated photographs for the presence and size of retinal/subretinal hemorrhage associated with the neovascular lesion at baseline and years 1 and 2. Associations between use of AP/AC drugs and hemorrhage were evaluated among all participants and by baseline hypertension status using Fisher exact test and multivariate logistic regression models. Main Outcome Measures Odds ratio for association with AP/AC use. Results Among 1165 participants with gradable photographs, 724 (62.1%) had retinal/subretinal hemorrhage at baseline, 84.4% of hemorrhages were ≤ 1 DA, 8.1% were 1 to 2 DA, and 7.5% were >2 DA. 608 (52.2%) participants used AP/AC drugs at baseline, including 514 (44.1%) AP only, 77 (6.6%) AC only, and 17 (1.5%) both AP and AC. Participants with retinal/subretinal hemorrhage at baseline were comparable to those without retinal/subretinal hemorrhage except that they were older (80 vs. 78 years, phemorrhage was present in 64.5% of AP/AC users and in 59.6% of non-users (p=0.09), the adjusted odds ratio (OR) was 1.18 (95% CI: 0.91–1.51, p=0.21). Neither presence nor size of baseline retinal/subretinal hemorrhage was associated with the type, dose or duration of AP/AC use. Forty-four (4.08%) of 1078 participants had retinal/subretinal hemorrhage detected on 1-year or 2-year photographs; these hemorrhages were not associated with AP/AC use at baseline (p=0.28) or during follow-up (p=0.64). Among participants with hypertension (N=807), AP/AC use was associated with higher rate of retinal/subretinal hemorrhage at baseline (66.8% vs. 56.4%, adjusted OR=1

  19. Complement pathway biomarkers and age-related macular degeneration

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    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  20. The emotional and physical impact of wet age-related macular degeneration: findings from the wAMD Patient and Caregiver Survey

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    Varano M

    2016-02-01

    Full Text Available Monica Varano,1 Nicole Eter,2 Steve Winyard,3 Kim U Wittrup-Jensen,4 Rafael Navarro,5 Julie Heraghty6 On behalf of the wAMD Patient and Caregiver Survey Committee members 1Department of Ophthalmology, Fondazione GB Bietti-IRCCS, Rome, Italy; 2Department of Ophthalmology, University of Münster, Münster, Germany; 3Department of Policy and Campaigns, Royal National Institute of Blind People, London, UK; 4Bayer Pharma AG, Berlin, Germany; 5Instituto de Microcirugia Ocular, Barcelona, Spain; 6Macular Disease Foundation Australia, Sydney, NSW, Australia Objectives: This was a cross-sectional survey to evaluate the physical and emotional impact of wet age-related macular degeneration (wAMD on a global cohort of patients who were receiving (or had previously received antivascular endothelial growth factor injections, and caregivers (paid and unpaid.Methods: The survey was performed in nine countries using an ophthalmologist-devised questionnaire.Results: A total of 910 patients and 890 caregivers completed the questionnaire. Most patients had been diagnosed and receiving antivascular endothelial growth factor injections for more than 1 year (74.7% and 63.8%, respectively, and many patients (82.1% received support from a caregiver (usually a child/grandchild [47.3%] or partner [23.3%]. wAMD had a negative impact on most patients (71.6%; many rated fear (44.9%, sadness (39.9%, frustration (37.3%, and depression (34.0% as common. It was linked to physical consequences, such as difficulty in reading (61.1%. Many effects were significantly greater in patients with a longer duration of disease or with wAMD in both eyes. Some caregivers (unpaid also reported that caregiving had a negative impact on them (31.1%; many reported emotions such as sadness (34.9% and depression (24.4%, but many also felt useful (48.4%. Overall, 27.2% of caregivers (unpaid rated caregiving as inconvenient; this was linked to days of employment/personal obligations missed

  1. Update on Clinical Trials in Dry Age-related Macular Degeneration

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    Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  2. Low vision depression prevention trial in age-related macular degeneration: a randomized clinical trial.

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    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Ho, Allen C; Tasman, William S

    2014-11-01

    To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry

  3. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial

    OpenAIRE

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-01

    Objective An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. Methods In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor’s instr...

  4. TU-F-CAMPUS-T-02: Monte Carlo Evaluation of Kilovoltage Radiosurgery with AuNPs for Age Related Macular Degeneration (AMD)

    International Nuclear Information System (INIS)

    Brivio, D; Zygmanski, P; Sajo, E; Makrigiorgos, G; Ngwa, W

    2015-01-01

    Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery of Age related Macular Degeneration (AMD) using Monte Carlo (MC) simulation. AMD disease causes vision loss due to a leaky vasculature of the endothelial cells. Radiosurgical therapy aims to destroy this vasculature while minimizing the delivered dose to healthy tissues of the eye. AuNP known to enhance local dose have been targeted to the macular choroidal endothelial cells to increase the therapeutic efficacy. Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a thin layer of AuNP has been calculated by a MC radiation transport simulation. AuNP layer (10–100nm) has been placed on the bottom of the macula at 2.4cm depth in a water parallelepiped 3×3×6cm3. This layer has been modeled considering various concentrations of AuNP ranging from 5.5–200mg per gram of endothelial cell (volume 10×10×2um3). The x-ray source is 100kVp 4mm diameter beam tilted 0°-30° with respect to the lens. Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown experimentally feasible) and 10–100nm sizes is about 1.8. Tilting 4mm-beam does not reduce the enhancement but allows to avoid the surrounding tissues. Dose distribution in the AuNP vicinity has a significant increase within 30um, peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field are the same while the actual delivered dose is more than one order of magnitude lower outside the field. Compared to 100kVp, usage of filtered spectra with enhanced flux in the region 20keV-40keV shows further increase of DER by about 20%. Dose to the neighboring organs such as retina/optic nerve are reduced accordingly. Conclusion: The results of this MC simulation provide further confirmation of the potential to enhance DER with AuNP from previous analytical calculations. This study provides impetus to improve treatment effectiveness of AMD disease with radiotherapy

  5. TU-F-CAMPUS-T-02: Monte Carlo Evaluation of Kilovoltage Radiosurgery with AuNPs for Age Related Macular Degeneration (AMD)

    Energy Technology Data Exchange (ETDEWEB)

    Brivio, D; Zygmanski, P [Brigham & Women’s Hospital, Boston, MA (United States); Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Makrigiorgos, G [Dana Farber Cancer Institute, Boston, MA (United States); Ngwa, W [Harvard Medical School, Boston, MA (United States)

    2015-06-15

    Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery of Age related Macular Degeneration (AMD) using Monte Carlo (MC) simulation. AMD disease causes vision loss due to a leaky vasculature of the endothelial cells. Radiosurgical therapy aims to destroy this vasculature while minimizing the delivered dose to healthy tissues of the eye. AuNP known to enhance local dose have been targeted to the macular choroidal endothelial cells to increase the therapeutic efficacy. Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a thin layer of AuNP has been calculated by a MC radiation transport simulation. AuNP layer (10–100nm) has been placed on the bottom of the macula at 2.4cm depth in a water parallelepiped 3×3×6cm3. This layer has been modeled considering various concentrations of AuNP ranging from 5.5–200mg per gram of endothelial cell (volume 10×10×2um3). The x-ray source is 100kVp 4mm diameter beam tilted 0°-30° with respect to the lens. Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown experimentally feasible) and 10–100nm sizes is about 1.8. Tilting 4mm-beam does not reduce the enhancement but allows to avoid the surrounding tissues. Dose distribution in the AuNP vicinity has a significant increase within 30um, peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field are the same while the actual delivered dose is more than one order of magnitude lower outside the field. Compared to 100kVp, usage of filtered spectra with enhanced flux in the region 20keV-40keV shows further increase of DER by about 20%. Dose to the neighboring organs such as retina/optic nerve are reduced accordingly. Conclusion: The results of this MC simulation provide further confirmation of the potential to enhance DER with AuNP from previous analytical calculations. This study provides impetus to improve treatment effectiveness of AMD disease with radiotherapy.

  6. The macular degeneration and aging study: Design and research protocol of a randomized trial for a psychosocial intervention with macular degeneration patients.

    Science.gov (United States)

    Sörensen, Silvia; White, Katherine; Mak, Wingyun; Zanibbi, Katherine; Tang, Wan; O'Hearn, Amanda; Hegel, Mark T

    2015-05-01

    Age-related Macular Degeneration (AMD) is the leading cause of irreversible and predictable blindness among older adults with serious physical and mental health consequences. Visual impairment is associated with negative future outlook and depression and has serious consequences for older adults' quality of life and, by way of depression, on long-term survival. Psychosocial interventions have the potential to alleviate and prevent depression symptoms among older AMD patients. We describe the protocol of the Macular Degeneration and Aging Study, a randomized clinical trial of a psychosocial Preventive Problem-Solving Intervention. The intervention is aimed at enhancing well-being and future planning among older adults with macular degeneration by increasing preparation for future care. Adequate randomization and therapeutic fidelity were achieved. Current retention rates were acceptable, given the vulnerability of the population. Acceptability (adherence and satisfaction) was high. Given the high public health significance and impact on quality of life among older adults with vision loss, this protocol contributes a valid test of a promising intervention for maintaining mental and physical health in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

    International Nuclear Information System (INIS)

    Brivio, D; Zygmanski, P; Makrigiorgos, G M; Ngwa, W; Arnoldussen, M; Hanlon, J; Chell, E; Sajo, E

    2015-01-01

    This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g −1 , which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP. (paper)

  8. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

    Science.gov (United States)

    Brivio, D.; Zygmanski, P.; Arnoldussen, M.; Hanlon, J.; Chell, E.; Sajo, E.; Makrigiorgos, G. M.; Ngwa, W.

    2015-12-01

    This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g-1, which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

  9. on visual acuity in age related macular degeneration

    African Journals Online (AJOL)

    marine origin) in the treatment of age related macular degeneration (AMD). In a randomized double blind clinical trial 280 eyes of 280 (157 F, 123 M) patients with wet and dry AMD were randomly assigned in treatment or placebo groups. Patients in ...

  10. Improving function in age-related macular degeneration: a randomized clinical trial.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Ho, Allen C; Tasman, William S

    2013-08-01

    To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD). Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Patients with AMD (n = 241) attending retina practices. Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment. We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life (QoL). There were no between-group differences in TVF scores at 3 (P = 0.47) or 6 (P = 0.62) months. For PST subjects, mean ± standard deviation TVF scores improved from 2.71±0.52 at baseline to 2.18±0.88 at 3 months (P = 0.001) and were 2.18±0.95 at 6 months (change from 3 to 6 months, P = 0.74). For ST subjects, TVF scores improved from 2.73±0.52 at baseline to 2.14±0.96 at 3 months (P = 0.001) and were 2.15±0.96 at 6 months (change from 3 to 6 months, P = 0.85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs 78.6%, respectively; P = 0.83) and 6 months (76.2% vs 79.1%, respectively; P = 0.61). There were no changes in the NEI VFQ or AI. Vision-related QoL improved for PST relative to ST subjects at 3 months (F(4, 192) = 2.46; P = 0.05) and at 6 months (F(4, 178) = 2.55; P = 0.05). The PST subjects also developed more adaptive coping strategies than ST subjects. We found that PST was not superior to ST at improving vision function in patients with AMD, but that PST improved their vision-related QoL. Despite the benefits of anti-vascular endothelial growth factor treatments, AMD remains associated with disability, depression, and diminished QoL. This clinical reality necessitates new rehabilitative

  11. Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD

    Directory of Open Access Journals (Sweden)

    Nur Afiqah Mohamad

    2018-03-01

    Full Text Available Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF therapy in patients with neovascular form of AMD (nAMD may be due to polymorphisms in the complement factor H gene (CFH. This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE regimen. Best-corrected visual acuity (BCVA and central retinal thickness (CRT were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170 polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49 and non-responder (n = 84 group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018. Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05. Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.

  12. Low Vision Depression Prevention Trial in Age-Related Macular Degeneration

    Science.gov (United States)

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2014-01-01

    Purpose To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Design Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Participants Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Interventions Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Main Outcome Measures The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire–25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). Results At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27–1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27–0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. Conclusions An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid

  13. Outer retinal tubulation in the comparison of age-related macular degeneration treatments trials (CATT).

    Science.gov (United States)

    Lee, Joo Yong; Folgar, Francisco A; Maguire, Maureen G; Ying, Gui-shuang; Toth, Cynthia A; Martin, Daniel F; Jaffe, Glenn J

    2014-12-01

    To determine the prevalence of, risk factors for, and visual acuity (VA) correlations with outer retinal tubulation (ORT) seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) after anti-vascular endothelial growth factor (VEGF) therapy. Prospective cohort study within a randomized clinical trial. Patients with SD OCT images at weeks 56 and 104 in the Comparison of AMD Treatments Trials (CATT). Participants in the CATT were assigned randomly to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a monthly or pro re nata (PRN) injection-dosing regimen. A subset of eyes was imaged with SD OCT beginning at week 56. Cirrus 512×128 or Spectralis 20°×20° volume cube scan protocols were used to acquire SD OCT images. Two independent readers at the CATT OCT reading center graded scans, and a senior reader arbitrated discrepant grades. The prevalence of ORT, identified as tubular structures seen on at least 3 consecutive Cirrus B scans or 2 consecutive Spectralis B scans, was determined. The associations of patient-specific and ocular features at baseline and follow-up with ORT were evaluated by univariate and multivariate analyses. Outer retinal tubulations. Seven of 69 eyes (10.1%) at 56 weeks and 64 of 368 eyes (17.4%) at week 104 had ORTs. Absence of diabetes, poor VA, blocked fluorescence, geographic atrophy, greater lesion size, and presence of subretinal hyperreflective material at baseline were associated independently with greater risk of ORT at 104 weeks (P Diabetic Retinopathy Study letters) was worse than the mean VA of eyes without ORT (68.8 letters; P predict ORTs. It is important to identify ORTs because eyes with ORTs have worse VA outcomes than those without this finding. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  14. Radiotherapy of macular lesions in age-related macular degeneration (A.M.D.): preliminary results of a clinical study conducted in Lyon, France; Radiotherapie des degenerescences maculaires liees a l`age (DMLA): resultats preliminaires d`une etude lyonnaise

    Energy Technology Data Exchange (ETDEWEB)

    Martin, P. [Centre oncologie radiotherapie Saint-Jean, 69 - Lyon (France); Mauget, M. [Centre ophtalmologique d`imagerie, laser, 69 - Lyon (France); Gerard, J.P. [Service de radiotherapie-oncologie, CHU Lyon Sud, 69 - Pierre-Benite (France) (and others)

    1997-06-01

    To evaluate irradiation effects on functional signs and choroidal neo-vascular lesions in age-related macular degeneration (AMD) that does not respond to laser therapy. Since 1994, 250 consecutive AMD patients were treated by two radiotherapy teams for sub-foveal neo-vascular lesions. At the end of september 1996, 52 patients were evaluable with a 1-year follow-up. Group 1 (Department de Radiotherapie Oncologie, Centre Hospitalo-Universitaire Lyon Sud) included 26 patients who were treated with a lateral beam of 6 MV photons. The irradiation dose were 20 Gy in five fractions for small lesions and 28.8 Gy in eight fractions for larger lesions. Group 2 (Centre Oncologie Radiotherapie Saint-Jean) was composed of 26 patients treated with a mini-beam of 25 MV photons via lateral arc-therapy. Beam diameters (14 and 18 mm) were adapted to the lesion size. The total dose was 16 Gy in four fractions or 20 Gy in five fractions. Functional and anatomical results were assessed at 3, 6, 9 months and 1 year after radiation therapy. Stable visual acuity was observed in 44 % (23/52) of the patients and visual acuity was improved in 35 % (18/52) of the patients at 6 months. Good functional results reached 79 % (41/52) at 6 months and 74 % (17/23) at 12 months. There was no statistical difference between the two groups and dose levels. All severe complications (1 cataract, 3 dilated choroidal vessels, and 2 papillitis) occurred in group 1. Though it is too early to conclude on the best dose level, radiotherapy of sub-foveal neo-vascular lesions of AMD that cannot be treated via laser therapy provides encouraging results. The technique used must be very precise to adequately irradiate the fovea and spare surrounding sensitive areas. Further studies and trials involving patients` randomization are necessary to confirm these preliminary results. (author) 13 refs.

  15. The role of free-radical processes in the pathogenesis of age-related macular degeneration. Review

    Directory of Open Access Journals (Sweden)

    A. V. Kolesnikov

    2012-01-01

    Full Text Available the modern ideas of the role of free radical processes in the pathogenesis of age-related macular degeneration (AMD are consid- ered. Data of large randomized clinical trials on application of antioxidants for prevention and therapy AMD are provided. Possibility of the differential application of antioxidants depending on the genetic status of patients is discussed.

  16. Overview of clinical trials for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Cheng

    2017-01-01

    Full Text Available The overall goal of treating age-related macular degeneration (AMD is to target the underlying cause of the disease and prevent, or at least slow down, the loss of vision, which requires the preservation of the choroid, retinal pigment epithelium (RPE, and photoreceptors. At present, there is no proven drug treatment for dry AMD; however, the cessation of smoking and treatments based on the age-related eye diseases study vitamin formula combined with a healthy diet are considered the only options for slowing disease progression. A number of pharmaceutical agents are currently under evaluation for the treatment of dry AMD using strategies such as reduction RPE and photoreceptor loss, neuroprotection, visual cycle modulators, suppression of inflammation, prevention of oxidative damage, and choroidal perfusion enhancers. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.

  17. Stem cells in clinical trials for treatment of retinal degeneration.

    Science.gov (United States)

    Klassen, Henry

    2016-01-01

    After decades of basic science research involving the testing of regenerative strategies in animal models of retinal degenerative diseases, a number of clinical trials are now underway, with additional trials set to begin shortly. These efforts will evaluate the safety and preliminary efficacy of cell-based products in the eyes of patients with a number of retinal conditions, notably including age-related macular degeneration, retinitis pigmentosa and Stargardt's disease. This review considers the scientific work and early trials with fetal cells and tissues that set the stage for the current clinical investigatory work, as well the trials themselves, specifically those either now completed, underway or close to initiation. The cells of interest include retinal pigment epithelial cells derived from embryonic stem or induced pluripotent stem cells, undifferentiated neural or retinal progenitors or cells from the vascular/bone marrow compartment or umbilical cord tissue. Degenerative diseases of the retina represent a popular target for emerging cell-based therapeutics and initial data from early stage clinical trials suggest that short-term safety objectives can be met in at least some cases. The question of efficacy will require additional time and testing to be adequately resolved.

  18. Tapping Stem Cells to Target AMD: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Caroline Brandl

    2015-01-01

    Full Text Available Human pluripotent stem cells (hPSCs are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD, the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs, in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.

  19. Prevention and treatment of age-related macular degeneration: an update for pharmacists.

    Science.gov (United States)

    Marshall, Leisa L; Roach, J Michael

    2013-11-01

    Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

  20. Cellular models and therapies for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

    Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

  1. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

    Directory of Open Access Journals (Sweden)

    Bunce Catey

    2008-10-01

    Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

  2. Potential of epigenetic mechanisms in AMD pathology.

    Science.gov (United States)

    Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2013-01-01

    Age-related macular degeneration (AMD) is an ocular disease and the main reason for sight loss in the elderly in the developed countries. The pathogenesis of the disease is complex and not fully understood, but involves several environmental and genetic risk factors. However, little is known about the role of epigenetics in this disease although it is recognized that epigenetic alterations often precede genetic changes in many pathological conditions and regulate aging and the developmental processes. There is experimental evidence for the involvement of DNA methylation and histone modifications in the pathogenesis of drusen formation, a central hallmark of AMD. However, the main impact of epigenetic modifications, including persistent lysine methylation of the H3 histone, is exerted during retinal embryonic development. This interplay opens an exciting possibility to manipulate the epigenetic pattern and to develop novel AMD therapies by physical, pharmacological or genetic interventions. One of the most intriguing questions is why different individuals develop different AMD phenotypes. Epigenetic regulation might open new perspectives into these changes in AMD pathology.

  3. CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.

    Directory of Open Access Journals (Sweden)

    Kristinn P Magnusson

    2006-01-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in the Complement Factor H (CFH gene increases the risk for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD--or the relationship between them--is unclear.We genotyped 581 Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with mixed neovascular AMD/GA, and 435 with early AMD (of whom 220 had soft drusen. A second cohort of 431 US patients from Utah, 322 with advanced AMD (244 neovascular AMD and 78 GA and 109 early-AMD cases with soft drusen, were analyzed. We confirmed that the CFH Y402H variant shows significant association to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 x 10(-12 and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 10(-9 with advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of soft drusen and both forms of advanced AMD (GA or neovascular AMD.Soft drusen occur prior to progression to advanced AMD and represent a histological feature shared by neovascular AMD and GA. Our results suggest that CFH is a major risk factor of soft drusen, and additional genetic factors and/or environmental factors may be required for progression to advanced AMD.

  4. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    Science.gov (United States)

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.

  5. Outcomes of eyes with lesions composed of >50% blood in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

    Science.gov (United States)

    Altaweel, Michael M; Daniel, Ebenezer; Martin, Daniel F; Mittra, Robert A; Grunwald, Juan E; Lai, Michael M; Melamud, Alexander; Morse, Lawrence S; Huang, Jiayan; Ferris, Frederick L; Fine, Stuart L; Maguire, Maureen G

    2015-02-01

    To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with >50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a multicenter randomized clinical trial. CATT patients with neovascular age-related macular degeneration (AMD). Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA. Morphologic features and VA at 1 and 2 years. The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P 50% blood can be managed similarly to those with less or no blood. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  6. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV......Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...... individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single...

  7. Age-Related Macular Degeneration.

    Science.gov (United States)

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study

    NARCIS (Netherlands)

    Schauwvlieghe, A. M. E.; Dijkman, G.; Hooymans, J. M.; Verbraak, F. D.; Hoyng, C. B.; Dijkgraaf, M. G. W.; Peto, T.; Vingerling, J. R.; Schlingemann, R. O.

    2016-01-01

    To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD). Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters. Patients ≥ 60 years of age with primary or

  9. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Directory of Open Access Journals (Sweden)

    Allen Taylor

    2013-07-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS II intervention trial should be particularly informative.

  10. The results of randomized controlled trial of low-dose radiation for wet-type age-related macular degeneration on a 1 year term basis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-06-01

    Evaluation of low dose radiation therapy to the wet-type age-related macular degeneration (AMD) located at the fovea centralis. Patients were irradiated with 10 fractions of 2 Gy external beam or just observed. Between the treated (39) and untreated (31) cases, there was no significant difference in gender, age, initial visual acuity, or size of the neovascular membrane. With the follow-up of 12 months, the visual acuity was significantly well preserved and the size of the neovascular membrane was decreased. These results indicate that low dose irradiation is effective for the wet-type AMD of the stage we treated in the present study. (author)

  11. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

    Directory of Open Access Journals (Sweden)

    Miltiadis K. Tsilimbaris

    2016-01-01

    Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

  12. Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images.

    Science.gov (United States)

    Chiu, Stephanie J; Izatt, Joseph A; O'Connell, Rachelle V; Winter, Katrina P; Toth, Cynthia A; Farsiu, Sina

    2012-01-05

    To automatically segment retinal spectral domain optical coherence tomography (SD-OCT) images of eyes with age-related macular degeneration (AMD) and various levels of image quality to advance the study of retinal pigment epithelium (RPE)+drusen complex (RPEDC) volume changes indicative of AMD progression. A general segmentation framework based on graph theory and dynamic programming was used to segment three retinal boundaries in SD-OCT images of eyes with drusen and geographic atrophy (GA). A validation study for eyes with nonneovascular AMD was conducted, forming subgroups based on scan quality and presence of GA. To test for accuracy, the layer thickness results from two certified graders were compared against automatic segmentation results for 220 B-scans across 20 patients. For reproducibility, automatic layer volumes were compared that were generated from 0° versus 90° scans in five volumes with drusen. The mean differences in the measured thicknesses of the total retina and RPEDC layers were 4.2 ± 2.8 and 3.2 ± 2.6 μm for automatic versus manual segmentation. When the 0° and 90° datasets were compared, the mean differences in the calculated total retina and RPEDC volumes were 0.28% ± 0.28% and 1.60% ± 1.57%, respectively. The average segmentation time per image was 1.7 seconds automatically versus 3.5 minutes manually. The automatic algorithm accurately and reproducibly segmented three retinal boundaries in images containing drusen and GA. This automatic approach can reduce time and labor costs and yield objective measurements that potentially reveal quantitative RPE changes in longitudinal clinical AMD studies. (ClinicalTrials.gov number, NCT00734487.).

  13. The molecular genetic basis of age-related macular degeneration ...

    Indian Academy of Sciences (India)

    Keywords. AMD; epidemiology; genes; polymorphism; risk. Abstract. Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly.

  14. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  15. Current drug and molecular therapies for the treatment of atrophic age-related macular degeneration: phase I to phase III clinical development.

    Science.gov (United States)

    Li, Huiling; Chintalapudi, Sumana R; Jablonski, Monica M

    2017-10-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. Atrophic AMD, including early, intermediate and geographic atrophy (GA), accounts for ~90% of all cases. It is a multifactorial degeneration characterized by chronic inflammation, oxidative stress and aging components. Although no FDA-approved treatment yet exists for the late stage of atrophic AMD, multiple pathological mechanisms are partially known and several promising therapies are in various stages of development. Areas covered: Underlying mechanisms that define atrophic AMD will help provide novel therapeutic targets that will address this largely unmet clinical need. The purpose of this paper is to review current promising drugs that are being evaluated in clinical trials. Because no pharmacological treatments are currently available for late stage of atrophic AMD, any new therapy would have extensive market potential. Expert opinion: The number of AMD patients is predicted to increase to ~30 million worldwide by 2020. In response to this enormous unmet clinical need, new promising therapies are being developed and evaluated in clinical trials. We propose that the assessment of novel interventions will also need to consider the genotypes of participants, as the benefit may be determined by polymorphisms in an individual's genetic background.

  16. How does age-related macular degeneration affect real-world visual ability and quality of life? A systematic review

    Science.gov (United States)

    Taylor, Deanna J; Hobby, Angharad E; Binns, Alison M; Crabb, David P

    2016-01-01

    Objectives To review systematically the evidence of age-related macular degeneration (AMD) affecting real-world visual ability and quality of life (QoL). To explore trends in specific topics within this body of the literature. Design Systematic review. Methods A systematic literature search was carried out using MEDLINE, EMBASE, CINAHL, PsycINFO, PsychARTICLES and Health and Psychosocial Instruments for articles published up to January 2015 for studies including people diagnosed with AMD, assessing real-world visual ability or QoL as an outcome. Two researchers screened studies for eligibility. Details of eligible studies including study design, characteristics of study population and outcomes measured were recorded in a data extraction table. All included studies underwent quality appraisal using the Mixed Methods Appraisal Tool 2011 Version (MMAT). Results From 5284 studies, 123 were eligible for inclusion. A range of approaches were identified, including performance-based methods, quantitative and qualitative patient-reported outcome measures (PROMs). AMD negatively affects tasks including mobility, face recognition, perception of scenes, computer use, meal preparation, shopping, cleaning, watching TV, reading, driving and, in some cases, self-care. There is evidence for higher rates of depression among people with AMD than among community dwelling elderly. A number of adaptation strategies have been associated with AMD of varying duration. Much of the research fails to report the type of AMD studied (59% of included studies) or the duration of disease in participants (74%). Of those that do report type studied, the breakdown is as follows: wet AMD 20%, dry AMD 4% and both types 17%. Conclusions There are many publications highlighting the negative effects of AMD in various domains of life. Future research should focus on delivering some of this research knowledge into patient management and clinical trials and differentiating between the types of AMD. PMID

  17. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial.

    Science.gov (United States)

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-22

    An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor's instructions for vision monitoring; Amsler grid). At 6 and/or 12 months post-enrollment, 157 subjects completed a questionnaire on vision self-monitoring. At 6 and 12 months, respectively, 85% and 80% of the VMS journal subjects reported vision monitoring at least weekly, which represent statistically significant 7.1 and 4.2 times greater odds than the 50% of controls who monitored weekly at both follow-up times (pself-monitoring. At 6 and 12 months, respectively, only 15% and 13% of the VMS journal subjects vs. 53% and 44% of the controls reported that they did not feel confident that they were taking care of their sight by self-monitoring (pself-monitoring between the groups (p=0.68), with 81% of all subjects reporting no change in frequency between 6 and 12 months. These findings support the efficacy of the VMS journal for increasing vision self-monitoring adherence and confidence, in addition to promoting persistence in weekly monitoring over the course of a year in AMD subjects at risk for exudative retinal changes.

  18. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial

    Science.gov (United States)

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-01

    Objective An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. Methods In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor’s instructions for vision monitoring; Amsler grid). At 6 and/or 12 months post-enrollment, 157 subjects completed a questionnaire on vision self-monitoring. Results At 6 and 12 months, respectively, 85% and 80% of the VMS journal subjects reported vision monitoring at least weekly, which represent statistically significant 7.1 and 4.2 times greater odds than the 50% of controls who monitored weekly at both follow-up times (psight by self-monitoring (p<0.001). Usual care controls had statistically significant 6.7 and 5.0 times greater odds of reporting non-confidence at 6 and 12 months, respectively. There was no statistically significant change in weekly vs. less frequent self-monitoring between the groups (p=0.68), with 81% of all subjects reporting no change in frequency between 6 and 12 months. Conclusions These findings support the efficacy of the VMS journal for increasing vision self-monitoring adherence and confidence, in addition to promoting persistence in weekly monitoring over the course of a year in AMD subjects at risk for exudative retinal changes. PMID:24791222

  19. The arm motion detection (AMD) test.

    Science.gov (United States)

    Bengtson, Maria C; Mrotek, Leigh A; Stoeckmann, Tina; Ghez, Claude; Scheidt, Robert A

    2014-01-01

    Stroke can lead to sensory deficits that impair functional control of arm movements. Here we describe a simple test of arm motion detection (AMD) that provides an objective, quantitative measure of movement perception related proprioceptive capabilities in the arm. Seven stroke survivors and thirteen neurologically intact control subjects performed the AMD test. In a series of ten trials that took less than 15 minutes to complete, participants used a two-button user interface to adjust the magnitude of hand displacements produced by a horizontal planar robot until the motions were just perceptible (i.e. on the threshold of detection). The standard deviation of movement detection threshold was plotted against the mean and a normative range was determined from the data collected with control subjects. Within this normative space, subjects with and without intact proprioception could be discriminated on a ratio scale that is meaningful for ongoing studies of degraded motor function. Thus, the AMD test provides a relatively fast, objective and quantitative measure of upper extremity proprioception of limb movement (i.e. kinesthesia).

  20. Age-related macular degeneration and quality of life: how to interpret a research paper in health-related quality of life.

    Science.gov (United States)

    Sharma, Sanjay; Oliver-Fernandez, Alejandro

    2004-06-01

    To review how to critically appraise a research article pertaining to changes in health-related quality of life (HRQoL) related to interventions for age-related macular degeneration (AMD). We searched PubMed using a strategy that combined the text-words, "macular degeneration" and "quality of life" (n = 73; January 17, 2004), while limiting the search to "clinical trials" (n = 6; of which 3 were published within the past year). A randomized clinical trial evaluating the efficacy of self-management as an intervention for AMD has been selected to introduce the reader to the concept of how to critically review a research paper pertaining to HRQoL in AMD. Other pertinent articles used in this review include recent results published from the Age-Related Eye Disease Study and the Submacular Surgery Trial. The NEI-VFQ is a reliable, valid, and responsive tool when applied to patients with AMD. Self-management of patients with AMD has been demonstrated to improve their HRQoL by way of an internally valid randomized clinical trial. In this issue of Current Opinion in Ophthalmology, we confront the issue of how to assess the validity and importance of a research paper pertaining to the issue of quality of life. To introduce this topic, we will present a real world clinical example to better understand how quality of life may aid in medical decision making.

  1. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  2. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Larsen, Michael; Munch, Inger Christine

    2012-01-01

    To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older.......To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older....

  3. Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration.

    Science.gov (United States)

    Guymer, Robyn H; Baird, Paul N; Varsamidis, Mary; Busija, Lucy; Dimitrov, Peter N; Aung, Khin Zaw; Makeyeva, Galina A; Richardson, Andrea J; Lim, Lyndell; Robman, Liubov D

    2013-01-01

    HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. A proof of concept double-masked randomized controlled study. 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. Simvastatin 40 mg/day or placebo, allocated 1:1. Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065.

  4. Differential Expression of Complement Markers in Normal and AMD Transmitochondrial Cybrids

    Science.gov (United States)

    Nashine, Sonali; Chwa, Marilyn; Kazemian, Mina; Thaker, Kunal; Lu, Stephanie; Nesburn, Anthony; Kuppermann, Baruch D.; Kenney, M. Cristina

    2016-01-01

    Purpose Variations in mitochondrial DNA (mtDNA) and abnormalities in the complement pathways have been implicated in the pathogenesis of age-related macular degeneration (AMD). This study was designed to determine the effects of mtDNA from AMD subjects on the complement pathway. Methods Transmitochondrial cybrids were prepared by fusing platelets from AMD and age-matched Normal subjects with Rho0 (lacking mtDNA) human ARPE-19 cells. Quantitative PCR and Western blotting were performed to examine gene and protein expression profiles, respectively, of complement markers in these cybrids. Bioenergetic profiles of Normal and AMD cybrids were examined using the Seahorse XF24 flux analyzer. Results Significant decreases in the gene and protein expression of complement inhibitors, along with significantly higher levels of complement activators, were found in AMD cybrids compared to Older-Normal cybrids. Seahorse flux data demonstrated that the bioenergetic profiles for Older-Normal and Older-AMD cybrid samples were similar to each other but were lower compared to Young-Normal cybrid samples. Conclusion In summary, since all cybrids had identical nuclei and differed only in mtDNA content, the observed changes in components of complement pathways can be attributed to mtDNA variations in the AMD subjects, suggesting that mitochondrial genome and retrograde signaling play critical roles in this disease. Furthermore, the similar bioenergetic profiles of AMD and Older-Normal cybrids indicate that the signaling between mitochondria and nuclei are probably not via a respiratory pathway. PMID:27486856

  5. Why AMD is a disease of ageing and not of development: mechanisms and insights

    Directory of Open Access Journals (Sweden)

    Kaushal eSharma

    2014-07-01

    Full Text Available Age related macular degeneration (AMD is retinal degenerative disorder which starts with the progression of age. Metabolism plays important role in initiation of ageing related diseases. The cholesterol metabolism components and their oxidized products like 7-ketocholesterol have been shown impact on RPE cells degeneration. These molecules can initiate the mitochondrial apoptotic process and also influenced the complements factors and expression of angiogenic proteins like VEGF etc. In this review we have suggested that AMD is ageing disorder not developmental which has been substantiated with disrupted cholesterol metabolism as described in several age related degenerative diseases.

  6. Public Service Announcement: Do you have AMD?

    Science.gov (United States)

    ... Home Current Issue Past Issues PSA Do you have AMD? Past Issues / Winter 2007 Table of Contents ... this page please turn Javascript on. Do you have AMD? Join the AREDS2 Study! The Age-Related ...

  7. AMD ja ATI kolivad kokku / Kalle Kose

    Index Scriptorium Estoniae

    Kose, Kalle

    2006-01-01

    Maailma suuruselt teise personaalarvutite protsessorite valmistaja Advanced Micro Devices (AMD) liitumisest graafikakaartide tootja ATI Technologies'iga (ATI). Vt. ka: 5 küsimust AMD-le. Küsimustele vastab AMD regiooni esindaja Stockholmis Martin Sjögren

  8. AMD's 64-bit Opteron processor

    CERN Multimedia

    CERN. Geneva

    2003-01-01

    This talk concentrates on issues that relate to obtaining peak performance from the Opteron processor. Compiler options, memory layout, MPI issues in multi-processor configurations and the use of a NUMA kernel will be covered. A discussion of recent benchmarking projects and results will also be included.BiographiesDavid RichDavid directs AMD's efforts in high performance computing and also in the use of Opteron processors...

  9. HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION

    NARCIS (Netherlands)

    Schick, T.; Ersoy, L.; Lechanteur, Y.T.; Saksens, N.T.; Hoyng, C.B.; Hollander, A.I. den; Kirchhof, B.; Fauser, S.

    2016-01-01

    PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information

  10. Introduction to the issue regarding research regarding age related macular degeneration

    Science.gov (United States)

    Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

  11. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants.

    Science.gov (United States)

    Sieving, Paul A; Caruso, Rafael C; Tao, Weng; Coleman, Hanna R; Thompson, Darby J S; Fullmer, Keri R; Bush, Ronald A

    2006-03-07

    Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human CNTF gene and sequestered within capsules that were surgically implanted into the vitreous of the eye. The outer membrane of the encapsulated cell implant is semipermeable to allow CNTF to reach the retina. Ten participants received CNTF implants in one eye. When the implants were removed after 6 months, they contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be therapeutic for retinal degeneration in rcd1 dogs. Although the trial was not powered to form a judgment as to clinical efficacy, of seven eyes for which visual acuity could be tracked by conventional reading charts, three eyes reached and maintained improved acuities of 10-15 letters, equivalent to two- to three-line improvement on standard Snellen acuity charts. A surgically related choroidal detachment in one eye resulted in a transient acuity decrease that resolved with conservative management. This Phase I trial indicated that CNTF is safe for the human retina even with severely compromised photoreceptors. The approach to delivering therapeutic proteins to degenerating retinas using encapsulated cell implants may have application beyond disease caused by genetic mutations.

  12. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...

  13. Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wanjiku Mathenge

    2014-12-01

    Full Text Available Age-related macular degeneration (AMD is a disease of the retina that usually develops in people aged 60 years and older. It affects about 8.7% of the world’s population and is the leading cause of blindness among people aged 50 and older in industrialised countries.

  14. Argon green vs. krypton red laser photocoagulation for extrafoveal choroidal neovascularization secondary to age-related macular degeneration: 3-year results of a multicentre randomized trial. Canadian Ophthalmology Study Group.

    Science.gov (United States)

    Willan, A R; Cruess, A F; Ballantyne, M

    1996-02-01

    To determine whether argon green laser (AGL) or krypton red laser (KRL) is superior for the treatment of well-defined extrafoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) after 3 years of follow-up. Multicentre randomized clinical trial. University-based referral practices in Canada. Among 210 patients selected by ophthalmologists at 13 participating centres there were 191 eligible patients aged 50 years or more with angiographically proven CNV whose posterior edge was 200 to 2500 microns from the foveal avascular zone. Other inclusion criteria included the presence of drusen in either eye, a best corrected visual acuity in the study eye of at least 35 letters on the Early Treatment Diabetic Retinopathy Study chart (equivalent of 20/200 or better on the Snellen chart) and no prior photocoagulation in the study eye. The patients were randomly assigned to receive either AGL (96 patients) or KRL (95 patients) treatment. Treatment with 200-microns spots of 0.2 to 0.5 seconds' exposure to produce a homogeneous grey white lesion that completely covered the CNV. Change from baseline in visual acuity at 1, 2 and 3 years (primary measure), development of persistent or recurrent CNV (secondary measure). There were no significant differences between the treatment groups in drop-out rates. No significant differences were found between the two groups in loss of visual acuity or angiographic evidence of persistent or recurrent CNV. KRL is no better than AGL in preserving vision and preventing loss of visual acuity in patients with AMD with well-defined extrafoveal CNV followed for 3 years.

  15. Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data.

    Science.gov (United States)

    Lee, Aaron Y; Butt, Thomas; Chew, Emily; Agron, Elvira; Clemons, Traci E; Egan, Catherine A; Lee, Cecilia S; Tufail, Adnan

    2018-04-01

    To evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related macular degeneration AMD (nAMD), AREDS category 4. A patient-level health state transition model based on levels of visual acuity in the better-seeing eye was constructed to simulate the costs and consequences of patients taking AREDS vitamin supplements. UK National Health Service (NHS). The model was populated with data from AREDS and real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92 976 ranibizumab treatment episodes. Two treatment approaches were compared: immediate intervention with AREDS supplements or no supplements. quality-adjusted life years (QALYs) and healthcare costs were accrued for each strategy, and incremental costs and QALYs were calculated for the lifetime of the patient. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model. For AREDS category 3, the incremental cost-effectiveness ratio was £30 197. For AREDS category 4 compared with no intervention, AREDS supplements are more effective (10.59 vs 10.43 QALYs) and less costly (£52 074 vs 54 900) over the lifetime of the patient. The recommendation to publicly fund AREDS supplements to category 3 patients would depend on the healthcare system willingness to pay. In contrast, initiating AREDS supplements in AREDS category 4 patients is both cost saving and more effective than no supplement use and should therefore be considered in public health policy. © 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.

  16. Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35.

    Science.gov (United States)

    Chew, Emily Y; Clemons, Traci E; Agrón, Elvira; Sperduto, Robert D; Sangiovanni, John Paul; Kurinij, Natalie; Davis, Matthew D

    2013-08-01

    To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD). Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study. We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study. Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses. Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (≥15 letters). Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (Peffects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases. Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2013 American

  17. Automatic age-related macular degeneration detection and staging

    Science.gov (United States)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  18. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV......Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...... individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single...

  19. Cognitive dysfunction and age-related macular degeneration.

    Science.gov (United States)

    Rozzini, Luca; Riva, Maddalena; Ghilardi, Nausica; Facchinetti, Paola; Forbice, Eliana; Semeraro, Francesco; Padovani, Alessandro

    2014-05-01

    Several previous studies showed that age-related macular degeneration (AMD) and Alzheimer's disease (AD) share common risk factors and histopathology changes, and there is epidemiological evidence linking AMD to cognitive impairment. We tested this theory in 51 patients with late-stage AMD and 24 controls by analyzing their neuropsychological profiles. In this study, data showed that patients affected by late-stage AMD have a worse global cognitive function than those of the controls and, in particular, show worse performances in memory tasks. Moreover, patients affected by the dry form of AMD are significantly impaired in executive functions in addition to memory. Data support the hypothesis of a possible association between AMD and cognitive impairment. In particular, patients affected by the dry form of AMD may be at greater risk of developing subsequent dementia.

  20. Gene-diet interactions in age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

  1. Nutritional modulation of age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  2. Prevalence of Age-Related Macular Degeneration in Europe

    NARCIS (Netherlands)

    Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Hoyng, Carel B.; Kersten, Eveline; Kilger, Ellen; Langen, Hanno; Lengyel, Imre; Luthert, Phil; Maugeais, Cyrille; Meester-Smoor, Magda; Monés, Jordi; Nogoceke, Everson; Peto, Tunde; Pool, Frances M.; Rodríguez, Eduardo; Ueffing, Marius; Ulrich Bartz-Schmidt, Karl U.; van Leeuwen, Elisabeth M.; Verzijden, Timo; Zumbansen, Markus; Acar, Niyazi; Anastosopoulos, Eleftherios; Azuara-Blanco, Augusto; Bergen, Arthur; Binquet, Christine; Bird, Alan; Brétillon, Lionel; Buitendijk, Gabrielle; Cachulo, Maria Luz; Chakravarthy, Usha; Chan, Michelle; Chang, Petrus; Colijn, Johanna; Cumberland, Philippa; Cunha-Vaz, José; Daien, Vincent; Deak, Gabor; Delyfer, Marie-Noëlle; den Hollander, Anneke; Dietzel, Martha; Erke, Maja Gran; Fauser, Sascha; Finger, Robert; Fletcher, Astrid; Foster, Paul; Founti, Panayiota; Göbel, Arno; Gorgels, Theo; Grauslund, Jakob; Grus, Franz; Hammond, Christopher; Helmer, Catherine; Hense, Hans-Werner; Hermann, Manuel; Hoehn, René; Hogg, Ruth; Holz, Frank; Hoyng, Carel; Jansonius, Nomdo; Janssen, Sarah; Khawaja, Anthony; Klaver, Caroline; Lamparter, Julia; Le Goff, Mélanie; Leal, Sergio; Lechanteur, Yara; Lehtimäki, Terho; Lotery, Andrew; Leung, Irene; Mauschitz, Matthias; Merle, Bénédicte; Meyer Zu Westrup, Verena; Midena, Edoardo; Miotto, Stefania; Mirshahi, Alireza; Mohan-Saïd, Sadek; Mueller, Michael; Muldrew, Alyson; Nunes, Sandrina; Oexle, Konrad; Rahi, Jugnoo; Raitakari, Olli; Ribeiro, Luisa; Rougier, Marie-Bénédicte; Sahel, José; Salonikiou, Aggeliki; Sanchez, Clarisa; Schmitz-Valckenberg, Steffen; Schweitzer, Cédric; Shehata, Jasmin; Silvestri, Giuliana; Simader, Christian; Souied, Eric; Springelkamp, Henriet; Tapp, Robyn; Verhoeven, Virginie; Von Hanno, Therese; Vujosevic, Stela; Williams, Katie; Wolfram, Christian; Yip, Jennifer; Zerbib, Jennyfer; Zwiener, Isabella

    2017-01-01

    Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

  3. Prevalence of Age-Related Macular Degeneration in Europe

    DEFF Research Database (Denmark)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

    2017-01-01

    PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...

  4. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  5. Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

    Science.gov (United States)

    Agarwal, Aniruddha; Rhoades, William R; Hanout, Mostafa; Soliman, Mohamed Kamel; Sarwar, Salman; Sadiq, Mohammad Ali; Sepah, Yasir Jamal; Do, Diana V; Nguyen, Quan Dong

    2015-01-01

    Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. PMID:26089632

  6. Association of Htra1 Gene Polymorphisms with the Risk of Developing AMD in Iranian Population

    Directory of Open Access Journals (Sweden)

    Mohammad Askari

    2015-10-01

    Full Text Available Background: Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD. This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature requirement A-1 (HTRA1 gene polymorphisms with the risk of developing AMD in the Iranian population. Methods: Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. Results: Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. Conclusions: The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population

  7. Association of Htra1 gene polymorphisms with the risk of developing AMD in Iranian population.

    Science.gov (United States)

    Askari, Mohammad; Nikpoor, Amin Reza; Gorjipour, Fazel; Mazidi, Mohsen; Sanati, Mohammad Hosein; Aryan, Hajar; Irani, Alireza; Ghasemi Falavarjani, Khalil; Nazari, Hossein; Mousavizadeh, Kazem

    2015-10-01

    Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature ‎requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population. Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population.

  8. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration

    NARCIS (Netherlands)

    Augood, Cristina; Chakravarthy, Usha; Young, Ian; Vioque, Jesus; de Jong, Paulus T. V. M.; Bentham, Graham; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vingerling, Johannes R.; Fletcher, Astrid E.

    2008-01-01

    Fish intake, the major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may reduce the risk of age-related macular degeneration (AMD). We investigated the association of oily fish and dietary DHA and EPA with neovascular AMD (NV-AMD). Participants aged >/=65 y in the

  9. Involvement of a gut-retina axis in protection against dietary glycemia induced age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial cell (RPE) dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns on risk for AMD, but th...

  10. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  11. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  12. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  13. Comparing humans and deep learning performance for grading AMD: A study in using universal deep features and transfer learning for automated AMD analysis.

    Science.gov (United States)

    Burlina, Philippe; Pacheco, Katia D; Joshi, Neil; Freund, David E; Bressler, Neil M

    2017-03-01

    When left untreated, age-related macular degeneration (AMD) is the leading cause of vision loss in people over fifty in the US. Currently it is estimated that about eight million US individuals have the intermediate stage of AMD that is often asymptomatic with regard to visual deficit. These individuals are at high risk for progressing to the advanced stage where the often treatable choroidal neovascular form of AMD can occur. Careful monitoring to detect the onset and prompt treatment of the neovascular form as well as dietary supplementation can reduce the risk of vision loss from AMD, therefore, preferred practice patterns recommend identifying individuals with the intermediate stage in a timely manner. Past automated retinal image analysis (ARIA) methods applied on fundus imagery have relied on engineered and hand-designed visual features. We instead detail the novel application of a machine learning approach using deep learning for the problem of ARIA and AMD analysis. We use transfer learning and universal features derived from deep convolutional neural networks (DCNN). We address clinically relevant 4-class, 3-class, and 2-class AMD severity classification problems. Using 5664 color fundus images from the NIH AREDS dataset and DCNN universal features, we obtain values for accuracy for the (4-, 3-, 2-) class classification problem of (79.4%, 81.5%, 93.4%) for machine vs. (75.8%, 85.0%, 95.2%) for physician grading. This study demonstrates the efficacy of machine grading based on deep universal features/transfer learning when applied to ARIA and is a promising step in providing a pre-screener to identify individuals with intermediate AMD and also as a tool that can facilitate identifying such individuals for clinical studies aimed at developing improved therapies. It also demonstrates comparable performance between computer and physician grading. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Visual acuity outcomes after cataract surgery in patients with age-related macular degeneration: age-related eye disease study report no. 27.

    Science.gov (United States)

    Forooghian, Farzin; Agrón, Elvira; Clemons, Traci E; Ferris, Frederick L; Chew, Emily Y

    2009-11-01

    To evaluate visual acuity outcomes after cataract surgery in patients with varying degrees of age-related macular degeneration (AMD). Cohort study. A total of 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), a prospective, multicenter, epidemiological study of the clinical course of cataract and AMD and a randomized controlled trial of antioxidants and minerals. Standardized lens and fundus photographs, performed at baseline and annual visits, were graded by a centralized reading center using standardized protocols for severity of AMD and lens opacities. History of cataract surgery was obtained every 6 months. Analyses were conducted using multivariate logistic regression. The change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. Visual acuity results were analyzed for 1939 eyes that had cataract surgery during AREDS. The mean time from cataract surgery to measurement of postoperative BCVA was 6.9 months. After adjustment for age at surgery, gender, type, and severity of cataract, the mean change in visual acuity at the next study visit after the cataract surgery was as follows: Eyes without AMD gained 8.4 letters of acuity (P<0.0001), eyes with mild AMD gained 6.1 letters of visual acuity (P<0.0001), eyes with moderate AMD gained 3.9 letters (P<0.0001), and eyes with advanced AMD gained 1.9 letters (P = 0.04). The statistically significant gain in visual acuity after cataract surgery was maintained an average of 1.4 years after cataract surgery. On average, participants with varying severity of AMD benefited from cataract surgery with an increase in visual acuity postoperatively. This average gain in visual acuity persisted for at least 18 months.

  15. Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.

    Science.gov (United States)

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.

  16. Anti vascular endothelial growth factor sequential therapy for neovascular age-related macular degeneration: is this the new deal?

    Science.gov (United States)

    Neri, Piergiorgio; Mariotti, Cesare; Arapi, Ilir; Bambini, Elisa; Giovannini, Alfonso

    2012-03-01

    To review clinical data on the sequential use of the non-selective vascular endothelial growth factor (VEGF) inhibitors (ranibizumab and bevacizumab) and the selective VEGF inhibitor (pegaptanib) in the treatment of neovascular age related macular degeneration (n-AMD). This is a selective review of the literature based on a PubMed search using the terms 'age-related macular degeneration', 'selective anti-VEGF', 'non-selective anti-VEGF' and 'combination therapy' from 2000 to date in the English language. Studies on the management of n-AMD reporting adherence, patient-reported outcomes, costs, side effects, resource use and cost effectiveness were also included. The trial data suggest that pan-VEGF inhibition provides improved treatment outcomes in patients with n-AMD with selective anti-VEGF agents offering better tolerability on long-term treatment. A pilot trial and a large-scale, multicentre study confirmed the long-term efficacy of a selective VEGF inhibitor when used as maintenance therapy. Importantly, there is evidence that selective VEGF inhibition also reduces the risks associated with pan-VEGF blockade in patients with n-AMD. Anti-VEGF agents play a principal role in the management of n-AMD. The most potent are the pan-VEGF agents although there is some discussion regarding their long-term tolerability. The sequential use of non-selective VEGF inhibitors as booster therapy with a selective VEGF inhibitor as maintenance therapy seems to offer a promising safety/efficacy profile, as well as improved cost/effectiveness.

  17. Ginkgo biloba extract for age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R

    2013-01-31

    Ginkgo is used in the treatment of peripheral vascular disease and 'cerebral insufficiency'. It is thought to have several potential mechanisms of action including increased blood flow, platelet activating factor antagonism, and prevention of membrane damage caused by free radicals. Vascular factors and oxidative damage are thought to be two potential mechanisms in the pathology of age-related macular degeneration (AMD). The objective of this review was to determine the effect of Ginkgo biloba extract on the progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2012), EMBASE (January 1980 to October 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to October 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2012. We searched the reference lists of identified reports and the Science Citation Index. We also contacted investigators of included studies for additional information. All randomised trials in people with AMD where Ginkgo biloba extract had been compared to control were included. The review author extracted data using a standardised form. The data were verified with the trial investigators. Trial quality was assessed. Two published trials were identified that randomised a total of 119 people. In one study conducted in France, 20 people were randomly allocated to Gingko biloba extract EGb 761 80 mg twice daily or placebo. In

  18. In vitro circumvention of cisplatin resistance by the novel sterically hindered platinum complex AMD473.

    Science.gov (United States)

    Holford, J.; Sharp, S. Y.; Murrer, B. A.; Abrams, M.; Kelland, L. R.

    1998-01-01

    A novel sterically hindered platinum complex, AMD473 [cis-aminedichloro(2-methylpyridine) platinum (II)], has been selected for phase I clinical trials due to commence in 1997. AMD473 was rationally designed to react preferentially with nucleic acids over sulphur ligands such as glutathione. This report documents the in vitro circumvention of acquired cisplatin resistance mechanisms in human ovarian carcinoma (HOC) cell lines by AMD473. In a panel of 11 HOC cell lines, AMD473 showed intermediate growth inhibition potency (mean IC50 of 8.1 microM) in comparison to cisplatin (mean IC50 of 2.6 microM) and carboplatin (mean IC50 of 20.3 microM). AMD473 showed only a 30.7-fold increase in IC50 value from the most sensitive to the most resistant HOC cell line, whereas for cisplatin it was 117.9-fold and for carboplatin 119.7-fold. AMD473 also showed significantly (P or = 14 h for AMD473) after equitoxic doses were exposed to HOC cells for 2 h. AMD473 ICLs in the CH1 HOC cell line were slowly formed and showed no visible signs of being repaired 24 h after removal of drug. This was paralleled by a slower, longer lasting induction of p53 protein by equitoxic doses of AMD473 in HOC cell lines with wild-type p53. This new class of sterically hindered platinum compound, selected for clinical trial in 1997, may therefore elicit improved clinical response in intrinsically and acquired cisplatin-resistant tumours in the clinic. Images Figure 9 PMID:9472630

  19. Update on the role of genetics in the onset of age-related macular degeneration

    Science.gov (United States)

    Francis, Peter James; Klein, Michael L

    2011-01-01

    Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century. PMID:21887094

  20. Molecular pharmacodynamics of emixustat in protection against retinal degeneration.

    Science.gov (United States)

    Zhang, Jianye; Kiser, Philip D; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P; Palczewski, Krzysztof

    2015-07-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators.

  1. Fish Consumption and Age-Related Macular Degeneration Incidence: A Meta-Analysis and Systematic Review of Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    2016-11-01

    Full Text Available The association between fish consumption and risk of age-related macular degeneration (AMD is still unclear. The aim of the current meta-analysis and systematic review was to quantitatively evaluate findings from observational studies on fish consumption and the risk of AMD. Relevant studies were identified by searching electronic databases (Medline and EMBASE and reviewing the reference lists of relevant articles up to August, 2016. Prospective cohort studies that reported relative risks (RRs and 95% confidence intervals (CIs for the link between fish consumption and risk of AMD were included. A total of 4202 cases with 128,988 individuals from eight cohort studies were identified in the current meta-analysis. The meta-analyzed RR was 0.76 (95% CI, 0.65–0.90 when any AMD was considered. Subgroup analyses by AMD stages showed that fish consumption would reduce the risk of both early (RR, 0.83; 95% CI, 0.72–0.96 and late (RR; 0.76; 95% CI, 0.60–0.97 AMD. When stratified by the follow-up duration, fish consumption was a protective factor of AMD in both over 10 years (n = 5; RR, 0.81; 95% CI, 0.67–0.97 and less than 10 years (n = 3; RR, 0.70; 95% CI, 0.51 to 0.97 follow-up duration. Stratified analyses by fish type demonstrated that dark meat fish (RR, 0.68, 95% CI, 0.46–0.99, especially tuna fish (RR, 0.58; 95% CI, 95% CI, 0.47–0.71 intake was associated with reduced AMD risk. Evidence of a linear association between dose of fish consumption and risk of AMD was demonstrated. The results of this meta-analysis demonstrated that fish consumption can reduce AMD risk. Advanced, well-designed, randomized clinical trials are required in order to validate the conclusions in this study.

  2. Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

    Science.gov (United States)

    Folgar, Francisco A; Yuan, Eric L; Sevilla, Monica B; Chiu, Stephanie J; Farsiu, Sina; Chew, Emily Y; Toth, Cynthia A

    2016-01-01

    To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD). Prospective, observational study. Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study. High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA). Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years

  3. Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Querques G

    2011-05-01

    Full Text Available Giuseppe Querques¹, Fernando Onofrio Avellis1,2, Lea Querques1,3, Francesco Bandello³, Eric H Souied¹ ¹Service d'Ophtalmologie, Centre Hospitalier Intercommunal Créteil, Université Paris-Est Créteil, Créteil, France; ²Parma Eye Clinic University Hospital, Università degli Studi di Parma, Parma, Italy; ³Department of Ophthalmology, Università Vita-Salute San Raffaele Milano, Milano, Italy Date of preparation: March 3, 2011 Conflict of interest: None declaredClinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD?Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches.Implementation: strategy of administration, safety of intravitreal injectionKeywords: age-related macular degeneration, antivascular endothelial growth factor, choroidal neovascularization, drusen, geographic atrophy

  4. Lutein and Zeaxanthin—Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection

    Science.gov (United States)

    Eisenhauer, Bronwyn; Natoli, Sharon; Liew, Gerald; Flood, Victoria M.

    2017-01-01

    Lutein and zeaxanthin (L/Z) are the predominant carotenoids which accumulate in the retina of the eye. The impact of L/Z intake on the risk and progression of age-related macular degeneration (AMD), a leading cause of blindness in the developed world, has been investigated in cohort studies and clinical trials. The aims of this review were to critically examine the literature and evaluate the current evidence relating to L/Z intake and AMD, and describe important food sources and factors that increase the bioavailability of L/Z, to inform dietary models. Cohort studies generally assessed L/Z from dietary sources, while clinical trials focused on providing L/Z as a supplement. Important considerations to take into account in relation to dietary L/Z include: nutrient-rich sources of L/Z, cooking methods, diet variety and the use of healthy fats. Dietary models include examples of how suggested effective levels of L/Z can be achieved through diet alone, with values of 5 mg and 10 mg per day described. These diet models depict a variety of food sources, not only from dark green leafy vegetables, but also include pistachio nuts and other highly bioavailable sources of L/Z such as eggs. This review and the diet models outlined provide information about the importance of diet variety among people at high risk of AMD or with early signs and symptoms of AMD. PMID:28208784

  5. Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.

    Science.gov (United States)

    Wu, Juan; Cho, Eunyoung; Willett, Walter C; Sastry, Srinivas M; Schaumberg, Debra A

    2015-12-01

    Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated. To investigate the associations between intakes of carotenoids and AMD. Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63,443 women and 38,603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline. Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined. We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend carotenoids, either as predicted plasma score or calculated intake, with

  6. Association of OCT derived drusen measurements with AMD associated-genotypic SNPs in Amish population.

    Science.gov (United States)

    Chavali, Venkata Ramana Murthy; Diniz, Bruno; Huang, Jiayan; Ying, Gui-Shuang; Sadda, SriniVas R; Stambolian, Dwight

    To investigate the association of OCT derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration. Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High- Definition-OCT. Measurements were obtained in the macula region within a central circle (CC) of 3 mm diameter and a surrounding perifoveal ring (PR) of 3 to 5 mm diameter using the Cirrus OCT RPE analysis software. Other demographic information including age, gender and smoking status were collected. Study subjects were further genotyped to determine their risk for the AMD associated SNPs in SYN3, LIPC, ARMS2, C3, CFB, CETP, CFI and CFH genes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models. 432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status) confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for drusen area (area increased 0.12 mm 2 for a risk allele increase, pAmish AMD population.

  7. Association of OCT-Derived Drusen Measurements with AMD-Associated Genotypic SNPs in the Amish Population

    OpenAIRE

    Chavali, Venkata Ramana Murthy; Diniz, Bruno; Huang, Jiayan; Ying, Gui-Shuang; Sadda, SriniVas R.; Stambolian, Dwight

    2015-01-01

    Purpose: To investigate the association of optical coherence tomography (OCT)-derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration. Methods: Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High-Definition OCT. Measurements were obtained in the macula region within a central circle (CC) of 3...

  8. Prevalence of anti-retinal autoantibodies in different stages of Age-related macular degeneration.

    Science.gov (United States)

    Adamus, Grazyna; Chew, Emily Y; Ferris, Frederick L; Klein, Michael L

    2014-12-08

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults. Anti-retinal autoantibodies (AAbs) have been found in individuals with AMD. The goal of the study was to determine the AAb specificity in different stages of AMD, and determine whether there is a prevalent AAb signature. Sera of 134 participants in the Age-related Eye Disease Study were analyzed for anti-retinal AAbs by western blotting. The subjects were classified by diagnostic subgroups based upon their clinical classification: No AMD, Intermediate AMD, and Late AMD - geographic atrophy (GA) and Late AMD - neovascular (NV). The presence of anti-retinal AAb was detected in 58% patients with Intermediate and Late AMD, and 54% of those with no AMD. AAbs bound to fifteen different retinal antigens. Most individuals had 1 specific AAbs (67%), with the remainder having 2 to 4 different AAbs. Over 40% of patients with Intermediate AMD, and 46% of those with GA had anti-enolase AAbs, compared with 29% of individuals with NV and 29% with no AMD. Different AAbs signatures related to NV as compared to GA and/or Intermediate AMD were distinguished. Anti-40-kDa (10%) and 42-kDa (16%) autoantibodies were associated with Intermediate AMD, while anti-30-kDa AAbs (23%) were primarily present in GA. Anti-32-kDa (12%), 35-kDa (21%), and 60-kDa (8%) AAbs were more frequent in NV AMD. A unique AAb pattern for each of the disease subgroups was present when AMD progressed from the intermediate to the late forms of severity. Differences in the frequency of specific AAbs between AMD subgroups suggested that they may participate in pathogenicity of AMD. Further studies are necessary to confirm these observations in the larger cohort and individual AMD patients over time.

  9. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages.

    Science.gov (United States)

    Schick, Tina; Altay, Lebriz; Viehweger, Eva; Hoyng, Carel B; den Hollander, Anneke I; Felsch, Moritz; Fauser, Sascha

    2016-01-01

    Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed pstages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients.

  10. Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

    Directory of Open Access Journals (Sweden)

    Agarwal A

    2015-06-01

    Full Text Available Aniruddha Agarwal, William R Rhoades, Mostafa Hanout, Mohamed Kamel Soliman, Salman Sarwar, Mohammad Ali Sadiq, Yasir Jamal Sepah, Diana V Do, Quan Dong Nguyen Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA Abstract: Contemporary management of neovascular age-related macular degeneration (AMD has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. Keywords: AMD, neovascular AMD, choroidal neovascular membrane, pharmacogenomics, VEGF, low-vision rehabilitation, gene therapy

  11. Prevention of Age-Related Macular Degeneration.

    Science.gov (United States)

    Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; V, Jayprakash; Raman, Rajiv

    2017-01-01

    Age-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  12. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  13. The incidence of adjacent segment degeneration after cervical disc arthroplasty (CDA: a meta analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Baohui Yang

    Full Text Available Cervical disc arthroplasty is being used as an alternative degenerative disc disease treatment with fusion of the cervical spine in order to preserve motion. However, whether replacement arthoplasty in the spine achieves its primary patient centered objective of lowering the frequency of adjacent segment degeneration is not verified yet.We conducted a meta-analysis according to the guidelines of the Cochrane Collaboration using databases including PubMed, Cochrane Central Register of Controlled Trials and Embase. The inclusion criteria were: 1 Randomized, controlled study of degenerative disc disease of the cervical spine involving single segment or double segments using Cervical disc arthroplasty (CDA with anterior cervical discectomy and fusion (ACDF as controls; 2 A minimum of two-year follow-up using imaging and clinical analyses; 3 Definite diagnostic evidences for "adjacent segment degeneration" and "adjacent segment disease"; 4 At least a minimum of 30 patients per population. Two authors independently selected trials; assessed methodological quality, extracted data and the results were pooled.No study has specifically compared the results of adjacent segment degenerative; Two papers describing 140 patients with 162 symptomatic cervical segment disorders and compared the rate of postoperative adjacent segment disease development between CDA and ACDF treatments, three publications describing the rate of adjacent-segment surgery including 1273 patients with symptomatic cervical segments. The result of the meta-analysis indicates that there were fewer the rate of adjacent segment disease and the rate for adjacent-segment surgery comparing CDA with ACDF, but the difference was not statistically significant.Based on available evidence, it cannot be concluded, that CDA can significantly reduce the postoperative rate of the adjacent segment degenerative and adjacent segment disease. However, due to some limitations, the results of this meta

  14. Age-related Macular Degeneration: Current concepts in ...

    African Journals Online (AJOL)

    Sheri

    In Nigeria, ophthalmologists should run a randomized trial using bevacizumab; if the results are positive, the. Minimally classic/occult trial of the Anti-VEGF antibody. *. Ranibizumab In the Treatment of Neovascular AMD. ANti-VEGF antibody for the treatment of predominantly classic. ** choroidal neovascularization in AMD.

  15. Lutein and Zeaxanthin?Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection

    OpenAIRE

    Eisenhauer, Bronwyn; Natoli, Sharon; Liew, Gerald; Flood, Victoria M.

    2017-01-01

    Lutein and zeaxanthin (L/Z) are the predominant carotenoids which accumulate in the retina of  the eye. The impact of L/Z intake on the risk and progression of age‐related macular degeneration (AMD),  a leading cause of blindness in the developed world, has been investigated in cohort studies and clinical  trials. The aims of this review were to critically examine the literature and evaluate the current evidence  relating to L/Z intake and AMD, and describe important food sources and factors ...

  16. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration

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    Toshiyuki Matsuura

    2017-01-01

    Full Text Available Purpose. To compare serum levels of malondialdehyde (MDA in patients with wet age-related macular degeneration (wAMD, patients with dry AMD (dAMD, and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group, and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

  17. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study.

    Science.gov (United States)

    Sangiovanni, John Paul; Agrón, Elvira; Meleth, A Dhananjayan; Reed, George F; Sperduto, Robert D; Clemons, Traci E; Chew, Emily Y

    2009-12-01

    omega-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD). We investigated whether omega-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD. We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on omega-3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit. Participants who reported the highest omega-3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P reporting the highest consumption of omega-3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.

  18. Optical Coherence Tomography Monitoring Strategies for A-VEGF-Treated Age-Related Macular Degeneration: An Evidence-Based Analysis.

    Science.gov (United States)

    Pron, G

    2014-01-01

    New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals' AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients. Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored in longitudinal follow-up. Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and

  19. Optical Coherence Tomography Monitoring Strategies for A-VEGF—Treated Age-Related Macular Degeneration: An Evidence-Based Analysis

    Science.gov (United States)

    Pron, G

    2014-01-01

    Background New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti–vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals’ AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. Objectives To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF–treated neovascular AMD (n-AMD) patients. Data Sources Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF–treated n-AMD patients monitored in longitudinal follow-up. Review Methods Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. Results A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF–treated n-AMD. These

  20. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320. The ocular surface temperature (OST of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272. OST in AMD patients was significantly lower than in controls (P>0.05. Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  1. Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)

    DEFF Research Database (Denmark)

    Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I

    2012-01-01

    To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD).......To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD)....

  2. MACULAR DEGENERATION AND ASPIRIN USE.

    Science.gov (United States)

    Small, Kent W; Garabetian, Christine A; Shaya, Fadi S

    2017-09-01

    To review current literature of the benefits that aspirin provides for patients' cardiovascular health compared with the risk of AMD worsening. We performed a review and critically analyzed six cardiovascular and four ophthalmological trials regarding risks and benefits of aspirin use. The prospective randomized cardiovascular trials had a cumulative 167,580 while the 3 smaller ophthalmological data sets had a cumulative 12,015 subjects. The reviewed meta-analysis literature demonstrated a statistically significant 32% reduction in the risk of nonfatal stroke with regular aspirin users. The study also documented that aspirin users decreased the risk of fatal vascular deaths by 15%. Of the three ophthalmological studies highlighting the adverse affects of aspirin association with AMD, all suggested an exacerbation of AMD without statistical significance and broad confidence bands. Overall, the number, size, and quality of the cardiovascular studies recommending aspirin use are far superior to the fewer, smaller and conflicting studies suggesting a possible adverse effect of aspirin use in relation to AMD. The benefits of aspirin usage include preserving the duration and quality of life by decreasing stroke and heart attack risk. These benefits seem to far outweigh the theoretical risks of possibly exacerbating wet AMD, which can be reasonably controlled with anti-VEGF therapy.

  3. Effect of Supplemental Lutein and Zeaxanthin on Serum, Macular Pigmentation, and Visual Performance in Patients with Early Age-Related Macular Degeneration

    Science.gov (United States)

    Huang, Yang-Mu; Dou, Hong-Liang; Huang, Fei-Fei; Xu, Xian-Rong; Zou, Zhi-Yong

    2015-01-01

    Purpose. To compare the 2-year effect of multiple doses of lutein/zeaxanthin on serum, macular pigmentation, and visual performance on patients with early age-related macular degeneration (AMD). Methods. In this randomized, double-blinded, and placebo-controlled trial, 112 early AMD patients randomly received either 10 mg lutein, 20 mg lutein, a combination of lutein (10 mg) and zeaxanthin (10 mg), or placebo daily for 2 years. Serum concentration of lutein/zeaxanthin, macular pigment optical density (MPOD), visual functions including best-spectacle corrected visual acuity (BCVA), contrast sensitivity (CS), flash recovery time (FRT), and vision-related quality of life (VFQ25) was quantified. Results. Serum lutein concentration and MPOD significantly increased in all the active treatment groups. Supplementation with 20 mg lutein was the most effective in increasing MPOD and CS at 3 cycles/degree for the first 48 weeks. However, they both significantly increased to the same peak value following supplementation with either 10 mg or 20 mg lutein during the intervention. No statistical changes of BCVA or FRT were observed during the trial. Conclusions. Long-term lutein supplementation could increase serum lutein concentration, MPOD, and visual sensitivities of early AMD patients. 10 mg lutein daily might be an advisable long-term dosage for early AMD treatment. PMID:25815324

  4. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    NARCIS (Netherlands)

    Schick, T.; Altay, L.; Viehweger, E.; Hoyng, C.B.; Hollander, A.I. den; Felsch, M.; Fauser, S.

    2016-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic

  5. Immunological Factors in the Pathogenesis and Treatment of Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Kijlstra, A.; Heij, La E.C.; Hendrikse, F.

    2005-01-01

    Recent findings indicate that immunological factors are involved not only in the pathogenesis of age-related macular degeneration (AMD), but also in its treatment. Earlier data showing the presence of inflammatory cells in affected areas of AMD retinas support this statement. Although a possible

  6. The association between Neovascular Age-related Macular Degeneration and Regulatory T cells in peripheral blood

    DEFF Research Database (Denmark)

    Madelung, Christopher Fugl; Falk, Mads; Sørensen, Torben Lykke

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were...

  7. Cardiovascular risk factors associated with age-related macular degeneration: the Tromso Study

    DEFF Research Database (Denmark)

    Erke, M. G.; Bertelsen, G.; Peto, T.

    2014-01-01

    PurposeTo examine associations between cardiovascular risk factors and age-related macular degeneration (AMD). MethodsA population-based, cross-sectional study of Caucasians aged 65-87years was conducted in Norway in 2007/2008. Retinal photographs were graded for AMD. Multivariable logistic...

  8. Cataract surgery and age-related macular degeneration. An evidence-based update

    DEFF Research Database (Denmark)

    Kessel, Line; Erngaard, Ditte; Flesner, Per

    2015-01-01

    PURPOSE: Age-related macular degeneration (AMD) and cataract often coexist in patients and concerns that cataract surgery is associated with an increased risk of incidence or progression of existing AMD has been raised. This systematic review and meta-analysis is focused on presenting the evidence...

  9. Clinical characteristics of familial and sporadic age-related macular degeneration: differences and similarities

    NARCIS (Netherlands)

    Saksens, N.T.M.; Kersten, E.; Groenewoud, J.M.M.; Grinsven, M.J.J.P. van; Ven, J.P.H. van de; Sanchez, C.I.; Schick, T.; Fauser, S.; Hollander, A.I. den; Hoyng, C.B.; Boon, C.J.F.

    2014-01-01

    PURPOSE: We describe the differences and similarities in clinical characteristics and phenotype of familial and sporadic patients with age-related macular degeneration (AMD). METHODS: We evaluated data of 1828 AMD patients and 1715 controls enrolled in the European Genetic Database. All subjects

  10. Prevalence of age-related macular degeneration in the United States

    NARCIS (Netherlands)

    Friedman, David S.; O'Colmain, Benita J.; Muñoz, Beatriz; Tomany, Sandra C.; McCarty, Cathy; de Jong, Paulus T. V. M.; Nemesure, Barbara; Mitchell, Paul; Kempen, John

    2004-01-01

    To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in

  11. Visual acuity after cataract surgery in patients with age-related macular degeneration: age-related eye disease study 2 report number 5.

    Science.gov (United States)

    Huynh, Nancy; Nicholson, Benjamin P; Agrón, Elvira; Clemons, Traci E; Bressler, Susan B; Rosenfeld, Philip J; Chew, Emily Y

    2014-06-01

    To evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD). Cohort study. A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD. Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6-month telephone calls. Analyses were conducted using multivariate repeated-measures regression. Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n = 30) gained 11.2 letters (95% confidence interval [CI], 6.9-15.5), eyes with moderate AMD (n = 346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n = 462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with noncentral geographic atrophy (n = 70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n = 324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (P < 0.0001). Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier

  12. Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

    Science.gov (United States)

    Daniel, Ebenezer; Shaffer, James; Ying, Gui-shuang; Grunwald, Juan E; Martin, Daniel F; Jaffe, Glenn J; Maguire, Maureen G

    2016-03-01

    To compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Patients with NVAMD. Reading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra-retinal leakage of fluorescein in combination with other associated features. Visual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years. Retinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P treatment in CATT, eyes with RAP were less likely to have fluid, FA leakage, scar, and SHRM and more likely to have GA than eyes without RAP. Mean improvement in VA was similar at 2 years. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. Lipids, Lipoproteins, and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Katayoon B. Ebrahimi

    2011-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. A prominent age-related change is the accumulation of neutral lipid in normal Bruch's membrane (BrM throughout adulthood and also disease-related BrM accumulations called basal deposits and drusen. AMD lesion formation has thus been conceptualized as sharing mechanisms with atherosclerotic plaque formation, where low-density lipoprotein (LDL retention within the arterial wall initiates a cascade of pathologic events. However, we do not yet understand how lipoproteins contribute to AMD. This paper explores how systemic and local production of lipoproteins might contribute to the pathogenesis of AMD.

  14. Variations in Treatment Delivery for Patients with Neovascular AMD in the UK: Results from an Ophthalmology Trainee Clinical Research Network Study.

    Science.gov (United States)

    Hanumunthadu, Daren; Nowak, Victoria A; Hassan, Farida; Hossain, Ibtesham; Patel, Darshak S; Hamidovic, Lamia; Abdulhussein, Dalia; Hausien, Isra; Papamichael, Esther; Arunakirinathan, Meena; Quijano, Claudia; George, Sheena; Patel, Praveen J

    2017-12-01

    The aim of this study was to determine treatment delivery patterns for patients with neovascular age-related macular degeneration (nAMD) across the UK through an ophthalmology trainee research network delivered observational study. Data were collected via an online tool by potential research collaborators identified by the Ophthalmology Trainee Clinical Trial Network (OCTN). Collaborators were asked to comment on periprocedural practices of treatment of nAMD in their eye unit including treatment location and injectors, clinical assessment and routine observation in patients undergoing intravitreal treatment. Data were available from 26 units around the United Kingdom. Survey methodology refinement was approximately 3 months, and the average response time was 4.9 ± 2.4 days. The majority of responders confirmed that treatment was undertaken as a "one-stop" service (n = 15, 58%), delivered in a clean room (n = 23, 88%). In the majority of units, doctors administered injections (n = 24, 92%), but significant treatment was also given by nurse injectors (n = 21, 81%). All collaborators reported that patients underwent visual acuity testing and optical coherence tomography imaging at all visits, but other imaging including fundus fluorescein angiography (FFA) did not take place in all cases (n = 17, 65%) and only at baseline visit. These results demonstrate the feasibility of conducting ophthalmology trainee led and delivered observational studies. Our results show that FFA is not routinely used in the diagnosis of nAMD in the units sampled; most injections are carried out in a clean room, and ophthalmic nurses delivering injections is a highly prevalent model of care in the UK.

  15. Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab

    Science.gov (United States)

    Meyer, C H; Holz, F G

    2011-01-01

    Three anti-vascular endothelial growth factor (VEGF) therapies are currently used for the treatment of patients with wet age-related macular degeneration (AMD): pegaptanib, ranibizumab, and bevacizumab. Ranibizumab is an antibody fragment approved for the treatment of wet AMD. Bevacizumab is a full-length antibody registered for use in oncology but unlicensed for wet AMD. However, it is used off-label worldwide not only for wet AMD but also for various other ocular diseases associated with macular edema and abnormal vessel growth. We consider aspects of ranibizumab and bevacizumab in relation to their molecular characteristics, in vitro and in vivo properties, and preclinical safety data. Before 2009, most studies described the short-term toxicity of bevacizumab in multiple cell types of the eye. Since 2009, an increasing number of studies have compared the properties of ranibizumab and bevacizumab and investigated their impact on retinal cell functioning. Compared with bevacizumab, ranibizumab neutralizes VEGF better at low concentrations, maintains efficacy for longer, and has a higher retinal penetration and potency. Studies in animals demonstrate ranibizumab to be better localized to the injected eye, whereas bevacizumab appears to have a greater effect in the fellow eye. In humans, a localized and systemic effect has been reported for both molecules. In conclusion, overlapping yet distinct pharmacological properties of ranibizumab and bevacizumab indicate that safety or efficacy data from one cannot be extrapolated to the other. PMID:21455242

  16. Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

    Science.gov (United States)

    Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

    2010-03-01

    The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

  17. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.

    Science.gov (United States)

    Mitter, Sayak K; Song, Chunjuan; Qi, Xiaoping; Mao, Haoyu; Rao, Haripriya; Akin, Debra; Lewin, Alfred; Grant, Maria; Dunn, William; Ding, Jindong; Bowes Rickman, Catherine; Boulton, Michael

    2014-01-01

    Autophagic dysregulation has been suggested in a broad range of neurodegenerative diseases including age-related macular degeneration (AMD). To test whether the autophagy pathway plays a critical role to protect retinal pigmented epithelial (RPE) cells against oxidative stress, we exposed ARPE-19 and primary cultured human RPE cells to both acute (3 and 24 h) and chronic (14 d) oxidative stress and monitored autophagy by western blot, PCR, and autophagosome counts in the presence or absence of autophagy modulators. Acute oxidative stress led to a marked increase in autophagy in the RPE, whereas autophagy was reduced under chronic oxidative stress. Upregulation of autophagy by rapamycin decreased oxidative stress-induced generation of reactive oxygen species (ROS), whereas inhibition of autophagy by 3-methyladenine (3-MA) or by knockdown of ATG7 or BECN1 increased ROS generation, exacerbated oxidative stress-induced reduction of mitochondrial activity, reduced cell viability, and increased lipofuscin. Examination of control human donor specimens and mice demonstrated an age-related increase in autophagosome numbers and expression of autophagy proteins. However, autophagy proteins, autophagosomes, and autophagy flux were significantly reduced in tissue from human donor AMD eyes and 2 animal models of AMD. In conclusion, our data confirm that autophagy plays an important role in protection of the RPE against oxidative stress and lipofuscin accumulation and that impairment of autophagy is likely to exacerbate oxidative stress and contribute to the pathogenesis of AMD.

  18. Research status of conbercept treating age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hai-Yan He

    2015-08-01

    Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

  19. The Association between Plasma 25-Hydroxyvitamin D and Subgroups in Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads Krüger; Subhi, Yousif

    2013-01-01

    To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis.......To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis....

  20. Age-Related Macular Degeneration: Clinical Findings following Treatment with Antiangiogenic Drugs

    Directory of Open Access Journals (Sweden)

    Ricardo Casaroli-Marano

    2014-01-01

    Full Text Available Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD in Spain. Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA, type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug. Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of 4.5±1.8 and 1.6±2.1 injections of antiangiogenic drugs, and 5.4±2.8 and 3.6±2.2 follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without. Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits, and a close monitoring might be the key to successfully manage nvAMD.

  1. A New System for Measuring Auto-Fluorescence Changes in Neovascular-AMD after Intravitreal Injection of Bavecizumab

    Directory of Open Access Journals (Sweden)

    Mohammad Norouzifard

    2011-07-01

    Full Text Available Age-Related Macular Degeneration (AMD is the second disease diabetes which causes blindness in aged people. The only remedy for AMD is intravenous injection of bavecizumab. To prove the efficiency of remedy, the degenerated cells in Macula should be measured. In this article, a modern system is introduced to measure Auto-Fluorescence in Macula part of retina in order to obtain number of degenerated cells. The system consists of three main parts: Pre-processing stage is omission of margins and reversion of images in retina. Analysis stage is in charge of classification of images and elicitation of their features. In classification the target areas are identified by methods like morphology, dynamic threshold and connected comportments and the features of target area including Euclidean distance to the center of image and density. In the stage of understanding by gathering the features of each class, we will get the measurable parameter of evaluating Auto Fluorescence by the help of which we can count the number of degenerated cells of Macula area. The results are coming from statistical analysis, including linear regression and correlation of data. Experiments have been done on a database of 34 retina images of AMD patients. The average statistical error rate is equal to76 percent. In clinical reviews, the founded relation to disinflation of Macula has been proved, while there were no proved relations to the vision decreasing or increasing of patients.

  2. The Incidence of Adjacent Segment Degeneration after Cervical Disc Arthroplasty (CDA): A Meta Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Yang, Baohui; Li, Haopeng; Zhang, Ting; He, Xijing; Xu, Siyue

    2012-01-01

    Background Cervical disc arthroplasty is being used as an alternative degenerative disc disease treatment with fusion of the cervical spine in order to preserve motion. However, whether replacement arthoplasty in the spine achieves its primary patient centered objective of lowering the frequency of adjacent segment degeneration is not verified yet. Methodology We conducted a meta-analysis according to the guidelines of the Cochrane Collaboration using databases including PubMed, Cochrane Central Register of Controlled Trials and Embase. The inclusion criteria were: 1) Randomized, controlled study of degenerative disc disease of the cervical spine involving single segment or double segments using Cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) as controls; 2) A minimum of two-year follow-up using imaging and clinical analyses; 3) Definite diagnostic evidences for “adjacent segment degeneration” and “adjacent segment disease”; 4) At least a minimum of 30 patients per population. Two authors independently selected trials; assessed methodological quality, extracted data and the results were pooled. Results No study has specifically compared the results of adjacent segment degenerative; Two papers describing 140 patients with 162 symptomatic cervical segment disorders and compared the rate of postoperative adjacent segment disease development between CDA and ACDF treatments, three publications describing the rate of adjacent-segment surgery including 1273 patients with symptomatic cervical segments. The result of the meta-analysis indicates that there were fewer the rate of adjacent segment disease and the rate for adjacent-segment surgery comparing CDA with ACDF, but the difference was not statistically significant. Conclusions Based on available evidence, it cannot be concluded, that CDA can significantly reduce the postoperative rate of the adjacent segment degenerative and adjacent segment disease. However, due to some

  3. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R; Lawrenson, John G

    2017-07-30

    There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C, and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). To determine whether or not taking antioxidant vitamin or mineral supplements, or both, prevent the development of AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29 March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 29 March 2017. We did not use any date or language restrictions in the electronic searches for trials. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in combination) to control. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We pooled data using a fixed-effect model. We graded the certainty of the evidence using GRADE. We included a total of five RCTs in this review with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias.Four studies reported the comparison of vitamin E with placebo. Average treatment and follow-up duration ranged from 4 to 10 years. Data were

  4. Bevasiranib for the Treatment of Wet, Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Adinoyi O. Garba

    2010-01-01

    Full Text Available Age- related Macular Degeneration (AMD is the leading cause of severe visual impairment in people 65 years and older in industrialized nations. Exudative, or “wet”, AMD is a late form of AMD (as distinguished from atrophic, so-called dry, AMD and is responsible for over 60% of all cases of blindness due to AMD. It is widely accepted that vascular endothelial growth factor (VEGF is a key component in the pathogenesis of choroidal neo-vascularization (CNV, which is a precursor to wet AMD. The current gold-standard for treating wet AMD is the monoclonal antibody fragment ranibizumab (trade name Lucentis, which targets VEGF. Other agents used to treat wet AMD include pegaptanib (Macugen, bevacizumab (Avastin; off-label use, and several other experimental agents. The advent of small interfering RNA (siRNA has presented a whole new approach to inhibiting VEGF. This article reviews the status of a novel siRNA-based therapeutic, bevasiranib, for the treatment of wet AMD. Bevasiranib is believed to work by down regulating VEGF production in the retina. Studies in human cell-lines and animal models have shown that VEGF siRNAs are effective in inhibiting VEGF production. Although there is a lack of sufficient published data on human studies supporting the use of bevasiranib for wet AMD, available data indicates that due to its unique mechanism of action, bevasiranib might hold some promise as a primary or adjunct treatment for wet AMD.

  5. [Risk factors for age-related macular degeneration].

    Science.gov (United States)

    Starzycka, M; Słomska, J; Górniak-Bednarz, A; Ortyl, E

    1997-01-01

    To present the results of examinations of the risk factors for age-related macular degeneration (AMD) carried out in the last 3 years. Our clinical material comprised 119 patients, 69 women and 50 men, aged 43-85, mean age 70 years. Using classification according to the worse eye, there were 20 patients with drusen, 27 with atrophic changes and 72 with exudative form and AMD. The following risk factors were evaluated: age, sex, body mass index, history of general medical conditions, cigarette smoking, sun exposure, family history of AMD and ocular conditions such as iris color, lens opacities, hyperopia, gerontoxon and changes in retinal vessels. The significant relationships were found between the development of AMD and the age of patients, as well as between the advanced forms of AMD and the history of cardiovascular diseases and sclerotic changes in retinal vessels, 87% of examined patients have light iris and 52% body mass index above 26. The studies confirmed the role of age in the development of AMD and indicated cardiovascular disturbances, increased body mass index and light iris as the possible risk factors for AMD that are most worth further studying. The special attention should be also paid to drusen as the risk factor of AMD.

  6. Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

    Science.gov (United States)

    Yonekawa, Yoshihiro; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

  7. The Arm Movement Detection (AMD) test: a fast robotic test of proprioceptive acuity in the arm.

    Science.gov (United States)

    Mrotek, Leigh Ann; Bengtson, Maria; Stoeckmann, Tina; Botzer, Lior; Ghez, Claude P; McGuire, John; Scheidt, Robert A

    2017-06-28

    We examined the validity and reliability of a short robotic test of upper limb proprioception, the Arm Movement Detection (AMD) test, which yields a ratio-scaled, objective outcome measure to be used for evaluating the impact of sensory deficits on impairments of motor control, motor adaptation and functional recovery in stroke survivors. Subjects grasped the handle of a horizontal planar robot, with their arm and the robot hidden from view. The robot applied graded force perturbations, which produced small displacements of the handle. The AMD test required subjects to respond verbally to queries regarding whether or not they detected arm motions. Each participant completed ten, 60s trials; in five of the trials, force perturbations were increased in small increments until the participant detected motion while in the others, perturbations were decreased until the participant could no longer detect motion. The mean and standard deviation of the 10 movement detection thresholds were used to compute a Proprioceptive Acuity Score (PAS). Based on the sensitivity and consistency of the estimated thresholds, the PAS quantifies the likelihood that proprioception is intact. Lower PAS scores correspond to higher proprioceptive acuity. Thirty-nine participants completed the AMD test, consisting of 25 neurologically intact control participants (NIC), seven survivors of stroke with intact proprioception in the more affected limb (HSS+P), and seven survivors of stroke with impaired or absent proprioception in the more affected limb (HSS-P). Significant group differences were found, with the NIC and HSS+P groups having lower (i.e., better) PAS scores than the HSS-P group. A subset of the participants completed the AMD test multiple times and the AMD test was found to be reliable across repetitions. The AMD test required less than 15 min to complete and provided an objective, ratio-scaled measure of proprioceptive acuity in the upper limb. In the future, this test could be

  8. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Keane PA

    2015-02-01

    Full Text Available Pearse A Keane,1 Gabriella de Salvo,2 Dawn A Sim,1 Srini Goverdhan,2 Rupesh Agrawal,1 Adnan Tufail1 1NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, 2Department of Ophthalmology, University Hospital Southampton NHS Foundation Trust, Southampton, UK Abstract: Treatment of the neovascular form of age-related macular degeneration (AMD has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. Keywords: Amsler, detection, choroidal neovascularization, hyperacuity, optical coherence tomography

  9. Progress of stem/progenitor cell-based therapy for retinal degeneration.

    Science.gov (United States)

    Tang, Zhimin; Zhang, Yi; Wang, Yuyao; Zhang, Dandan; Shen, Bingqiao; Luo, Min; Gu, Ping

    2017-05-10

    Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

  10. Progress on retinal image analysis for age related macular degeneration.

    Science.gov (United States)

    Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which

  11. Physical activity patterns in patients with early and late age-related macular degeneration

    DEFF Research Database (Denmark)

    Subhi, Yousif; Sørensen, Torben Lykke

    2016-01-01

    INTRODUCTION: Age-related macular degeneration (AMD) leads to visual impairment that affects visual functioning and thereby the ability to be physically active. We investigated physical activity patterns in patients with AMD. METHODS: Patients with early and late AMD and elderly controls were...... spent on walking outdoors. RESULTS: We recruited 198 participants of whom 196 were eligible for inclusion in the analyses (68 controls, 25 with early AMD and 103 with late AMD). The frequency of regular physical activity did not differ between patients with early and late AMD and elderly controls. Lower...... recruited for this hospital-based cross-sectional study. All participants had their best-corrected visual acuity measured and were interviewed about their physical activity based on questions that covered regular physical activity, physical activity that would work up sweat, climbing the stairs and time...

  12. The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment

    NARCIS (Netherlands)

    Geerlings, M.J.; Jong, E.K.; Hollander, A.I. den

    2017-01-01

    Age-related macular degeneration (AMD) is a progressive retinal disease and the major cause of irreversible vision loss in the elderly. Numerous studies have found both common and rare genetic variants in the complement pathway to play a role in the pathogenesis of AMD. In this review we provide an

  13. Autologous Translocation of the Retinal Pigment Epithelium and Choroid in the Treatment of Exudative Age-related Macular Degeneration

    NARCIS (Netherlands)

    K.J.M. Maaijwee (Kristel Johanna Maria)

    2008-01-01

    textabstractAge-related macular degeneration (AMD) is the most important cause of irreversible legal blindness in elderly persons in industrialized countries. AMD has two forms: atrophic (dry) and exudative (wet). In the wet form, abnormal blood vessels, arising from the choriocapillaris (choroidal

  14. Memory Loss, Dementia, and Stroke: Implications for Rehabilitation of Older Adults with Age-Related Macular Degeneration

    Science.gov (United States)

    Warren, Mary

    2008-01-01

    Older adults with age-related macular degeneration (AMD) are not immune to the other diseases of aging. Although AMD is the leading cause of low vision in older Americans, stroke is the leading cause of disability, and dementias affect another 2.5 million older Americans. Each condition alone can significantly impair a person's ability to…

  15. Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major ris...

  16. Olive Oil Consumption and Age-Related Macular Degeneration: The Alienor Study

    Science.gov (United States)

    Cougnard-Grégoire, Audrey; Merle, Bénédicte M. J.; Korobelnik, Jean-François; Rougier, Marie-Bénédicte; Delyfer, Marie-Noëlle; Le Goff, Mélanie; Samieri, Cécilia; Dartigues, Jean-François; Delcourt, Cécile

    2016-01-01

    Background Olive oil provides a mixture of lipids and antioxidant nutrients which may help preventing age-related diseases such as age-related macular degeneration (AMD). However, little is known about the associations between olive oil consumption and the risk of AMD. Objective To examine associations between olive oil use and AMD prevalence in elderly subjects. Methods Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) is a population-based study on eye diseases performed in elderly residents of Bordeaux (France). In 1999–2000, frequencies of consumption of main categories of dietary fats used were collected. In 2006–2088, AMD was graded from non mydriatic retinal photographs into three exclusive stages: no AMD, early AMD, and late AMD. Two categories of preferred dietary fat used (olive oil, n-3 rich oils, n-6 rich oils, mixed oils, butter and margarine) were defined: “no use” and “regular use” (using fat for spreading and/or cooking and/or dressing). Associations of AMD with each fat use were estimated using Generalized Estimating Equation logistic regressions models. Results Our study included 654 subjects (1269 eyes) with complete data (n = 268 eyes with early AMD and n = 56 with late AMD). After adjustment for potential confounders, regular use of olive oil was significantly associated with a decreased risk of late AMD (odds ratio [OR] = 0.44, 95% confidence interval [CI]: 0.21;0.91). In contrast, regular use of olive oil was not significantly associated with early AMD (OR = 0.84, 95%CI: 0.59;1.21). No associations were found between regular consumption of n-3 rich oils, n-6 rich oils, mixed oils, butter and margarine and AMD, whatever the stage. Conclusions This study suggests a protective effect of olive oil consumption for late AMD in this elderly community-dwelling population. Characterization of the mediating nutrients deserves further research. PMID:27467382

  17. Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

    NARCIS (Netherlands)

    Schmidt-Erfurth, Ursula; Eldem, Bora; Guymer, Robyn; Korobelnik, Jean-Franc̦ois; Schlingemann, Reinier O.; Axer-Siegel, Ruth; Wiedemann, Peter; Simader, Christian; Gekkieva, Margarita; Weichselberger, Andreas

    2011-01-01

    Objective: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: A 12-month, multicenter, randomized, double-masked,

  18. Striatonigral Degeneration

    Science.gov (United States)

    ... See More About Research The NINDS supports and conducts research on disorders of the brain and nervous system such as striatonigral degeneration. This research ... Publications Definition Striatonigral ...

  19. Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Akshay Anand

    2013-01-01

    Full Text Available Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1 in patients of age-related macular degeneration (AMD and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (χ2=10.516, df=8, P=0.231 indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P=.0001 with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

  20. Prospective Study of Plasma Homocysteine Level and Risk of Age-related Macular Degeneration in Women

    Science.gov (United States)

    Christen, William G.; Cook, Nancy R.; Ridker, Paul M.; Buring, Julie E.

    2014-01-01

    Purpose Prospective data to examine the association of homocysteine and age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. Methods We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results During an average of 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually-significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.95–1.63; p for trend, 0.07) and visually-significant AMD (HR, 1.41; 95% CI, 0.92–2.17; p for trend, 0.052) in age- and treatment-adjusted analyses. Conclusions These prospective data from a large cohort of apparently-healthy women do not support a strong role for homocysteine in AMD occurrence. PMID:25777307

  1. A 4-Year Longitudinal Study of 555 Patients Treated with Ranibizumab for Neovascular Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara B; Fuchs, Josefine

    2013-01-01

    To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years.......To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years....

  2. Vision Rehabilitation is Part of AMD Care

    Directory of Open Access Journals (Sweden)

    August Colenbrander

    2018-01-01

    Full Text Available AMD does not just affect the retina. It severely affects people’s lives. Paying attention to this aspect will only become more important as the population ages and more otherwise healthy individuals become affected. This paper will discuss the need for teamwork to overcome the difference between medical care, which addresses the causes of AMD, and rehabilitative care, which addresses the consequences. Different aspects and different degrees of vision loss ask for different interventions. Loss of detailed vision can be addressed by a wide variety of magnification devices. The means to address this aspect are well recognized. Surround vision is largely processed pre-attentively. Its loss cannot be remediated by devices, but must be addressed through patient education to bring previously subconscious reactions to conscious awareness. Loss of contrast vision is an aspect that is not sufficiently studied. It is important for early detection, and for the safety of the patient. When the eye condition cannot be modified, environmental modifications provide the most effective remediation.

  3. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

  4. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  5. Current surgical treatment of age-related macular degeneration

    NARCIS (Netherlands)

    Ramos de Carvalho, J. Emanuel; Willig, A. J. H. E.; Chung, R.; Peiretti, E.; Mura, M.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe, irreversible central vision loss in individuals over 65 years of age throughout much of the developed world. The advent of anti-VEGF therapy has had a great impact in the long-term natural history of this condition, more

  6. Age-related macular degeneration in Onitsha, Nigeria | Nwosu ...

    African Journals Online (AJOL)

    Objectives: To determine the incidence, pattern and ocular morbidity associated with age-related macular degeneration (AMD) at the Guinness Eye Center Onitsha Nigeria. Materials and Methods: The case files of all new patients aged 50 years and above seen between January 1997 and December 2004 were reviewed.

  7. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...

  8. Genetic association study of Age-Related Macular Degeneration in the Spanish population

    Science.gov (United States)

    Brión, María; Sanchez-Salorio, Manuel; Cortón, Marta; de la Fuente, Maria; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Goncalo; Sobrino, Beatriz; Carracedo, Angel

    2017-01-01

    Purpose To investigate new genetic risk factors and replicate reported associations with advanced age related macular degeneration (AMD) in a prospective case - control study developed with a Spanish cohort. Methods Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex™ genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3´UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. PMID:21106043

  9. Reading speed does not benefit from increased line spacing in AMD patients.

    Science.gov (United States)

    Chung, Susana T L; Jarvis, Samuel H; Woo, Stanley Y; Hanson, Kara; Jose, Randall T

    2008-09-01

    Crowding, the adverse spatial interaction due to the proximity of adjacent targets, has been suggested as an explanation for slow reading in peripheral vision. Previously, we showed that increased line spacing, which presumably reduces crowding between adjacent lines of text, improved reading speed in the normal periphery (Chung, Optom Vis Sci 2004;81:525-35). The purpose of this study was to examine whether or not individuals with age-related macular degeneration (AMD) would benefit from increased line spacing for reading. Experiment 1: Eight subjects with AMD read aloud 100-word passages rendered at five line spacings: the standard single spacing, 1.5x, 2x, 3x, and 4x the standard spacing. Print sizes were 1x and 2x of the critical print size. Reading time and number of reading errors for each passage were measured to compute the reading speed. Experiment 2: Four subjects with AMD read aloud sequences of six 4-letter words, presented on a computer monitor using the rapid serial visual presentation (RSVP) paradigm. Target words were presented singly, or flanked above and below by two other words that changed in synchrony with the target word, at various vertical word separations. Print size was 2x the critical print size. Reading speed was calculated based on the RSVP exposure duration that yielded 80% of the words read correctly. Averaged across subjects, reading speeds for passages were virtually constant for the range of line spacings tested. For sequences of unrelated words, reading speeds were also virtually constant for the range of vertical word separations tested, except at the smallest (standard) separation at which reading speed was lower. Contrary to the previous finding that reading speed improved in normal peripheral vision, increased line spacing in passages, or increased vertical separation between words in RSVP, did not lead to improved reading speed in people with AMD.

  10. Pathogenesis and prophylaxis of AMD: focus on oxidative stress and antioxidants

    Directory of Open Access Journals (Sweden)

    Anna Wiktorowska-Owczarek

    2010-07-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe visual loss and blindness in people over 55. Its pathogenesis – likely multifactorial, involving a complex interaction of metabolic, functional, genetic and environmental factors – remains poorly understood. Among molecular links in pathogenesis of AMD is the oxidative stress in the retina, a structure that is particularly susceptible to damage by reactive oxygen species (ROS since photoreceptor outer segment (POS membranes are rich in polyunsaturated fatty acids which can be readily oxidized and can initiate a cytotoxic chain reaction. Occurring in the neighborhood of photoreceptors, the retinal pigment epithelial cells (RPE actively contribute to both the retinoid cycle and catabolism of constantly shed and phagocytized parts of photoreceptor outer segments. Enzymatic degradation of photoreceptor fragments occurring in RPE phagolysosomes is not complete and undigested material in the form of insoluble aggregates, called lipofuscin, is deposited in lysosomes of RPE cells. Lipofuscin contains a mixture of diverse molecular components including retinoid-derived compounds, some of which displaying potent photoinducible properties, contributing to an enhancement and propagation of the oxidative stress. The retina possesses defense mechanisms against the oxidative stress that effectively neutralize the consequences of reactive oxygen species actions under normal conditions. A key role in the antioxidant defense plays an array of substances, including: xanthophylls (lutein and zeaxanthin, vitamin C and E, and glutathione. This paper surveys the current concepts on the role of the oxidative stress in pathophysiology of AMD, and describes major components of the antioxidant defense system, including their use in AMD prophylaxis and therapy.

  11. Pigment epithelial detachment followed by retinal cystoid degeneration leads to vision loss in treatment of neovascular age-related macular degeneration.

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M; Deak, Gabor-Gyoergy; Kundi, Michael; Simader, Christian

    2015-04-01

    Intravitreal antiangiogenic therapy is the major therapeutic breakthrough in neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) is the leading diagnostic tool, but solid criteria for optimal therapeutic outcomes are lacking. A comprehensive analysis of structure/function correlations using Food and Drug Administration- and European Medicines Agency-approved substances and fixed and flexible regimens was performed. Post hoc analysis of a prospective, randomized multicenter clinical trial including 189 study sites. A total of 1240 patients with active neovascular AMD. Participants received intravitreal ranibizumab or aflibercept. A fixed regimen was used for 48 weeks followed by a flexible regimen until week 96. At monthly intervals, best-corrected visual acuity (BCVA) was measured and retinal morphology was assessed by standardized OCT, including intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachment (PED), presenting with a width ≥400 μm or a height of ≥200 μm. Results were correlated for each regimen, feature, and time. The BCVA outcomes in relation to retinal pathomorphology based on noninferiority for all treatment arms. In neovascular AMD, only IRC at baseline and persistent through week 12 had a negative impact on BCVA. With therapeutic intervention, exudative features such as IRC and SRF resolved rapidly in 74% of eyes, whereas PED responded only slowly with 38%. Independent of the type of regimen, fixed or flexible, retinal morphology correlated tightly with visual function. Intraretinal cysts consistently showed the lowest BCVA gains with either regimen or substance. With the switch from a fixed to a flexible pro re nata (PRN) regimen, progressive visual loss occurred exclusively in the group with primary PED presenting as the hallmark of neovascular activity and was induced by secondary formation of IRC in the neurosensory retina. The efficacy of antiangiogenic therapy in neovascular

  12. Hepatocerebral degeneration

    Science.gov (United States)

    Hepatocerebral degeneration is a brain disorder that occurs in people with liver damage. ... This condition may occur in any case of acquired liver failure, ... can damage brain tissue. Specific areas of the brain, such as ...

  13. Oxidative stress, innate immunity, and age-related macular degeneration

    Science.gov (United States)

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  14. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Szaflik, Jacek P.; Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika; Zaras, Magdalena; Wozniak, Katarzyna; Szaflik, Jerzy; Blasiak, Janusz

    2009-01-01

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  15. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  16. Static and flicker perimetry in age-related macular degeneration.

    Science.gov (United States)

    Luu, Chi D; Dimitrov, Peter N; Wu, Zhichao; Ayton, Lauren N; Makeyeva, Galina; Aung, Khin-Zaw; Varsamidis, Mary; Robman, Luba; Vingrys, Algis J; Guymer, Robyn H

    2013-05-01

    The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. The pattern of change in sensitivity and percentage of abnormal eyes for static perimetry across all AMD severity groups were similar to flicker perimetry. Eyes with drusen > 125 μm (P[static] = 0.018, P[flicker] = 0.024), drusenoid epithelial detachment (P[static and flicker] flicker] flicker sensitivities compared to normal eyes. Static (β-coefficient -1.59, 95% confidence interval [CI] -4.78-1.60) and flicker (β-coefficient -1.29, 95% CI -4.66-2.08) sensitivities declined at a similar rate in eyes that showed clinical signs of progression. Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 μm are present, but before the development of late AMD.

  17. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  18. A seeded ambient temperature ferrite process for treatment of AMD ...

    African Journals Online (AJOL)

    A seeded ambient temperature ferrite process for treatment of AMD waters: magnetite formation in the presence and absence of calcium ions under steady state operation. ... promising for AMD treatment. Keywords: Ferrite process, Magnetite seed, Calcium interference, Acid mine drainage (WaterSA: 2003 29(2): 117-124) ...

  19. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

    Directory of Open Access Journals (Sweden)

    Liu Melissa M

    2012-08-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

  20. Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

    Science.gov (United States)

    Pinazo-Durán, Maria D.; Gómez-Ulla, Francisco; Arias, Luis; Araiz, Javier; Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; García-Medina, Jose J.; López-Gálvez, Maria Isabel; Manzanas, Lucía; Salas, Anna; Zapata, Miguel; Diaz-Llopis, Manuel; García-Layana, Alfredo

    2014-01-01

    Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids (ω-3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD. PMID:24672708

  1. Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease.

    Science.gov (United States)

    Gorin, Michael B; Weeks, Daniel E; Baron, Robert V; Conley, Yvette P; Ortube, Maria C; Nusinowitz, Steven

    2014-11-28

    The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

  2. Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease

    Directory of Open Access Journals (Sweden)

    Michael B. Gorin

    2014-11-01

    Full Text Available The key to reducing the individual and societal burden of age-related macular degeneration (AMD-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

  3. Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

    Directory of Open Access Journals (Sweden)

    Maria D. Pinazo-Durán

    2014-01-01

    Full Text Available Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD, as well as the role of antioxidants (AOX and omega-3 fatty acids (ω-3 supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain. Results. High dietary intakes of ω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

  4. Combination of ranibizumab with photodynamic therapy vs ranibizumab monotherapy in the treatment of age-related macular degeneration:a systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Jun-Kang Si

    2014-06-01

    Full Text Available AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy (PDT vs ranibizumab monotherapy in the treatment of age-related macular degeneration (AMD.METHODS:The Cochrane Central Register of Controlled Trials (CENTRAL in the Cochrane Library, Pubmed, and Embase were searched. There were no language or data restrictions in the search for trials. Only randomized controlled trials (RCTs were included. Methodological quality of the literatures was evaluated according to the Jadad Score. RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review, among which four of them were included in quantitative analysis. The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity (BCVA change vs baseline at month 12 compared with that of the combination treatment group, and the statistical difference was significant (WMD, -2.61; 95% CI, -5.08 to -0.13; P=0.04. However, after the removal of one study, the difference between the two groups showed no significant difference (WMD, -2.29; 95% CI, -4.81 to 0.23; P=0.07. Meanwhile, no significant central retinal thickness (CRT reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up. Nevertheless, the combination group tended to have a greater reduction in CRT (WMD, -4.13μm; 95%CI, -25.88 to 17.63, P=0.71. The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference (RR, 0.72; 95% CI, 0.54 to 0.95; P=0.02. Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month 12 between the two groups (RR, 0.93; 95% CI, 0.76 to 1.15; P=0.52. The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab

  5. The complex model of risk and progression of AMD estimation

    Directory of Open Access Journals (Sweden)

    V. S. Akopyan

    2012-01-01

    Full Text Available Purpose: to develop a method and a statistical model to estimate individual risk of AMD and the risk for progression to advanced AMD using clinical and genetic risk factors.Methods: A statistical risk assessment model was developed using stepwise binary logistic regression analysis. to estimate the population differences in the prevalence of allelic variants of genes and for the development of models adapted to the population of Moscow region genotyping and assessment of the influence of other risk factors was performed in two groups: patients with differ- ent stages of AMD (n = 74, and control group (n = 116. Genetic risk factors included in the study: polymorphisms in the complement system genes (C3 and CFH, genes at 10q26 locus (ARMS2 and HtRA1, polymorphism in the mitochondrial gene Mt-ND2. Clinical risk factors included in the study: age, gender, high body mass index, smoking history.Results: A comprehensive analysis of genetic and clinical risk factors for AMD in the study group was performed. Compiled statis- tical model assessment of individual risk of AMD, the sensitivity of the model — 66.7%, specificity — 78.5%, AUC = 0.76. Risk factors of late AMD, compiled a statistical model describing the probability of late AMD, the sensitivity of the model — 66.7%, specificity — 78.3%, AUC = 0.73. the developed system allows determining the most likely version of the current late AMD: dry or wet.Conclusion: the developed test system and the mathematical algorhythm for determining the risk of AMD, risk of progression to advanced AMD have fair diagnostic informative and promising for use in clinical practice.

  6. Classification of wet aged related macular degeneration using optical coherence tomographic images

    Science.gov (United States)

    Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

    2013-12-01

    Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

  7. The Societal Impact of Age-Related Macular Degeneration: Use of Social Support Resources Differs by the Severity of the Impairment

    Science.gov (United States)

    Brennan, Mark; Horowitz, Amy; Reinhardt, Joann P.; Stuen, Cynthia; Rubio, Roman; Oestreicher, Nina

    2011-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among persons aged 50 years and older and is most prevalent among individuals of European descent aged 65 and older (Friedman et al., 2004; Rosenthal & Thompson, 2003). By affecting central vision, AMD interferes with such tasks as reading, driving, and activities…

  8. Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

    DEFF Research Database (Denmark)

    Singh, Amardeep; Subhi, Yousif; Nielsen, Marie Krogh

    2017-01-01

    Age-related macular degeneration (AMD) is a degenerative disease of the retina and a leading cause of irreversible vision loss. We investigated the systemic differences in the frequency of T helper (Th) 1 and Th17 cells in patients with non-exudative and exudative AMD and compared to age...

  9. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA)

    Science.gov (United States)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat; Larsen, Michael; Souied, Eric; Schlingemann, Reinier; Eldem, Bora; Monés, Jordi; Richard, Gisbert; Bandello, Francesco

    2014-01-01

    Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. Trial registration number NCT01318941. PMID:25136079

  10. The Incidence of Adjacent Segment Degeneration after Cervical Disc Arthroplasty (CDA): A Meta Analysis of Randomized Controlled Trials

    OpenAIRE

    Yang, Baohui; Li, Haopeng; Zhang, Ting; He, Xijing; Xu, Siyue

    2012-01-01

    BACKGROUND: Cervical disc arthroplasty is being used as an alternative degenerative disc disease treatment with fusion of the cervical spine in order to preserve motion. However, whether replacement arthoplasty in the spine achieves its primary patient centered objective of lowering the frequency of adjacent segment degeneration is not verified yet. METHODOLOGY: We conducted a meta-analysis according to the guidelines of the Cochrane Collaboration using databases including PubMed, Cochrane Ce...

  11. Total disc arthroplasty does not affect the incidence of adjacent segment degeneration in cervical spine: results of 93 patients in three prospective randomized clinical trials.

    Science.gov (United States)

    Jawahar, Ajay; Cavanaugh, David A; Kerr, Eubulus J; Birdsong, Elisa M; Nunley, Pierce D

    2010-12-01

    Advancements in the philosophy of "motion preservation" have led to the use of total disc arthroplasty (TDA) as an alternative to fusion for degenerative disc disease (DDD) in the cervical spine. A commonly proposed theory is that TDA could reduce the incidence of adjacent segment disease. All the published clinical studies for TDA discuss the "equal efficacy" results of different investigational device exemption (IDE) trials between TDA and anterior cervical discectomy and fusion (ACDF) but have not addressed the issue of adjacent segment disease. To present the comparison of outcome data with respect to clinical success rates, symptom-free period, and incidence of adjacent segment disease in 93 patients with one- and two-level cervical DDD treated with TDA or ACDF in three different Food and Drug Administration (FDA) investigational trials. Prospective, randomized, FDA IDE trials. Ninety-three patients with established symptomatic one-or two-level cervical disc disease who failed to respond to conservative treatment were randomized to receive TDA (59) or ACDF (34) as part of clinical trials involving three different artificial discs at our institution. Subjects were blind to the assigned group until after the surgery. Visual analog pain score (VAS), Neck Disability Index, and cervical spine radiographs were collected at 6 weeks and at 3, 6, 12, 24, 36, and 48 months after surgery. Success of the index surgery was assessed based on outcome measures at the seven data points. Success was defined as reduction by more than 30 points in both VAS and Neck Disability Index, absence of neurological deficits, and no further intervention at the index level. Adjacent segment disease was established by radiology, neurophysiology, and subsequent interventions administered to the patients. At median follow-up of 37 months (range, 24-49 months), 64 (25 ACDF and 39 TDA) patients satisfied the criteria for clinical success. Neck Disability Index was a better predictor of outcome

  12. Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

    Science.gov (United States)

    DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

  13. Hypomethylation of IL17RC Promoter Associates with Age-related Macular Degeneration

    Science.gov (United States)

    Wei, Lai; Liu, Baoying; Tuo, Jingsheng; Shen, Defen; Chen, Ping; Li, Zhiyu; Liu, Xunxian; Ni, Jia; Dagur, Pradeep; Sen, H. Nida; Jawad, Shayma; Ling, Diamond; Park, Stanley; Chakrabarty, Sagarika; Meyerle, Catherine; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.; McCoy, J. Philip; Blum, Emily; Francis, Peter J.; Klein, Michael L.; Guymer, Robyn H.; Baird, Paul N.; Chan, Chi-Chao; Nussenblatt, Robert B.

    2012-01-01

    SUMMARY Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its etiology. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. PMID:23177625

  14. Prevalence of Age-Related Macular Degeneration in Australia: The Australian National Eye Health Survey.

    Science.gov (United States)

    Keel, Stuart; Xie, Jing; Foreman, Joshua; van Wijngaarden, Peter; Taylor, Hugh R; Dirani, Mohamed

    2017-11-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among the elderly population globally. Currently, knowledge of the epidemiology of AMD in Australia remains scarce because of a paucity of recent population-based data. To examine the prevalence of AMD in Australia. In this population-based, cross-sectional survey performed from March 11, 2015, to April 18, 2016, a sample of 3098 nonindigenous Australians 50 years and older and 1738 indigenous Australians 40 years and older from 30 geographic areas across Australia were examined. Any AMD, early AMD, intermediate AMD, and late AMD graded according to the Beckman clinical classification system. A total of 4836 individuals were examined, including 3098 nonindigenous Australian (64.1%; 58.9% female vs 41.1% male; age range, 40-92 years; mean [SD] age, 55.0 [10.0] years) and 1738 indigenous Australians (35.9%; 53.6% female vs 46.4% male; age range, 50-98 years; mean [SD] age, 66.6 [9.7] years). A total of 4589 (94.9%, 2946 nonindigenous and 1643 indigenous) participants had retinal photographs in at least 1 eye that were gradable for AMD. The weighted prevalence of early AMD was 14.8% (95% CI, 11.7%-18.6%) and of intermediate AMD was 10.5% (95% CI, 8.3%-13.1%) among nonindigenous Australians. In indigenous Australians, the weighted prevalence of early AMD was 13.8% (95% CI, 9.7%-19.3%) and of intermediate AMD was 5.7% (96% CI, 4.7%-7.0%). Late AMD was found in 0.96% (95% CI, 0.59%-1.55%) of nonindigenous participants (atrophic, 0.72%; neovascular, 0.24%). The prevalence of late AMD increased to 6.7% in participants 80 years or older and was higher in men (1.4% vs 0.61%, P = .02). Only 3 (0.17% [95% CI, 0.04%-0.63%]) indigenous participants had late (atrophic) AMD. Age-related macular degeneration was attributed as the main cause of vision loss (Australia.

  15. Patients' experiences of nursing actions during intravitreal treatment for wet age-related macular degeneration

    OpenAIRE

    Rönn Emsfors, Åsa; Elgán, Carina

    2015-01-01

    Purpose: The aim was to identify and describe nursing actions performed by nursing staff in which patients with wet age-related macular degeneration (AMD) experience good nursing care. Method: An explorative and descriptive qualitative design based on the Critical incident technique (CIT) was used. A strategic sample of 16 patients, aged 61-87 years (eleven women and five men) with wet AMD who received intravitreal treatment were interviewed. Results: Two main areas of good nursing care was i...

  16. Anker Energy battles AMD in West Virginia

    International Nuclear Information System (INIS)

    Frey, T.J.

    1998-01-01

    To comply with the Surface Mining Control and Reclamation Act of 1977, Anker Energy has a number of reclamation projects in progress in northern West Virginia to fight acid mine drainage (AMD), the number one reclamation problem in the region. Anker's reclamation activities range from water treatment systems to the backhaul and use of coal ash from its customers. The article describes the passive treatment system - successive alkalinity producing system (SAPS) used at the Ankar subsidiary Upshur Property Inc., in Upshur Country, W.Va., and a similar passive system used at the Green Run site in Albright, W.Va. A backhaul and ash utilization water treatment system is used by Anker subsidiary Patriot Mining Co. Inc., for water discharged from a surface mine into the Cheat River in Albright. In another ash project, the Stacks Run Refuse Reprocessing Project in Preston County, W.Va., refuse placed 10 years ago in abandoned pits is excavated, mixed with coal, burned with limestone and the CFB ash used in reclamation. At Patriot's Osaga surface mine ditches are filled with slag from old steel mills to generate alkalinity. At Pete Dye a golf course has been built on land mined by Consolidation Coal. 7 photos

  17. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  18. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  19. Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: implications for clinical trials in Alzheimer's disease.

    Science.gov (United States)

    Savory, J; Huang, Y; Wills, M R; Herman, M M

    1998-04-01

    A clinical trial in patients with Alzheimer's disease has indicated that frequent intramuscular (i.m.) treatment with desferrioxamine (DFO) slows progression of the disease. Confirmatory trials have not been carried out, partly because of the rigors of twice daily intramuscular injections over a period of 2 years, even though the initial report gave promising results. The aim of the present study was to determine an optimal DFO treatment protocol in an animal model exhibiting Alzheimer's-like intraneuronal protein aggregates, previously shown to be partially reversed by such treatment. New Zealand white rabbits were injected intracisternally with either aluminum (Al) maltolate or with saline on day 0. Intramuscular injections of DFO were given to selected rabbits for 2 days prior to sacrifice on days 4, 6 or 8. Bielschowsky's silver impregnation demonstrated widespread neurofibrillary degeneration (NFD) in neuronal cell bodies and neurites of brain and spinal cord from Al-treated rabbits. Monoclonal antibodies Tau-2, AT8, PHF-1 and Alz-50, all of which characteristically stain neurofibrillary tangles associated with Alzheimer's disease, strongly labeled the Al-induced NFD. The number of positive neurons and staining intensities were much less in rabbits treated with Al and subsequently with DFO, than in animals only given Al. Control rabbit receiving intracisternal saline were negative for NFD. The results of quantitative immunohistochemistry using image analysis confirmed that immunostaining densities with all tau mAbs were higher in Al-treated than in Al-DFO-treated or in saline-treated controls. Furthermore, it appears that hyperphosphorylation of tau does not make this protein resistant to degradation once Al has been removed by DFO treatment. The effectiveness of only two days of DFO treatment in reversing Al-induced neurofibrillary degeneration suggests that further clinical trials of DFO for treatment of Alzheimer's disease should be attempted using much

  20. Ranibizumab vs. aflibercept for wet age-related macular degeneration

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith

    2015-01-01

    the efficacy and safety of reduced frequency dosing for aflibercept, relative to other approved and marketed vascular endothelial growth factor inhibitors for wet AMD, over 12 months. RESEARCH DESIGN AND METHODS: Based on a systematic literature review performed according to a pre-specified protocol......OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  1. Systemic and Ocular Long Pentraxin 3 in Patients with Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Juel, Helene Bæk; Faber, Carsten; Fog, Lea Munthe

    2015-01-01

    Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One......CRP or CFH genotype. The gene expression of PTX3 increased in RPE/choroid with age (P=0.0098 macular; P=0.003 extramacular), but did not differ between aged controls and AMD patients. In vitro, ARPE-19 cells increased expression of the PTX3 gene as well PTX3 apical secretions after stimulation with TNF...

  2. Effect of lutein intervention on visual function in patients with early age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Chan Li

    2017-11-01

    Full Text Available AIM: To study the effect of lutein intervention on visual function of patients with early age-related macular degeneration(AMD. METHODS: Totally 200 early AMD patients were divided into lutein intervention group(20mg/dand placebo group by a randomized, double-blind, placebo-controlled trail. Questionnaire investigation, serum lutein concentration and visual function were conducted at baseline, 12, 24, 36 and 48wk respectively. RESULTS: The serum lutein concentration in lutein intervention group was higher than the baseline(PPPPP>0.05. CONCLUSION: Lutein intervention can improve the visual function of patients with early AMD.

  3. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland.......To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  4. A prospective study of treatment patterns and 1-year outcome of Asian age-related macular degeneration and polypoidal choroidal vasculopathy.

    Directory of Open Access Journals (Sweden)

    Chui Ming Gemmy Cheung

    Full Text Available OBJECTIVE: To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV and polypoidal choroidal vasculopathy (PCV. DESIGN: Prospective cohort, non-interventional study. METHODS: 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA and optical coherence tomography (OCT measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. MAIN OUTCOME MEASURE: Type of treatment, number of Anti-vascular endothelial growth factor (VEGF treatments, visual outcome over one year. RESULTS: Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021. Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month 12, mean VA improved from 0.82 (∼20/132 at baseline to 0.68 (∼20/96 at month 12 (mean gain 6.5 ETDRS letters, p = 0.002. 34.2% of eyes (38/113 eyes gained ≥15 ETDRS letters and 14.4% (16/113 eyes lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51. Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. CONCLUSIONS: There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality

  5. Small, hard macular drusen and peripheral drusen: associations with AMD genotypes in the Inter99 Eye Study

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Ek, Jakob; Kessel, Line

    2010-01-01

    PURPOSE: To study associations of small, hard macular drusen and peripheral drusen with genotypes associated with age-related macular degeneration (AMD). METHODS: Digital grayscale fundus photographs recorded in red-free illumination were graded for the presence of drusen in 1107 subjects aged 30...... to 66 years. Participants were genotyped for AMD-related polymorphisms in complement factor H (CFH), in LOC387715, and in complement factor B (CFB). RESULTS: The prevalence of 20 or more small, hard macular drusen per eye was 14%, with no association to the investigated polymorphisms. Peripheral drusen...... were associated with CFHY402H (odds ratio [OR], 4.3; 95% confidence interval [95% CI], 1.4-13, for CC versus TT genotypes) as was macular drusen >63 microm (OR, 1.9; 95% CI, 1.1-3.1, for CC versus TT genotypes). Macular drusen >63 microm were associated with the presence of 20 or more small, hard...

  6. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    Science.gov (United States)

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  7. The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self-Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.

    Science.gov (United States)

    Moran, Rachel; Beatty, Stephen; Stack, Jim; O'Halloran, Aisling M; Feeney, Joanne; Akuffo, Kwadwo O; Peto, Tunde; Kenny, Rose Anne; Nolan, John M

    2018-03-01

    To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD). Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50 years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD. Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 ± 0.132 µmol) and Group 4 (mean = 0.2040 ± 0.121 µmol/L) were significantly lower than Group 1 (mean = 0.4691 ± 0.0.372 µmol/L) and Group 3 (mean = 0.3176 ± 0.0.235 µmol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively. A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.

  8. Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial.

    Science.gov (United States)

    Rakoczy, Elizabeth P; Lai, Chooi-May; Magno, Aaron L; Wikstrom, Matthew E; French, Martyn A; Pierce, Cora M; Schwartz, Steven D; Blumenkranz, Mark S; Chalberg, Thomas W; Degli-Esposti, Mariapia A; Constable, Ian J

    2015-12-12

    Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection. In this single-centre, phase 1, randomised controlled trial, we enrolled patients with wet age-related macular degeneration at the Lions Eye Institute and the Sir Charles Gairdner Hospital (Nedlands, WA, Australia). Eligible patients had to be aged 65 years or older, have age-related macular degeneration secondary to active subfoveal choroidal neovascularisation, with best corrected visual acuity (BCVA) of 3/60-6/24 and 6/60 or better in the other eye. Patients were randomly assigned (3:1) to receive either 1 × 10(10) vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1 × 10(11) vg (high-dose rAAV.sFLT-1 group), or no gene-therapy treatment (control group). Randomisation was done by sequential group assignment. All patients and investigators were unmasked. Staff doing the assessments were masked to the study group at study visits. All patients received ranibizumab at baseline and week 4, and rescue treatment during follow-up based on prespecified criteria including BCVA measured on the Early Treatment Diabetic Retinopathy Study (EDTRS) scale, optical coherence tomography, and fluorescein angiography. The primary endpoint was ocular and systemic safety. This trial is registered with ClinicalTrials.gov, number NCT01494805. From Dec 16, 2011, to April 5, 2012, we enrolled nine patients of whom eight were randomly assigned to receive either intervention (three patients in the low-dose rAAV.sFLT-1 group and three patients in the high-dose rAAV.sFLT-1 group) or no treatment (two patients in the control group). Subretinal injection of r

  9. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    Science.gov (United States)

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  10. Different Strategies for the Treatment of Age-Related Macular Degeneration in China: An Economic Evaluation

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    Bin Wu

    2016-01-01

    Full Text Available Purpose. To assess the cost-effectiveness of bevacizumab compared to ranibizumab, verteporfin photodynamic therapy (PDT, and usual care for the treatment of age-related macular degeneration (AMD in China. Methods. A Markov model was developed according to patient visual acuity (VA in the better-seeing eye (Snellen scale. Four cohorts of patients were treated with one of the following therapies: bevacizumab, ranibizumab, PDT, or usual care. Clinical data related to treatments were obtained from published randomized clinical trials. Direct medical costs and resource utilization in the Chinese health care setting were taken into account. Health and economic outcomes were evaluated over a lifetime horizon. Sensitivity analyses were performed. Results. Treatment with ranibizumab provided the greatest gains in quality-adjusted life-years (QALYs. The cost per marginal QALY gained with bevacizumab over usual care was $1,258, $3,803, and $2,066 for the predominantly classic, minimally classic, and occult lesions, respectively. One-way sensitivity analysis showed considerably influential factors, such as utility values and effectiveness data. Probabilistic sensitivity analysis indicated that, compared to usual care, PDT and ranibizumab most cases would be cost-effective in the bevacizumab arm at a threshold of $7,480/QALY. Conclusion. Bevacizumab can be a cost-effective option for the treatment of AMD in the Chinese setting.

  11. Longitudinal Analysis of Drusen Volume in Intermediate Age-Related Macular Degeneration Using Two Spectral-Domain Optical Coherence Tomography Scan Patterns.

    Science.gov (United States)

    Thiele, Sarah; Nadal, Jennifer; Fleckenstein, Monika; Fang, Petra P; Pfau, Maximilian; Schmid, Matthias; Hua, Rui; Holz, Frank G; Schmitz-Valckenberg, Steffen

    2018-01-01

    To evaluate two different spectral-domain optical coherence tomography (SD-OCT) scan patterns in eyes with intermediate age-related macular degeneration (AMD) for the longitudinal assessment of drusen volume. The data of 38 eyes of 38 AMD patients (age 69.97 ± 6.08 years) were included. The longitudinal drusen volume over 4 years was analyzed by annual SD-OCT raster scanning (field size 20 × 15°). Two raster scan patterns (A/B) differed in the distance between neighboring B-scans (240 vs. 30 µm) and in the number of averaged frames (4 vs. 15). The mean drusen volume at baseline was 0.213 ± 0.100 mm3 (pattern A) and 0.219 ± 0.103 mm3 (pattern B) (p = 0.937). Linear mixed-effect models showed no significant difference for the change within 4 years for both pattern A (p = 0.8) and pattern B (p = 0.8). The results indicate that the performance of interpolation algorithms may be sufficient to balance for less dense raster scanning with regard to quantification of longitudinal drusen volume, which can be used as a surrogate marker for AMD progression in future clinical trials. © 2018 S. Karger AG, Basel.

  12. Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review

    Directory of Open Access Journals (Sweden)

    Sudhakar John

    2013-01-01

    Full Text Available Background. Age-related macular degeneration (AMD is a complex disorder that affects primarily the macula involving the retinal pigment epithelium (RPE but also to a certain extent the photoreceptor layer and the retinal neurons. Cell transplantation is a promising option for AMD and clinical trials are underway using different cell types. Methods. We hypothesize that instead of focusing on a particular cell source for concurrent regeneration of all the retinal layers and also to prevent exhaustive research on an array of cell sources for regeneration of each layer, the choice should depend on, precisely, which layer is damaged. Results. Thus, for a damage limited to the retinal pigment epithelial (RPE layer, the choice we suggest would be RPE cells. When the damage extends to rods and cones, the choice would be bone marrow stem cells and when retinal neurons are involved, relatively immature stem cell populations with an inherent capacity to yield neuronal lineage such as hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells can be tried. Conclusion. This short review will prove to be a valuable guideline for those working on cell therapy for AMD to plan their future directions of research and therapy for this condition.

  13. A Longitudinal Follow-Up Study of Saffron Supplementation in Early Age-Related Macular Degeneration: Sustained Benefits to Central Retinal Function

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    M. Piccardi

    2012-01-01

    Full Text Available Objectives. In a previous randomized clinical trial (Falsini et al. (2010, it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD. The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration. Design. Longitudinal, interventional open-label study. Setting. Outpatient ophthalmology setting. Participants. Twenty-nine early AMD patients (age range: 55–85 years with a baseline visual acuity >0.3. Intervention. Saffron oral supplementation (20 mg/day over an average period of treatment of 14 (±2 months. Measurements. Clinical examination and focal-electroretinogram-(fERG- derived macular (18° flicker sensitivity estimate (Falsini et al. (2010 every three months over a followup of 14 (±2 months. Retinal sensitivity, the reciprocal value of the estimated fERG amplitude threshold, was the main outcome measure. Results. After three months of supplementation, mean fERG sensitivity improved by 0.3 log units compared to baseline values (P<0.01, and mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, P<0.01. These changes remained stable over the follow-up period. Conclusion. These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term followup.

  14. External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient?

    International Nuclear Information System (INIS)

    Staar, Susanne; Krott, Ralf; Mueller, Rolf-Peter; Bartz-Schmidt, Karl U.; Heimann, Klaus

    1999-01-01

    Purpose: Control of the natural course of sub retinal neovascularization (SRNV) in age-related macular degeneration (AMD) is difficult. Only a subset of patients is suitable for laser coagulation. This prospective study aimed to determine the efficacy and individual benefit of external beam radiotherapy (EBRT). Methods and Materials: The prospective trial included 287 patients with subfoveal neovascularization due to AMD which was verified by fluorescein angiography. Patients have been treated between January 1996 and October 1997. All patients received a total dose of 16 Gy in 2-Gy daily fractions with 5-6 MeV photons based on computerized treatment planning in individual head mask fixation. This first analysis is based on 73 patients (50 women, 23 men, median age 74.3 years), with a median follow-up of 13.3 months and a minimum follow-up of 11 months. Results: All patients completed therapy and tolerability was good. First clinical control with second angiography was performed 6 weeks after irradiation, then in 3-month intervals. Eighteen patients with SRNV refusing radiotherapy served as a control group and were matched with 18 irradiated patients. After 7 months median visual acuity (VA) was 20/160 for the irradiated and 20/400 for the untreated patients. One year after radiotherapy final median VA was 20/400 in both groups. Conclusion: These results suggest that 16 Gy of conventionally fractionated external beam irradiation slows down the visual loss in exudative AMD for only a few months. Patients' reading vision could not be saved for a long-term run

  15. Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

    Science.gov (United States)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L; Khawaja, Anthony P; Cougnard-Gregoire, Audrey; Merle, Bénédicte M J; Korb, Christina; Erke, Maja G; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T V M; Vingerling, Johannes R; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E; Foster, Paul J; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C W

    2017-12-01

    Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Meta-analysis of prevalence data. A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Prevalence of early and late AMD, BCVA, and number of AMD cases. Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. We observed a decreasing prevalence of AMD and an improvement

  16. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

    Directory of Open Access Journals (Sweden)

    John Paul SanGiovanni

    Full Text Available Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs and use of peroxisome proliferator activator receptor (PPAR-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG co-activator 1 alpha (PPARGC1A, a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR transcription complex, may influence neovascularization (NV in age-related macular degeneration (AMD.We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A.A DNA coding variant (rs3736265 and a 3'UTR-resident regulatory variant (rs3774923 in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs. SNP-SNP interactions existed for NV AMD (P<0.005 with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559. PPARGC1A influences activation of the AMD-associated complement component 3 (C3 promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003 of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033, a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678 showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003. C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice

  17. Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

    International Nuclear Information System (INIS)

    Montserrat-de la Paz, S.; Naranjo, M.C.; Bermúdez, B.; López, S.; Abia, R.; Muriana, F.J.G.

    2017-01-01

    Age-related macular degeneration (AMD) is a medical condition of central loss vision and blindness. Numerous studies have revealed that changes on certain dietary fatty acids (FAs) could have useful for AMD management. This review summarizes the effects of dietary omega-3 long-chain PUFAs, MUFAs, and SFAs, and lipoproteins on AMD. Findings are consistent with the beneficial role of dietary omega-3 long-chain PUFAs, while the effects of dietary MUFAs and SFAs appeared to be ambiguous with respect to the possible protection from MUFAs and to the possible adverse impact from SFAs on AMD. Some of the pathological mechanisms associated with lipoproteins on AMD share those observed previously in cardiovascular diseases. It was also noticed that the effects of FAs in the diet and lipoprotein on AMD could be modulated by genetic variants. From a population health perspective, the findings of this review are in favour of omega-3 long-chain FAs recommendations in a preventive and therapeutic regimen to attain lower AMD occurrence and progression rates. Additional long-term and short-term nutrigenomic studies are required to clearly establish the role and the relevance of interaction of dietary FAs, lipoproteins, and genes in the genesis and progression of AMD. [es

  18. The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

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    Yafeng Wang

    2016-10-01

    Full Text Available Lipid metabolism may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with blood lipids. We performed a meta-analysis including a total of 19 studies to evaluate associations between blood lipids and this disease. The result reported that the high level of high-density lipoprotein cholesterol (HDL-C obtained with an increment of 1 mmol/L could result in a significantly increase in the AMD risk of approximately 18% (relative risk (RR, 1.18; 95% confidence interval (CI, 1.01 to 1.35; I2 = 53.8%; p = 0.007. High levels of total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and triglycerides (TG were significantly associated with a decreased risk of AMD (RRs ranging from 0.92 to 0.95; all p < 0.05. The stratified analysis based on AMD subtypes showed that these blood lipids were only significantly associated with the risk of early AMD (all p < 0.05. The association between the blood lipids and AMD risk did not differ substantially based on the other characteristics of the participants. A high HDL-C level was associated with an increased AMD risk, whereas participants with high TC, LDL-C, and TG concentrations may show a decreased risk for this disease. Further well-designed large studies are warranted to confirm the conclusions.

  19. Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    S. Montserrat-de la Paz

    2017-06-01

    Full Text Available Age-related macular degeneration (AMD is a medical condition of central loss vision and blindness. Numerous studies have revealed that changes on certain dietary fatty acids (FAs could have useful for AMD management. This review summarizes the effects of dietary omega-3 long-chain PUFAs, MUFAs, and SFAs, and lipoproteins on AMD. Findings are consistent with the beneficial role of dietary omega-3 long-chain PUFAs, while the effects of dietary MUFAs and SFAs appeared to be ambiguous with respect to the possible protection from MUFAs and to the possible adverse impact from SFAs on AMD. Some of the pathological mechanisms associated with lipoproteins on AMD share those observed previously in cardiovascular diseases. It was also noticed that the effects of FAs in the diet and lipoprotein on AMD could be modulated by genetic variants. From a population health perspective, the findings of this review are in favour of omega-3 long-chain FAs recommendations in a preventive and therapeutic regimen to attain lower AMD occurrence and progression rates. Additional long-term and short-term nutrigenomic studies are required to clearly establish the role and the relevance of interaction of dietary FAs, lipoproteins, and genes in the genesis and progression of AMD.

  20. Applying the CONSORT and STROBE statements to evaluate the reporting quality of neovascular age-related macular degeneration studies.

    Science.gov (United States)

    Fung, Anne E; Palanki, Ram; Bakri, Sophie J; Depperschmidt, Eric; Gibson, Andrea

    2009-02-01

    To evaluate the quality of reporting in the neovascular age-related macular degeneration (nvAMD) literature by applying the Consolidated Standards for Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement writing standards. CONSORT and STROBE impact analysis; literature review. Phase III randomized controlled trials (RCTs) of verteporfin photodynamic therapy, pegaptanib, and ranibizumab, and interventional case studies of bevacizumab for nvAMD. A literature search identified eligible articles published before October 31, 2007. We assessed the report quality of Phase III RCTs using the CONSORT statement and case series publications using the STROBE statement, both with indicators relevant to nvAMD. Presence or absence of CONSORT or STROBE statement indicators. Seven publications of Phase III RCTs and 29 publications on bevacizumab interventional case studies for nvAMD met our inclusion criteria. Of 37 possible CONSORT writing guideline items, the mean report quality for RCTs was 30.6 (83%), with a range from 23 to 35 (65%-95%). Of 35 possible STROBE writing guideline items, the mean report quality grade for intravitreal bevacizumab case series was 23 (70%), with a range from 16 to 31 (46%-94%). Among the bevacizumab studies, more than 90% reported scientific background, drug dose and administration, baseline characteristics, unadjusted results, and adverse events. Fewer than 20% reported study size calculations, handling of missing data, or a discussion of bias. Since the adoption of the CONSORT standards by Ophthalmology and other journals in 1996, the reporting quality for RCTs has further improved among this cohort of nvAMD articles. On the other hand, no reporting standards for case series have existed until the recent publication of the STROBE statement. In this first application of the STROBE standards to ophthalmology, we found that the small interventional studies in our series had an average

  1. Serum levels of lipid metabolites in age-related macular degeneration

    OpenAIRE

    Orban, Tivadar; Johnson, William M.; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J.; Palczewski, Krzysztof

    2015-01-01

    Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4−/−Rdh8−/− mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decrea...

  2. Motion-generated optical information allows event perception despite blurry vision in AMD and amblyopic patients.

    Science.gov (United States)

    Pan, Jing Samantha; Li, Jingrong; Chen, Zidong; Mangiaracina, Emily A; Connell, Christopher S; Wu, Hongyuan; Wang, Xiaoye Michael; Bingham, Geoffrey P; Hassan, Shirin E

    2017-10-01

    Events consist of objects in motion. When objects move, their opaque surfaces reflect light and produce both static image structure and dynamic optic flow. The static and dynamic optical information co-specify events. Patients with age-related macular degeneration (AMD) and amblyopia cannot identify static objects because of weakened image structure. However, optic flow is detectable despite blurry vision because visual motion measurement uses low spatial frequencies. When motion ceases, image structure persists and might preserve properties specified by optic flow. We tested whether optic flow and image structure interact to allow event perception with poor static vision. AMD (Experiment 1), amblyopic (Experiments 2 and 3), and normally sighted observers identified common events from either blurry (Experiments 1 and 2) or clear images (Experiment 3), when either single image frames were presented, a sequence of frames was presented with motion masks, or a sequence of frames was presented with detectable motion. Results showed that with static images, but no motion, events were not perceived well by participants other than controls in Experiment 3. However, with detectable motion, events were perceived. Immediately following this and again after five days, participants were able to identify events from the original static images. So, when image structure information is weak, optic flow compensates for it and enables event perception. Furthermore, weakened static image structure information nevertheless preserves information that was once available in optic flow. The combination is powerful and allows events to be perceived accurately and stably despite blurry vision.

  3. Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

    Directory of Open Access Journals (Sweden)

    Wenxin Ma

    2009-11-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD.In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space.These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

  4. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

    Science.gov (United States)

    Heier, Jeffrey S; Kherani, Saleema; Desai, Shilpa; Dugel, Pravin; Kaushal, Shalesh; Cheng, Seng H; Delacono, Cheryl; Purvis, Annie; Richards, Susan; Le-Halpere, Annaig; Connelly, John; Wadsworth, Samuel C; Varona, Rafael; Buggage, Ronald; Scaria, Abraham; Campochiaro, Peter A

    2017-07-01

    Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 10 8 vector genomes (vg); cohort 2, 2 × 10 9 vg; cohort 3, 6 × 10 9 vg; and cohort 4, 2 × 10 10 vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 10 10 vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 10 10 vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 10 10 vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight decrease to

  5. Mediated-reality magnification for macular degeneration rehabilitation

    Science.gov (United States)

    Martin-Gonzalez, Anabel; Kotliar, Konstantin; Rios-Martinez, Jorge; Lanzl, Ines; Navab, Nassir

    2014-10-01

    Age-related macular degeneration (AMD) is a gradually progressive eye condition, which is one of the leading causes of blindness and low vision in the Western world. Prevailing optical visual aids compensate part of the lost visual function, but omitting helpful complementary information. This paper proposes an efficient magnification technique, which can be implemented on a head-mounted display, for improving vision of patients with AMD, by preserving global information of the scene. Performance of the magnification approach is evaluated by simulating central vision loss in normally sighted subjects. Visual perception was measured as a function of text reading speed and map route following speed. Statistical analysis of experimental results suggests that our magnification method improves reading speed 1.2 times and spatial orientation to find routes on a map 1.5 times compared to a conventional magnification approach, being capable to enhance peripheral vision of AMD subjects along with their life quality.

  6. Vitamin D and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Alfredo Garcia Layana

    2017-10-01

    Full Text Available In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD. Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

  7. Serum levels of lipid metabolites in age-related macular degeneration.

    Science.gov (United States)

    Orban, Tivadar; Johnson, William M; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J; Palczewski, Krzysztof

    2015-11-01

    Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD. © FASEB.

  8. AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor

    DEFF Research Database (Denmark)

    Hatse, Sigrid; Princen, Katrien; De Clercq, Erik

    2005-01-01

    suggested that the bis-macrocyclic structure was a prerequisite for anti-HIV activity. Now, we report that the N-pyridinylmethylene cyclam AMD3465, which lacks the structural constraints mentioned above, fully conserves all the biological properties of AMD3100. Like AMD3100, AMD3465 blocked the cell surface......3100, AMD3465 was even 10-fold more effective as a CXCR4 antagonist, while showing no interaction whatsoever with CCR5. As expected, AMD3465 proved highly potent against X4 HIV strains (IC50: 1-10 nM), but completely failed to inhibit the replication of CCR5-using (R5) viruses. In conclusion, AMD3465...

  9. Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations.

    Science.gov (United States)

    Stingl, Katarina; Schippert, Ruth; Bartz-Schmidt, Karl U; Besch, Dorothea; Cottriall, Charles L; Edwards, Thomas L; Gekeler, Florian; Greppmaier, Udo; Kiel, Katja; Koitschev, Assen; Kühlewein, Laura; MacLaren, Robert E; Ramsden, James D; Roider, Johann; Rothermel, Albrecht; Sachs, Helmut; Schröder, Greta S; Tode, Jan; Troelenberg, Nicole; Zrenner, Eberhart

    2017-01-01

    Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy). Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks). Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs

  10. Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations

    Directory of Open Access Journals (Sweden)

    Katarina Stingl

    2017-08-01

    Full Text Available Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy.Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640. Functional outcome measures included (1 screen-based standardized 2- or 4-alternative forced-choice (AFC tests of light perception, light localization, grating detection (basic grating acuity (BaGA test, and Landolt C-rings; (2 gray level discrimination; (3 performance during activities of daily living (ADL-table tasks.Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10 were discerned. Improvements (power ON vs. OFF of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled. The majority of adverse events

  11. The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

    Science.gov (United States)

    Akuffo, Kwadwo Owusu; Beatty, Stephen; Peto, Tunde; Stack, Jim; Stringham, Jim; Kelly, David; Leung, Irene; Corcoran, Laura; Nolan, John M

    2017-10-01

    The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration. In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry. There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P 0.05). Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

  12. Spectral-domain Optical Coherence Tomography Retinal and Choroidal Thickness Metric Repeatability in Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2016-01-01

    PURPOSE: To determine the intrasession repeatability of spectral-domain OCT (SDOCT)-derived macular retinal and choroidal metrics in patients with neovascular age-related macular degeneration (nAMD) in the Distance of Choroid Study (DOCS). DESIGN: Validity and reliability analysis. METHODS......: Enrolled patients underwent repeated SDOCT imaging using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). A single technician certified for clinical trials took 3 macular volume scans. Retinal thicknesses were calculated for each of the 9 Early Treatment Diabetic Retinopathy Study (ETDRS...... was 34.7 μm (95% CI 33.7-35.7 μm). CONCLUSIONS: This study suggests that a change of greater than 31 μm in Spectralis SDOCT-derived retinal thickness measurement of the central macular subfield and 35 μm in subfoveal choroidal thickness is necessary to detect true clinical change associated with disease...

  13. Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

    Science.gov (United States)

    Merle, Bénédicte M J; Buaud, Benjamin; Korobelnik, Jean-François; Bron, Alain; Delyfer, Marie-Noëlle; Rougier, Marie-Bénédicte; Savel, Hélène; Vaysse, Carole; Creuzot-Garcher, Catherine; Delcourt, Cécile

    2017-12-01

    In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. Age, sex, and type of medication predict the effect of anti-VEGF treatment on central retinal thickness in wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Bek T

    2018-03-01

    Full Text Available Toke Bek, Sidsel Ehlers Klug Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark Purpose: Randomized clinical trials studying the effects of VEGF inhibition on wet age-related macular degeneration (wAMD are designed so that the effects of individually varying risk factors on the treatment response are eliminated. The influence of these risk factors can be studied in large data sets from real-life experience.Patients and methods: All 2,255 patients diagnosed with wAMD requiring anti-VEGF treatment in at least one eye over more than 9 years in a defined Danish population with 0.9 million inhabitants were studied. The predictive value of eye laterality, sex, current smoking status, type of anti-VEGF compound, membrane position, membrane type, leakage area, number of injections, number of visits, age, time to follow-up, visual acuity, and central retinal thickness (CRT at baseline on change in CRT after three monthly injections with anti-VEGF compound followed by treatment pro re nata for up to 12 months was assessed.Results: After 12 months, 67 patients had died, 903 had had stable CRT for at least 6 months, and 1,285 patients had not achieved stable CRT. The reduction in CRT was -84.8±118.3 µm, whereas the increase in visual acuity was 2.2±14.7 Early Treatment Diabetic Retinopathy Study letters. The risk factors included contributed to 64% of the variation in CRT reduction. High age and high CRT at baseline predicted high CRT reduction, whereas more injections, treatment with ranibizumab, and male sex predicted a low CRT reduction.Conclusion: Age, sex, and type of anti-VEGF medication can be used to plan treatment and inform patients about the expected response of anti-VEGF treatment in wAMD. Keywords: wet AMD, anti-VEGF treatment, risk factors, real-life experience 

  15. Secondary Analyses of the Effects of Lutein/Zeaxanthin on Age-Related Macular Degeneration Progression AREDS2 Report No.3

    Science.gov (United States)

    Chew, Emily Y.; Clemons, Traci E.; SanGiovanni, John Paul; Danis, Ronald P; Ferris, Frederick L.; Elman, Michael J.; Antoszyk, Andrew; Ruby, Alan; Orth, David; Bressler, Susan B.; Fish, Gary; Hubbard, Baker; Klein, Michael; Chandra, Suresh; Blodi, Barbara; Domalpally, Amitha; Friberg, Thomas; Wong, Wai; Rosenfeld, Philip; Agron, Elvira; Toth, Cynthia; Bernstein, Paul; Sperduto, Robert

    2015-01-01

    The Age-Related Eye Disease Study (AREDS) formulation for treatment of age-related macular degeneration contains vitamins C, E, beta-carotene and zinc with copper. Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk of lung cancer from beta-carotene in smokers and former smokers. As previously reported in a secondary analysis, AREDS2 participants taking lutein/zeaxanthin with or without omega-3 long-chain polyunsaturated fatty 3 acids had a slightly lower progression rate to late AMD than participants not taking lutein/zeaxanthin. Objective To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. Design, Setting, Participants AREDS2, a multicenter, double-masked randomized trial, of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% had bilateral large drusen and 34% had large drusen and late AMD in one eye. Interventions In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to one of the following four groups: placebo, lutein/zeaxanthin (10mg/2mg), omega-3 long-chain polyunsaturated fatty 3 acids (1.0 g), or the combination. Main Outcome Measures Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. Results In exploratory analysis of lutein/zeaxanthin vs. no lutein/zeaxanthin, the HR the development of late AMD was 0.90 (95% CI: 0.82–0.99), p=0.04. Exploratory analyses of direct comparison of lutein/zeaxanthin vs. beta-carotene showed HRs: 0.82 (95% CI: 0.69–0.96), p=0.02 for development of late AMD, 0.78 (95% CI: 0.64–0.94) p=0.01 for development of neovascular AMD, and 0.94 (95% CI: 0.70–1.26), p=0.67 for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein

  16. Influence of ROBO1 and RORA on risk of age-related macular degeneration reveals genetically distinct phenotypes in disease pathophysiology.

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    Gyungah Jun

    Full Text Available ROBO1 is a strong candidate gene for age-related macular degeneration (AMD based upon its location under a linkage peak on chromosome 3p12, its expression pattern, and its purported function in a pathway that includes RORA, a gene previously associated with risk for neovascular AMD. Previously, we observed that expression of ROBO1 and RORA is down-regulated among wet AMD cases, as compared to their unaffected siblings. Thus, we hypothesized that contribution of association signals in ROBO1, and interaction between these two genes may be important for both wet and dry AMD. We evaluated association of 19 single nucleotide polymorphisms (SNPs in ROBO1 with wet and dry stages of AMD in a sibling cohort and a Greek case-control cohort containing 491 wet AMD cases, 174 dry AMD cases and 411 controls. Association signals and interaction results were replicated in an independent prospective cohort (1070 controls, 164 wet AMD cases, 293 dry AMD cases. The most significantly associated ROBO1 SNPs were rs1387665 under an additive model (meta P = 0.028 for wet AMD and rs9309833 under a recessive model (meta P = 6 × 10(-4 for dry AMD. Further analyses revealed interaction between ROBO1 rs9309833 and RORA rs8034864 for both wet and dry AMD (interaction P<0.05. These studies were further supported by whole transcriptome expression profile studies from 66 human donor eyes and chromatin immunoprecipitation assays from mouse retinas. These findings suggest that distinct ROBO1 variants may influence the risk of wet and dry AMD, and the effects of ROBO1 on AMD risk may be modulated by RORA variants.

  17. Imaging Polarimetry in Age-Related Macular Degeneration

    Science.gov (United States)

    Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

    2010-01-01

    PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

  18. Macular ganglion cell complex and retinal nerve fiber layer comparison in different stages of age-related macular degeneration.

    Science.gov (United States)

    Zucchiatti, Ilaria; Parodi, Maurizio Battaglia; Pierro, Luisa; Cicinelli, Maria Vittoria; Gagliardi, Marco; Castellino, Niccolò; Bandello, Francesco

    2015-09-01

    To employ optical coherence tomography (OCT) to analyze the morphologic changes in the inner retina in different categories of age-related macular degeneration (AMD). Observational cross-sectional study. Single-center study. Inclusion criteria were age over 50, diagnosis of Age-Related Eye Disease Study (AREDS) category 2 and 3, naïve neovascular AMD, and atrophic AMD. Healthy patients of similar age acted as a control group. Primary outcome measures were the changes in ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Secondary outcomes included modifications of rim area and cup-to-disc ratio. One hundred and thirty eyes of 130 patients were recruited: 26 eyes for AREDS category 2, 26 for AREDS category 3, 26 for neovascular AMD, 26 with atrophic AMD, and 26 controls. Mean peripapillary RNFL thickness was significantly lower in neovascular AMD, compared to controls (P = .004); peripapillary RNFL did not significantly vary among AREDS category 2 and 3 and atrophic AMD groups, compared to controls. Mean GCC thickness was higher in the control group, becoming progressively thinner up to neovascular and atrophic AMD groups (P < .0001). Rim area was significantly thinner in the neovascular AMD group compared with controls (P = .047); cup-to-disc ratio was higher in the neovascular AMD group compared with the control group (P = .047). This study demonstrates that eyes with neovascular AMD display reduced RNFL and GCC thickness. RNFL is partially spared in atrophic advanced AMD. The identification of alteration in RNFL and GCC thickness may reveal useful for future therapeutic implications. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

    Science.gov (United States)

    SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M; Stahl, Andreas; Clemons, Traci E; Chew, Emily Y; Smith, Lois E H

    2013-01-01

    Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (Pcomplement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice - these animals also showed 70% reduction in retinal NV (P

  20. Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ba J

    2015-09-01

    Full Text Available Jun Ba,1,2,* Run-Sheng Peng,2,* Ding Xu,1 Yan-Hong Li,1 Hui Shi,1,3 Qianyi Wang,1 Jing Yu11Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, 2Department of Cardiac Surgery, Institute of Cardiovascular Diseases of Fudan University, Affiliated Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*Co-first authors of this workAims: Age-related macular degeneration (AMD is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD.Methods: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA, retinal thickness, and lesion size were evaluated.Results: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR group and the intravitreal bevacizumab group (standard mean difference =-0.14, 95% confidence interval [CI] =-0.23 to -0.05. No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN can raise VA by 1.97 letters (weighted mean difference =1.97, 95% CI =0.14–3.794. Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference =2.74, 95% CI =0.26–5.21.Conclusion: The superiority remains unclear between IVR and

  1. Assessment of serum lipids in patients with age related macular degeneration from Pakistan

    International Nuclear Information System (INIS)

    Ambreen, F.; Qureshi, I. Z.

    2014-01-01

    Objective: To determine serum lipids in patients with age related macular degeneration from Pakistani population. Methods: The study was a cross sectional, randomized and case-control. Selected subjects ages were >50 years and were normotensive, non-diabetic with no family history of any such disease and no complication of posterior ocular chamber other than age related macular degeneration (AMD). Controls were age matched healthy individuals with no symptoms of AMD. Diagnosis of AMD was done through conventional diagnostic techniques by professional ophthalmologists. Serum samples were analyzed for total cholesterol, triglycerides, LDL and HDL using commercially available kits. Data were compared with Student's t-test. Pearson correlation was calculated for relationship between different parameters. P<0.05 was considered significant. Results: Compared to controls, AMD patients had significantly greater total cholesterol concentration (p<0.041), and power HDL/LDL ratio (p<0.038), while serum triglycerides, HDL and LDL were non-significantly different from control subjects. Total cholesterol in AMD patients was significantly correlated with TG, LDL and HDL (p<0.0001). Conclusion: The study indicates that high cholesterol might be a predictor of AMD and can be a diagnostic parameter. (author)

  2. NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Jiangyuan Gao

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE and Bruch’s membrane (BM in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA or choroidal neovascularization (CNV. As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

  3. An overview on age related macular degeneration and recent advances in its management

    Directory of Open Access Journals (Sweden)

    SOBIA N.

    2014-03-01

    Full Text Available Age-related macular degeneration (AMD is a condition characterized, in the early stages, by slow development and progression, absence of symptoms over a number of years, and extensive retinal deposits called drusen, often associated with pigmentary abnormalities (early AMD.There is strong and consistent evidence that increasing age, family history, obesity/high body mass index, and cataract surgery are associated with late AMD. Smoking is the strongest and most consistently found modifiable risk factor for late AMD.Age-related macular degeneration remains one of the most severe and profound disabilities encountered in medicine, particularly due to the loss of the central vision and the high economic burden it places on patients and societies.Recent advances in management of AMD is anti-angiogenic drugs. The identification of the crucial role played by vascular endothelial growth factor (VEGF in the pathogenesis of wet AMD hasallowed the development of VEGF-blocking agents such as bevacizumab, pegaptanib and ranibizumab.

  4. Assessment of Choroidal Microstructure and Subfoveal Thickness Change in Eyes With Different Stages of Age-Related Macular Degeneration.

    Science.gov (United States)

    Lu, Linna; Xu, Shiqiong; He, Fangling; Liu, Yan; Zhang, Yidan; Wang, Jing; Wang, Zhiliang; Fan, Xianqun

    2016-03-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness. Choroidal structural changes seem to be inevitable in AMD pathogenesis. Our study revealed associated choroidal microstructural changes in AMD eyes.The aim of the study was to compare choroidal microstructural changes in eyes with AMD of different stages.The study was a retrospective, cross-sectional case series.The participants comprised of 32 age-matched normal eyes as controls, and 26 fellow uninvolved eyes of intermediate/late AMD, 29 of early AMD, 28 of intermediate AMD, and 39 of late AMD.All subjects underwent comprehensive ophthalmologic examination. The choroid images, including subfoveal choroidal thickness, percentage of Sattler layer area, and en face images of the choroid, were obtained using spectral-domain optical coherence tomography.The main outcome measures were subfoveal choroidal thickness changes, percentage of Sattler layer area changes, and en face images of the choroid in AMD eyes.One hundred fifty-four eyes of 96 individuals with mean age of 67.1±9.2 years were included. The mean subfoveal choroidal thickness was 295.4 ± 56.8 μm in age-matched normal eyes, 306.7 ± 68.4 μm in fellow uninvolved eyes with AMD, 293.8 ± 80.4 μm in early AMD, 215.6 ± 80.4 μm in intermediate AMD, and 200.4 ± 66.6 μm in late AMD (F = 14.2, all P < 0.001). Choroidal thickness was greater in early AMD eyes than in intermediate/late AMD eyes (P < 0.001). Mean percentage of Sattler layer area in each group showed a similar tendency. Microstructure of the choroid showed reduced vascular density of Sattler layer areas in late AMD eyes compared with normal eyes.Decreasing subfoveal choroidal thickness and percentage of Sattler layer area were demonstrated in the progression of AMD. The choroidal change was related to atrophy of the microstructural changes of underlying capillaries and medium-sized vessels.

  5. Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Purpose: The chemokine receptor CXCR3 has been strongly related to inhibition of angiogenesis. The purpose of this study was to investigate the association between expression of CXCR3 on peripheral blood leukocytes and Age-related Wet Macular Degeneration (AMD). Furthermore, we measured the plasma...... leading to choroidal neovascularisation (CNV) formation and growth. CXCR3-enhancing molecules could therefore be a possible target for treatment of AMD....

  6. PHOTODYNAMIC THERAPY OF MACULAR DEGENERATION

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    Davorin Sevšek

    2004-05-01

    Full Text Available Background. University Eye Clinic in Ljubljana began to perform a photodynamic therapy (PDT in July 2002. Up to September 2003 there were 51 PDT interventions on 36 eyes. Almost half of the eyes had one or more reinterventions. PDT was used on 29 eyes with age related macular degeneration (AMD. Just before the treatment all of them had visual acuity (VA 6/60 or better and there were predominantly classical or classical choroidal neovascular (CNV membranes. Most VA did not changed significantly in follow-up visits but diameter of CNV membranes was obviously reduced. In macular degeneration due to pathologic myopia (MMD, photodynamic therapy was performed on 7 eyes with mainly occult CNV and VA was 12/60 or better. VA was mostly better in follow-up visits than before treatment with PDT.Conclusions. There were no serious complications during and after PDT interventions. Two patients had back pain during the infusion of Verteporfin but there was no need to stop the intervention.

  7. Interactive Image Analysis in Age-related Macular Degeneration (AMD) and Stargardt Disease (STGD).

    Science.gov (United States)

    Smith, R Theodore; Lee, Noah; Chen, Jian; Busuioc, Mihai; Laine, Andrew F

    2008-10-26

    The literature of the last three decades is replete with automatic methods for retinal image analysis. Acceptance has been limited due to post-processing or tuning requirements that may be just as time consuming as the original manual methods. The point of view herein is that by taking advantage of the human visual system and expert knowledge from the outset, the promised efficiencies of digital methods can be achieved in practice as well as in theory. Thus, simple labeling of regions of interest that is accepted and easily performed in a few moments by the human can provide enormous advantage to an already well-developed algorithm. Three examples are provided: drusen segmentation, image registration, and geographic atrophy segmentation, with applications to disease understanding.

  8. Oral Bisphosphonates and Risk of Wet Age-Related Macular Degeneration.

    Science.gov (United States)

    Mammo, Zaid; Guo, Michael; Maberley, David; Matsubara, Joanne; Etminan, Mahyar

    2016-08-01

    To examine the risk of age-related macular degeneration (AMD) with oral bisphosphonates. Three study designs were used: (1) disproportionality analysis; (2) case-control study; (3) self-controlled case series (SCCS). setting: (1) Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Database; (2) 2 patient cohorts from British Columbia, Canada. (1) All reports of AMD to the FDA with oral bisphosphoantes; (2) patients with wet AMD in British Columbia (2009-2013) and 1 million controls (2000-2007). Oral bisphosphonates. (1) Reports of AMD to the FDA; (2) first diagnosis of wet AMD verified by a retina specialist in British Columbia. In the disproportionality analysis there were 133 cases of AMD reported with alendronate, 20 with ibandronate, and 14 with risedronate. The reported odds ratios (RORs) for alendronate, ibandronate, and risedronate were 3.82 (95% CI: 2.94-4.96), 2.40 (95% CI: 1.49-3.86), and 2.87 (95% CI: 1.58-5.19), respectively. In the case-control analysis there were 6367 cases and 6370 corresponding controls. The adjusted OR for wet AMD among regular users of bisphosphonates in the 1, 2, and 3 years prior to the index date were 1.24 (1.12-1.38), 1.38 (1.22-1.56), and 1.59 (1.38-1.82), respectively. In the SCCS analysis there were 198 cases of wet AMD on continuous bisphosphonate therapy. The rate ratio for wet AMD for continuous bisphosphonate use was 1.99 (95% CI: 1.41-2.79). We did not have information on intravenous bisphosphonates. Continuous users of oral bisphosphonates are at a higher risk of developing wet AMD. Given the observational nature of this study and limitation of the data, future studies are needed to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Impact of eye-tracking technology on OCT-angiography imaging quality in age-related macular degeneration.

    Science.gov (United States)

    Lauermann, J L; Treder, M; Heiduschka, P; Clemens, C R; Eter, N; Alten, F

    2017-08-01

    To evaluate the impact of eye-tracking (ET) technology on optical coherence tomography angiography (OCT-A) image quality and manifestation of motion artifacts in patients with age-related macular degeneration (AMD). In a prospective trial, multimodal retinal imaging including OCT-A was performed in 30 patients (78.97 ± 9.7 years) affected by different stages of AMD. Central 3 × 3 mm 2 OCT-A imaging was performed four times consecutively in each patient, twice with active, and twice with inactive ET. Parameters for image evaluation were signal strength index (SSI), variability of foveal vessel density (VD), acquisition time, presence of motion artifacts caused by eye movement (blink lines, displacement) and by software correction of eye movement (quilting, stretch artifacts, vessel doubling). Images were evaluated by two independent readers with subsequent senior reader arbitration for presence of artifacts, and an OCT-A motion artifact score (MAS) was calculated. Eight patients had early and eight patients had intermediate stages of AMD. Four patients had an atrophic late stage and ten patients an exudative stage of the disease. SSI was 53.55 with inactive and 57.18 with active ET (p = 0.0005). Coefficients of variability of VD between the first and second measurement were 8.9% with inactive and 5.7% with active ET. Mean image acquisition time was 15.97 s (active ET: 22.88 s, p < 0.001). Presence of motion artifacts was significantly higher with inactive ET (mean MAS 3.27 vs. 1.93; p < 0.0001). MAS correlated with AMD disease stage [p = 0.0031 (inactive ET) and p < 0.0001 (active ET)] and with SSI (p = 0.0072 and p = 0.0006). In patients with AMD, active ET technology offers an improved image quality in OCT-A imaging regarding presence of motion artifacts at the expense of higher acquisition time.

  10. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  11. Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?

    Science.gov (United States)

    Piechota, Malgorzata; Pawlowska, Elzbieta; Szatkowska, Magdalena; Sikora, Ewa; Kaarniranta, Kai

    2017-01-01

    Age-related macular degeneration (AMD) is the main reason of blindness in developed countries. Aging is the main AMD risk factor. Oxidative stress, inflammation and some genetic factors play a role in AMD pathogenesis. AMD is associated with the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillaris. Lost RPE cells in the central retina can be replaced by their peripheral counterparts. However, if they are senescent, degenerated regions in the macula cannot be regenerated. Oxidative stress, a main factor of AMD pathogenesis, can induce DNA damage response (DDR), autophagy, and cell senescence. Moreover, cell senescence is involved in the pathogenesis of many age-related diseases. Cell senescence is the state of permanent cellular division arrest and concerns only mitotic cells. RPE cells, although quiescent in the retina, can proliferate in vitro. They can also undergo oxidative stress-induced senescence. Therefore, cellular senescence can be considered as an important molecular pathway of AMD pathology, resulting in an inability of the macula to regenerate after degeneration of RPE cells caused by a factor inducing DDR and autophagy. It is too early to speculate about the role of the mutual interplay between cell senescence, autophagy, and DDR, but this subject is worth further studies. PMID:29225722

  12. Pluripotent stem cells: A therapeutic source for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Sowmya Parameswaran

    2017-01-01

    Full Text Available Age-related macular degeneration (AMD leads to progressive loss of central vision in the elderly. At a cellular level, there is aging of the retinal pigment epithelial (RPE cells, and accumulation of lipofuscin that interferes with the proper functioning of RPE which eventually leads to apoptosis. Treatment depends on the stage of the disease. Wet AMD which has neovascularization is managed by local therapies such as laser photocoagulation and photodynamic therapy and is managed with injections of antivascular endothelial growth factor-based therapy. Unlike the wet AMD, an effective therapy does not exist for dry AMD and geographic atrophy. Cell replacement therapy has shown promise. This review discusses the opportunities in the various types of cell-based therapy, their limitations, and what is possible for India.

  13. Knowledge discovery in ophthalmology: analysis of wet form of age-related macular degeneration treatment outcomes

    Science.gov (United States)

    Ulińska, Magdalena; Tataj, Emanuel; Mulawka, Jan J.; Szaflik, Jerzy

    2009-06-01

    Age-related Macular Degeneration (AMD), according to epidemiological data, is a main reason of social blindness among elderly people in developed countries. There are two forms of AMD: dry and wet. The first one is of good prognosis with low possibility of serious visual deterioration, while the second one usually leads to quick and severe visual impairment. The aim of our investigations is to analyse results of so called real-life treatment of wet AMD. We analysed outcomes of our patients treated with intravitreal injections of anti-VEGF drugs: Lucentis (61 patients) and Avastin (78 patients). We analysed changes in visual acuity (functional effect) and central retinal thickness (anatomic effect). Both drugs occurred to be efficient in treatment of wet form of AMD, however results were more satisfying in patients with better baseline visual acuity. In our approach we used R environment - an integrated suite of software facilities for data analysis and graphics.

  14. Review of graft rejection in age-related macular degeneration replacement therapy

    Directory of Open Access Journals (Sweden)

    Xi-Ying Mao

    2016-02-01

    Full Text Available Age-related macular degeneration(AMDis the leading cause of blindness among the elderly worldwide. AMD is classified as either neovascular(wetor non-neovascular(dry. The dysfunction and loss of retinal pigment epithelial(RPEcells is regarded as the main pathological changes of AMD. The recent development of regenerative medicine has witnessed RPE cell-replacement therapy as a new approach to treat AMD, resulting in obvious visual improvement in various studies. However, there are still many problems and challenges that remain unsolved, including graft rejection. This review introduces subretinal immune environment under both normal and AMD condition, putting emphasis on immune response to allogeneic RPE. Lastly, strategies to prevent graft rejection are discussed.

  15. Automated detection of age-related macular degeneration in OCT images using multiple instance learning

    Science.gov (United States)

    Sun, Weiwei; Liu, Xiaoming; Yang, Zhou

    2017-07-01

    Age-related Macular Degeneration (AMD) is a kind of macular disease which mostly occurs in old people,and it may cause decreased vision or even lead to permanent blindness. Drusen is an important clinical indicator for AMD which can help doctor diagnose disease and decide the strategy of treatment. Optical Coherence Tomography (OCT) is widely used in the diagnosis of ophthalmic diseases, include AMD. In this paper, we propose a classification method based on Multiple Instance Learning (MIL) to detect AMD. Drusen can exist in a few slices of OCT images, and MIL is utilized in our method. We divided the method into two phases: training phase and testing phase. We train the initial features and clustered to create a codebook, and employ the trained classifier in the test set. Experiment results show that our method achieved high accuracy and effectiveness.

  16. Description of nuclear structures in light nuclei with Brueckner-AMD

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    Katō K.

    2010-04-01

    Full Text Available We develop the new antisymmetrized molecular dynamics (AMD method, Brueckner-AMD, which makes us perform the AMD calculations starting from the realistic nuclear force. In the Brueckner-AMD, the single-particle orbits of AMD can be applied straightforward to the Bethe-Goldstone equation in the Brueckner theory by using the AMD+Hartree-Fock method, and the G-matrices are determined with the single-particle energies of AMD self-consistently. In that sense, in this framework, the G-matrix in AMD can be solved theoretically without any corrections. We present the applicability of the Brueckner-AMD to describe not only the ground states but also the excited states for some light nuclei, especially the excited 02+ state in 12C which is not solved sufficiently by the present shell model approaches, starting from the realistic nuclear force.

  17. A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration.

    Science.gov (United States)

    Simonett, Joseph M; Sohrab, Mahsa A; Pacheco, Jennifer; Armstrong, Loren L; Rzhetskaya, Margarita; Smith, Maureen; Geoffrey Hayes, M; Fawzi, Amani A

    2015-08-10

    Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMD-associated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects using electronic medical record (EMR)-based criteria. Positive predictive value (91.7%) and negative predictive value (97.5%) were calculated using expert chart review as the gold standard to assess algorithm performance. We applied the algorithm to an EMR-linked DNA bio-repository to study previously identified AMD-associated single nucleotide polymorphisms (SNPs), using case/control status determined by the algorithm. Risk alleles of three SNPs, rs1061170 (CFH), rs1410996 (CFH), and rs10490924 (ARMS2) were found to be significantly associated with the AMD case/control status as defined by the algorithm. With the rapid growth of EMR-linked DNA biorepositories, patient selection algorithms can greatly increase the efficiency of genetic association study. We have found that stepwise validation of such an algorithm can result in reliable cohort selection and, when coupled within an EMR-linked DNA biorepository, replicates previously published AMD-associated SNPs.

  18. Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

    Directory of Open Access Journals (Sweden)

    Yunus Bulgu

    2014-10-01

    Full Text Available AIM:To assess the association between age-related macular degeneration (AMD and three single nucleotide polymorphisms (SNPs related to the vascular endothelial growth factor (VEGF gene.METHODS: The patients who were diagnosed with AMD were included in this prospective study. Three SNPs (rs1413711, rs2146323, and rs3025033 of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS: The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group (P=0.072 and P=0.058. However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD (P=0.005 and P=0.010, respectively. One of the SNPs (rs1413711 was also found to be associated with the severity of AMD (P=0.001 with significant genotype distribution between early, intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION: VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

  19. Role of flicker perimetry in predicting onset of late-stage age-related macular degeneration.

    Science.gov (United States)

    Luu, Chi D; Dimitrov, Peter N; Robman, Luba; Varsamidis, Mary; Makeyeva, Galina; Aung, Khin-Zaw; Vingrys, Algis J; Guymer, Robyn H

    2012-06-01

    To investigate the longitudinal changes in flicker perimetry in patients with age-related macular degeneration (AMD) as the condition progresses from early AMD to geographic atrophy (GA) or choroidal neovascularization (CNV). Patients with AMD and control subjects were recruited from a longitudinal study of retinal function in early AMD consisting of 187 participants. Only those who completed at least 4 consecutive, 6-monthly flicker perimetry tests were selected for this study. Study groups consisted of everyone who went on to develop GA (n = 16) or CNV (n = 5), controls (n = 24), and the high-risk, early- AMD participants whose eyes did not progress to GA or CNV (drusen >125 μm; n = 18). The flicker sensitivity was determined, and its rate of change during the 18 months before the clinical detection of late AMD was calculated. Eyes that went on to develop GA or CNV had a significantly reduced mean (SD) flicker sensitivity in the months before clinical detection of GA (15.8 [5.6] dB) or CNV (19.1 [3.8] dB) compared with control eyes (22.9 [3.0] dB) (P flicker sensitivity was significantly increased in GA eyes (-0.07 dB/mo) (P Flicker sensitivity is reduced in eyes that go on to develop late AMD. The rate of change in flicker sensitivities over time was particularly useful in predicting eyes and areas within the eye that subsequently develop GA.

  20. The association between statin use and risk of age-related macular degeneration

    Science.gov (United States)

    Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

    2015-01-01

    The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

  1. [Summarize drug dosage forms in treatment of age-related macular degeneration disease].

    Science.gov (United States)

    Du, Mao-Bo; Liu, Shu-Zhi; Xu, Kai; Liang, Li-Na; He, Ai-Ping; Yao, Yao; Liu, Ya-Mei

    2017-02-01

    In this review, the authors summarized the drugs in treatment of the age-related macular degeneration (AMD or ARMD), including the pathogenesis of the age-related macular degeneration at home and abroad, dosage forms used in the treatment, and the drugs research and development directions in the future. AMD disease is the third largest blinding diseases all over the world, with an incidence of 6.62%. The dosage form of the traditional medicine is mostly oral formulations, playing a role in body, while the newly dosage form is topical drug delivery formulation. Traditional Chinese medicine (TCM) has certain advantages in the treatment of AMD disease and the development of topical drug delivery preparations with newly preparation technologies would have a very bright prospect in the future. Copyright© by the Chinese Pharmaceutical Association.

  2. Macular degeneration (image)

    Science.gov (United States)

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  3. American Macular Degeneration Foundation

    Science.gov (United States)

    ... Policy Disclaimer Contact Us Donate Store The American Macular Degeneration Foundation The American Macular Degeneration Foundation (AMDF) is ... Ed Asner Video Clip An Inspiring Her-story Macular Degeneration is the leading cause of vision loss, affecting ...

  4. Decision Support System for Age-Related Macular Degeneration Using Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Mostafa Langarizadeh

    2017-09-01

    Full Text Available Introduction: Age-related macular degeneration (AMD is one of the major causes of visual loss among the elderly. It causes degeneration of cells in the macula. Early diagnosis can be helpful in preventing blindness. Drusen are the initial symptoms of AMD. Since drusen have a wide variety, locating them in screening images is difficult and time-consuming. An automated digital fundus photography-based screening system help overcome such drawbacks. The main objective of this study was to suggest a novel method to classify AMD and normal retinal fundus images. Materials and Methods: The suggested system was developed using convolutional neural networks. Several methods were adopted for increasing data such as horizontal reflection, random crop, as well as transfer and combination of such methods. The suggested system was evaluated using images obtained from STARE database and a local dataset. Results: The local dataset contained 3195 images (2070 images of AMD suspects and 1125 images of healthy retina and the STARE dataset comprised of 201 images (105 images of AMD suspects and 96 images of healthy retina. According to the results, the accuracies of the local and standard datasets were 0.95 and 0.81, respectively. Conclusion: Diagnosis and screening of AMD is a time-consuming task for specialists. To overcome this limitation, we attempted to design an intelligent decision support system for the diagnosis of AMD fundus using retina images. The proposed system is an important step toward providing a reliable tool for supervising patients. Early diagnosis of AMD can lead to timely access to treatment.

  5. Targeting modifiable risk factors in age-related macular degeneration in optometric practice in Sweden

    Directory of Open Access Journals (Sweden)

    Martin L

    2017-04-01

    Full Text Available Lene Martin1,2 1School of Health, Care and Social Welfare, Mälardalen University, Eskilstuna, Sweden; 2School of Health Sciences, City, University of London, London, UK Purpose: The purpose of this study was to investigate the extent to which ophthalmologists and optometrists in Sweden recommend the use of nutritional supplements, changes in diet, or smoking cessation to patients who are at risk of or with signs of age-related macular degeneration (AMD. In addition, this study also examined how these practitioners rate the strength of evidence for nutritional supplements in AMD management and which sources of information they consult to determine supplement recommendations for the prevention or treatment of AMD. Methods: This study implemented a cross-sectional design using data from a questionnaire. All Swedish optometrists and ophthalmologists who were registered in the membership databases of their respective professional organizations were invited to participate. The questionnaire contained 18 forced choice questions and one free text question and was organized into the following four sections: use of nutritional supplements, dietary advice, smoking and eye diseases, and strength of evidence and the sources of information regarding nutritional supplement interventions. Results: The response rate was 40.3% for optometrists and 5% for ophthalmologists. Optometrists were more likely than ophthalmologists to recommend nutritional supplements in AMD and provided significantly more advice about diet than did the ophthalmologists for both patients at risk for AMD and those with established disease. The ophthalmologists were more likely than the optometrists to rely on the findings from the age-related eye disease studies of AMD regarding treatment with and selection of supplements and to recommend smoking cessation. Conclusion: Common evidence-based strategies for AMD management among eye care professionals would presumably be beneficial for AMD

  6. The relationship of major American dietary patterns to age-related macular degeneration

    Science.gov (United States)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  7. Near-infrared reflectance imaging of neovascular age-related macular degeneration.

    NARCIS (Netherlands)

    Theelen, T.; Berendschot, T.T.; Hoyng, C.B.; Boon, C.J.F.; Klevering, B.J.

    2009-01-01

    PURPOSE: To evaluate various types of neovascular age-related macular degeneration (AMD) by near-infrared fundus reflectance (NIR) as compared to fundus fluorescein angiography (FFA) and to test NIR for assessment of leakage due to choroidal neovascularization (CNV). PATIENTS AND METHODS:

  8. Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration : The European Eye Study

    NARCIS (Netherlands)

    Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

    2017-01-01

    PURPOSE: To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. DESIGN: Cross-sectional, population-based epidemiologic study. PARTICIPANTS: Of 5060 randomly sampled people aged

  9. Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Holz, Frank G; Dugel, Pravin U.; Weissgerber, Georges

    2016-01-01

    Purpose To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). Design Six-month, phase 1/2, prospective, multicenter, double-masked, randomized...

  10. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Science.gov (United States)

    Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

  11. Mitigating health problems associated with AMD in South Africa

    CSIR Research Space (South Africa)

    Schachtschneider, K

    2012-03-01

    Full Text Available Acid mine drainage (AMD) is a serious threat to water quality in South Africa. Questions are being asked to South African government leaders as to what they are doing to mitigate the effects that South Africa’s mining industry is having...

  12. DEMONSTRATION OF AN INTEGRATED, PASSIVE BIOLOGICAL TREATMENT PROCESS FOR AMD

    Science.gov (United States)

    An innovative, cost-effective, biological treatment process has been designed by MSE Technology Applications, Inc. to treat acid mine drainage (AMD). A pilot-scale demonstration is being conducted under the Mine Waste Technology Program using water flowing from an abandoned mine ...

  13. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  14. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  15. Nitrogen metabolism and growth enhancement in tomato plants challenged with Trichoderma harzianum expressing the Aspergillus nidulans acetamidase amdS gene

    Directory of Open Access Journals (Sweden)

    Sara Domínguez

    2016-08-01

    Full Text Available Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in T. harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by i enhanced growth, ii increased carbon and nitrogen levels and iii a

  16. CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine/Chemokine Receptor Complex in Patients with AMD

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    PURPOSE: The chemokine receptors CX3CR1 and CCR2 have been implicated in the development of age-related macular degeneration (AMD). The evidence is mainly derived from experimental cell studies and murine models of AMD. The purpose of this study was to investigate the association between expression...... of CX3CR1 and CCR2 on different leukocyte subsets and AMD. Furthermore we measured the plasma levels of ligands CX3CL1 and CCL2. METHODS: Patients attending our department were asked to participate in the study. The diagnosis of AMD was based on clinical examination and multimodal imaging techniques...... positive correlation between CCR2 and CX3CR1 expression on CD8+ cells (r = 0.727, p = 0.0001). We found no difference in plasma levels of CX3CL1 and CCL2 among the groups. CONCLUSIONS: Our results show a down regulation of CX3CR1 on CD8+ cells; this correlated to a low expression of CCR2 on CD8+ cells...

  17. Multi-surface segmentation of OCT images with AMD using sparse high order potentials.

    Science.gov (United States)

    Oliveira, Jorge; Pereira, Sérgio; Gonçalves, Luís; Ferreira, Manuel; Silva, Carlos A

    2017-01-01

    In age-related macular degeneration (AMD), the quantification of drusen is important because it is correlated with the evolution of the disease to an advanced stage. Therefore, we propose an algorithm based on a multi-surface framework for the segmentation of the limiting boundaries of drusen: the inner boundary of the retinal pigment epithelium + drusen complex (IRPEDC) and the Bruch's membrane (BM). Several segmentation methods have been considerably successful in segmenting retinal layers of healthy retinas in optical coherence tomography (OCT) images. These methods are successful because they incorporate prior information and regularization. Nonetheless, these factors tend to hinder the segmentation for diseased retinas. The proposed algorithm takes into account the presence of drusen and geographic atrophy (GA) related to AMD by excluding prior information and regularization just valid for healthy regions. However, even with this algorithm, prior information and regularization still cause the oversmoothing of drusen in some locations. Thus, we propose the integration of local shape prior in the form of a sparse high order potentials (SHOPs) into the algorithm to reduce the oversmoothing of drusen. The proposed algorithm was evaluated in a public database. The mean unsigned errors, relative to the average of two experts, for the inner limiting membrane (ILM), IRPEDC and BM were 2.94±2.69, 5.53±5.66 and 4.00±4.00 µ m, respectively. Drusen areas measurements were evaluated, relative to the average of two expert graders, by the mean absolute area difference and overlap ratio, which were 1579.7 ± 2106.8 µ m 2 and 0.78 ± 0.11, respectively.

  18. Switch to aflibercept or ranibizumab after initial treatment with bevacizumab in eyes with neovascular AMD.

    Science.gov (United States)

    Waizel, Maria; Todorova, Margarita G; Masyk, Michael; Wolf, Katharina; Rickmann, Annekatrin; Helaiwa, Khaled; Blanke, Björn R; Szurman, Peter

    2017-05-23

    To evaluate changes in central macular thickness (CMT) and visual outcome in patients with neovascular age-related macular degeneration (AMD) treated initially with bevacizumab and subsequently switched to either aflibercept or ranibizumab. Observational clinical study was performed. We measured the structural outcome (CMT on SD-OCT; μm) and the visual outcome (best corrected visual acuity (BCVA); logMAR), as follows: before treatment (at baseline), following bevacizumab treatment (switch follow-up) and after switching from bevacizumab to aflibercept- or ranibizumab treatment (final follow-up, AG/, RG). From a total of 96 eyes treated with intravitreal injections of bevacizumab (10.5 ± 7.6 (mean ± SD)), 58 eyes switched to aflibercept (6.5 ± 3.9; AG) and 38 eyes switched to ranibizumab (7.1 ± 5.3; RG) (≥ 3 injections, each). In addition, these eyes were compared to 37 eyes under bevacizumab monotherapy. In the AG, the CMT decreased slightly from 430 ± 220 μm at baseline to 419 ± 212 μm at switch follow-up (p = 0.86), but decreased significantly to 318 ± 159 μm at final follow-up, AG (p bevacizumab to either aflibercept, or ranibizumab, has a strong anatomical effect in eyes with neovascular AMD. Nevertheless, even if the switch to aflibercept shows a minimal functional benefit over that to ranibizumab, visual prognosis remains limited.

  19. The Association Between Subretinal Drusenoid Deposits in Older Adults in Normal Macular Health and Incident Age-Related Macular Degeneration.

    Science.gov (United States)

    Huisingh, Carrie; McGwin, Gerald; Neely, David; Zarubina, Anna; Clark, Mark; Zhang, Yuhua; Curcio, Christine A; Owsley, Cynthia

    2016-02-01

    Subretinal drusenoid deposits (SDD) have been associated with the progression to late age-related macular degeneration (AMD). To determine whether SDD in eyes in normal macular health increases risk for early AMD, this study examined the association between presence of SDD at baseline in a cohort of older adults in normal macular health and incident AMD 3 years later. Subjects enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) were assessed for the presence of SDD using color fundus photos, infrared reflectance and fundus autofluorescence images, and spectral-domain optical coherence tomography volumes. The study sample included 799 eyes from 455 participants in normal macular health per grading of color fundus photographs using the 9-step Age-Related Eye Disease Study (AREDS) classification system. Age-related macular degeneration was defined as eyes having an AREDS grade ≥2 at the 3-year follow-up. Twenty-five percent of participants had SDD in one or both eyes at baseline. At follow-up visit, 11.9% of eyes in the sample developed AMD. Compared to eyes without SDD, those with SDD were 2.24 (95% confidence interval [CI] 1.36-3.70) times more likely to have AMD at follow-up. After adjusting for age, C-reactive protein quartile, and family history of AMD, the association persisted. Results suggest that SDD in older eyes with normal macular health as defined by the AREDS scale is a risk factor for the development of early AMD. Older adults in seemingly normal macular health yet having SDD may warrant closer clinical monitoring for the possible onset of early AMD.

  20. Refractive Error and the Risk of Age-Related Macular Degeneration in the South Korean Population.

    Science.gov (United States)

    Lin, Shuai-Chun; Singh, Kuldev; Chao, Daniel L; Lin, Shan C

    2016-01-01

    We investigated the association between refractive error and the prevalence of age-related macular degeneration (AMD) in a population-based study. This was a cross-sectional study. Right eyes were included from 14,067 participants aged 40 years and older with gradable fundus photographs and refraction data from the fourth and the fifth Korea National Health and Nutrition Examination Survey 2008 to 2011. Early and late AMD was graded based on the International Age-Related Maculopathy Epidemiological Study Group grading system. Autorefraction data were collected to calculate spherical equivalent refraction in diopters (D) and classified into 4 groups: hyperopia (≥1.0 D), emmetropia (-0.99 to 0.99 D), mild myopia (-1.0 to -2.99 D), and moderate to high myopia (≤-3.0 D). After adjustment for potential confounders, each diopter increase in spherical equivalent was associated with a 16% [odds ratio (OR), 1.16; 95% confidence interval (CI), 1.08-1.25] and 18% (OR, 1.18; 95% CI, 1.10-1.27) increased risk of any (early + late) and early AMD, respectively. Mild and moderate to high myopia were associated with lower odds of any and early AMD compared with hyperopia (any AMD: OR, 0.62; 95% CI, 0.4-0.95 for mild myopia; OR, 0.41; 95% CI, 0.21-0.81 for moderate to high myopia; early AMD: OR, 0.63; 95% CI, 0.4-0.99 for mild myopia; OR, 0.36; 95% CI, 0.16-0.77 for moderate to high myopia group). There was no association between refractive status and the likelihood of late AMD (P = 0.91). Myopia is associated with lower odds of any and early AMD, but not with late AMD in the South Korean population.

  1. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Evans Christopher

    2010-12-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. Methods A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR and/or relative risk (RR outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI were calculated. Results Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Conclusions Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.

  2. Rate of adjacent segment degeneration of cervical disc arthroplasty versus fusion Meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Luo, Jiaquan; Wang, Hongbo; Peng, Jun; Deng, Zhongyuan; Zhang, Zhen; Liu, Shixue; Wang, Daidong; Gong, Ming; Tang, Shuo

    2018-02-27

    The concern of adjacent segment disease (ASD) has led to the development of motion-preserving technologies such as cervical disc arthroplasty (CDA). However, there is still controversy whether CDA is superior to anterior cervical decompression and fusion (ACDF) as to the incidence of ASD. The purpose of this study is to evaluate the rate of ASD between CDA and ACDF. Systematic searches of all relevant studies through November. 2017 were identified from Cochrane Library, PubMed, Embase and CNKI. Randomized controlled trials (RCTs) comparing clinical effectiveness of CDA and ACDF for cervical DDD were included. Two independent reviewers searched and assessed all literature according to the standard of Cochrane systematic review.Data extraction and quality assessment were conducted, and RevMan 5.2 was used for data analysis. The random effects model was used if there was heterogeneity between studies; otherwise, the fixed effects model was used. A total of 21 studies were included in our meta-analysis. The pooled data revealed that CDA group had significantly lower adjacent segment diseases than that in the ACDF group. Furthermore, there were fewer adjacent segment reoperations in the CDA group compared with the ACDF group. Based on this meta-analysis, we conclude that CDA was better than the ACDF in terms of ASD and adjacent segment reoperations. This suggests the HS is a superior alternative invention for the treatment of cervical DDD to preserve cervical range of motion and reduce the risk of ASD. However, this requires further validation and investigation in larger sample-size prospective and randomized studies with long-term follow-up. Copyright © 2018. Published by Elsevier Inc.

  3. Mendelian Randomization Implicates High-Density Lipoprotein Cholesterol-Associated Mechanisms in Etiology of Age-Related Macular Degeneration.

    Science.gov (United States)

    Burgess, Stephen; Davey Smith, George

    2017-08-01

    Undertake a systematic investigation into associations between genetic predictors of lipid fractions and age-related macular degeneration (AMD) risk. Two-sample Mendelian randomization investigation using published data. A total of 33 526 individuals (16 144 cases, 17 832 controls) predominantly of European ancestry from the International Age-related Macular Degeneration Genomics Consortium. We consider 185 variants previously demonstrated to be associated with at least 1 of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides at a genome-wide level of significance, and test their associations with AMD. We particularly focus on variants in gene regions that are proxies for specific pharmacologic agents for lipid therapy. We then conduct a 2-sample Mendelian randomization investigation to assess the causal roles of LDL-cholesterol, HDL-cholesterol, and triglycerides on AMD risk. We also conduct parallel investigations for coronary artery disease (CAD) (viewed as a positive control) and Alzheimer's disease (a negative control) for comparison. Diagnosis of AMD. We find evidence that HDL-cholesterol is a causal risk factor for AMD, with an odds ratio (OR) estimate of 1.22 (95% confidence interval [CI], 1.03-1.44) per 1 standard deviation increase in HDL-cholesterol. No causal effect of LDL-cholesterol or triglycerides was found. Variants in the CETP gene region associated with increased circulating HDL-cholesterol also associate with increased AMD risk, although variants in the LIPC gene region that increase circulating HDL-cholesterol have the opposite direction of association with AMD risk. Parallel analyses suggest that lipids have a greater role for AMD compared with Alzheimer's disease, but a lesser role than for CAD. Some genetic evidence suggests that HDL-cholesterol is a causal risk factor for AMD risk and that increasing HDL-cholesterol (particularly via CETP inhibition) will increase AMD risk

  4. Association of OCT-Derived Drusen Measurements with AMD-Associated Genotypic SNPs in the Amish Population

    Directory of Open Access Journals (Sweden)

    Venkata Ramana Murthy Chavali

    2015-02-01

    Full Text Available Purpose: To investigate the association of optical coherence tomography (OCT-derived drusen measures in Amish age-related macular degeneration (AMD patients with known loci for macular degeneration. Methods: Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE atrophy using a Cirrus High-Definition OCT. Measurements were obtained in the macula region within a central circle (CC of 3 mm in diameter and a surrounding perifoveal ring (PR of 3 to 5 mm in diameter using the Cirrus OCT RPE analysis software. Other demographic information, including age, gender and smoking status, were collected. Study subjects were further genotyped to determine their risk for the AMD-associated SNPs in the SYN3, LIPC, ARMS2, C3, CFB, CETP, CFI and CFH genes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models. Results: 432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for the drusen area (the area increased 0.12 mm2 for a risk allele increase, p < 0.01, drusen volume (the volume increased 0.01 mm3 for a risk allele increase, p ≤ 0.05 and the area of RPE atrophy (the area increased 0.43 mm2 for a risk allele increase, p = 0.003. SYN3 risk allele G is significantly associated with larger area PR (the area increased 0.09 mm2 for a risk allele increase, p = 0.03 and larger drusen volume in the central circle (the volume increased 0.01 mm3 for a risk allele increase, p = 0.04. Conclusion: Among the genotyped SNPs tested, the CFH risk genotype appears to play a major role in determining the drusen phenotype in the Amish AMD population.

  5. Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.

    Science.gov (United States)

    Laíns, Inês; Kelly, Rachel S; Miller, John B; Silva, Rufino; Vavvas, Demetrios G; Kim, Ivana K; Murta, Joaquim N; Lasky-Su, Jessica; Miller, Joan W; Husain, Deeba

    2018-02-01

    To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). Cross-sectional observational study. We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10 -9 ) among these metabolites. Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest

  6. Age-related macular degeneration and cognitive impairment show similarities in changes of neutral lipids in peripheral blood mononuclear cells.

    Science.gov (United States)

    Peiretti, Enrico; Mandas, Antonella; Abete, Claudia; Vinci, Michela; Piludu, Stefania; Casu, Maura; Caminiti, Giulia; Dessì, Sandra; Fossarello, Maurizio

    2014-07-01

    Starting from previous studies showing that patients with cognitive deficit present neutral lipids (NLs) accumulation in cytoplasm of their peripheral blood mononuclear cells (PBMCs) and considering that there is epidemiological evidence linking age-related macular degeneration (AMD) to cognitive deficit, the first purpose of this study was to test whether neutral lipids also accumulated in PBMCs from AMD subjects. Moreover, the impact of statin use on AMD was explored and whether such use in AMD subjects was associated with NLs accumulation in PBMCs. The study was conducted on 222 subjects: 136 AMD (36 of which - 26.5% - using statins], 48 cognitive deficit (20 of which - 41.7% - using statins) and 38 healthy controls (4 of which -10.1% - using statins), AMD lesions were assessed from color fundus photographs. Mini-mental state examination (MMSE), demographics, lifestyle factors and medical history were collected at interview. MMSE score was categorized as normal (24-30), and impaired (<24), NLs content was evaluated by oil red 0 (ORO) staining method. ORO determination showed that neutral lipids were generally absent or very low (score between 0 and 1) in healthy controls while most of PBMCs from cognitive deficit and AMD had ORO staining levels scoring 2-4. Post hoc analysis (Bonferroni) in a one-way ANOVA revealed that ORO score was significantly higher in cognitive deficit and AMD subjects compared to healthy controls and in cognitive deficit compared to AMD. Bonferroni-test also showed that AMD subjects had significantly lower total cholesterol (TC) levels compared to healthy controls while high density lipoprotein-cholesterol (HDL-C) did not reach statistical significance. The results also revealed a significant higher number of statin-users in AMD compared to healthy controls. Likewise when cognitive deficit vs healthy controls was analyzed, the number of statin users were found to be significant higher in cognitive deficit than in healthy controls. There

  7. Identification of Age-Related Macular Degeneration Using OCT Images

    Science.gov (United States)

    Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

    2018-02-01

    Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

  8. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.

    Science.gov (United States)

    Berner, Andre K; Kleinman, Mark E

    2016-01-01

    Recent data have revealed epigenetic derangements and subsequent chromatin remodeling as a potent biologic switch for chronic inflammation and cell survival which are important therapeutic targets in the pathogenesis of several retinal degenerations. Histone deacetylases (HDACs) are a major component of this system and serve as a unique control of the chromatin remodeling process. With a multitude of targeted HDAC inhibitors now available, their use in both basic science and clinical studies has widened substantially. In the field of ocular biology, there are data to suggest that HDAC inhibition may suppress neovascularization and may be a possible treatment for retinitis pigmentosa and dry age-related macular degeneration (AMD). However, the effects of these inhibitors on cell survival and chemokine expression in the chorioretinal tissues remain very unclear. Here, we review the multifaceted biology of HDAC activity and pharmacologic inhibition while offering further insight into the importance of this epigenetic pathway in retinal degenerations. Our laboratory investigations aim to open translational avenues to advance dry AMD therapeutics while exploring the role of acetylation on inflammatory gene expression in the aging and degenerating retina.

  9. ROCK-Isoform-Specific Polarization of Macrophages Associated with Age-Related Macular Degeneration

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    Souska Zandi

    2015-02-01

    Full Text Available Age is a major risk factor in age-related macular degeneration (AMD, but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.

  10. Generation and characterization of ABBV642, a dual variable domain immunoglobulin molecule (DVD-Ig) that potently neutralizes VEGF and PDGF-BB and is designed for the treatment of exudative age-related macular degeneration.

    Science.gov (United States)

    Ding, Kun; Eaton, Lucia; Bowley, Diana; Rieser, Matthew; Chang, Qing; Harris, Maria C; Clabbers, Anca; Dong, Feng; Shen, Jikui; Hackett, Sean F; Touw, Debra S; Bixby, Jacqueline; Zhong, Suju; Benatuil, Lorenzo; Bose, Sahana; Grinnell, Christine; Preston, Gregory M; Iyer, Ramesh; Sadhukhan, Ramkrishna; Marchie, Susan; Overmeyer, Gary; Ghayur, Tariq; van Riet, Deborah A; Tang, Shibo; Campochario, Peter A; Gu, Jijie

    Exudative age-related macular degeneration (AMD) is the most common cause of moderate and severe vision loss in developed countries. Intraocular injections of vascular endothelial growth factor (VEGF or VEGF-A)-neutralizing proteins provide substantial benefit, but frequent, long-term injections are needed. In addition, many patients experience initial visual gains that are ultimately lost due to subretinal fibrosis. Preclinical studies and early phase clinical trials suggest that combined suppression of VEGF and platelet-derived growth factor-BB (PDGF-BB) provides better outcomes than suppression of VEGF alone, due to more frequent regression of neovascularization (NV) and suppression of subretinal fibrosis. We generated a dual variable domain immunoglobulin molecule, ABBV642 that specifically and potently binds and neutralizes VEGF and PDGF-BB. ABBV642 has been optimized for treatment of exudative AMD based on the following design characteristics: 1) high affinity binding to all VEGF-A isoforms and both soluble and extracellular matrix (ECM)-associated PDGF-BB; 2) potential for extended residence time in the vitreous cavity to decrease the frequency of intraocular injections; 3) rapid clearance from systemic circulation compared with molecules with wild type Fc region for normal FcRn binding, which may reduce the risk of systemic complications; and 4) low risk of potential effector function. The bispecificity of ABBV642 allows for a single injection of a single therapeutic agent, and thus a more streamlined development and regulatory path compared with combination products. In a mouse model of exudative AMD, ABBV642 was observed to be more effective than aflibercept. ABBV642 has potential to improve efficacy with reduced injection frequency in patients with exudative AMD, thereby reducing the enormous disease burden for patients and society.

  11. Adjacent segment degeneration after lumbar spinal fusion: the impact of anterior column support: a randomized clinical trial with an eight- to thirteen-year magnetic resonance imaging follow-up.

    Science.gov (United States)

    Videbaek, Tina S; Egund, Niels; Christensen, Finn B; Grethe Jurik, Anne; Bünger, Cody E

    2010-10-15

    Randomized controlled trial. To analyze long-term adjacent segment degeneration (ASD) after lumbar fusion on magnetic resonance imaging and compare randomization groups with and without anterior column support. ASD can be a long-term complication after fusion. The prevalence and the cause of ASD are not well documented, but ASD are one of the main arguments for introducing the use of motion-preserving techniques as an alternative to fusion. Anterior lumbar interbody fusion combined with posterolateral lumbar fusion (ALIF+PLF) has been proved superior to posterolateral fusion alone regarding outcome and cost-effectiveness. Between 1996 and 1999, 148 patients with severe chronic low back pain were randomly selected for ALIF+PLF or for PLF alone. Ninety-five patients participated. ASD was examined on magnetic resonance imaging with regard to disc degeneration, disc herniation, stenosis, and endplate changes. Disc heights on radiographs taken at index surgery and at long-term follow-up were compared. Outcome was assessed by validated questionnaires. The follow-up rate was 76%. ASD was similar between randomization groups. In the total cohort, endplate changes were seen in 26% of the participants and correlated significantly with the presence of disc degeneration and disc herniation. Disc degeneration and dorsal disc herniation were the parameters registered most frequently and were significantly more pronounced at the first adjacent level than at the second and the third adjacent levels. Patients without disc height reduction over time were significantly younger than patients with disc height reduction. Disc degeneration and stenosis correlated significantly with outcome at the first adjacent level. The cause of the superior outcome in the group with anterior support is still unclear. Compared with the findings reported in the literature, the prevalence of ASD is likely to be in concordance with the expected changes in a nonoperated symptomatic population and therefore

  12. The controversy over the association between statins use and progression of age-related macular degeneration: a mini review

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    Vasileios Peponis

    2010-07-01

    Full Text Available Vasileios Peponis1, Spyridon E Chalkiadakis1, Stefanos Bonovas2,3, Nikolaos M Sitaras21Athens Eye Hospital, 2nd Eye Clinic, Athens, Greece; 2Department of Pharmacology, School of Medicine, University of Athens, Greece; 3Center for Diseases Control and Prevention, Athens, GreeceObjective: Age-related macular degeneration (AMD is the leading cause of blindness in ¬western societies. Statins comprise a class of pharmacological agents that reduce plasma cholesterol levels, and have been shown to prevent progression of atherosclerosis and reduce cardiovascular mortality. The relationship between these medications and AMD has been evaluated in several recent studies. Herein, we examine the current evidence for an association between statin use and risk of AMD.Methods: Literature database search (Medline, Scopus, and Science Citation Index Expanded for articles published up to March 2010, using particular search terms.Results: From the current evidence available, it is not safe to conclude upon the assumption of a protective effect of statins against age-related maculopathy and AMD.Conclusion: There is a need for large scale prospective studies with a long follow-up period and accurate assessment of AMD to further explore this matter.Keywords: age-related macular degeneration (AMD, blindness, statin use, controversy

  13. Education, socio-economic status and age-related macular degeneration in Asians: the Singapore Malay Eye Study.

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    Cackett, P; Tay, W T; Aung, T; Wang, J J; Shankar, A; Saw, S M; Mitchell, P; Wong, T Y

    2008-10-01

    Low socio-economic status is increasingly being identified as a risk marker for chronic diseases, but few studies have investigated the link between socio-economic factors and age-related macular degeneration (AMD). The present study aimed to assess the association between socio-economic status and the prevalence of AMD. A population-based cross-sectional study of 3280 (78.7% response rate) Malay adults aged 40-80 years residing in 15 south-western districts of Singapore. AMD was graded from retinal photographs at a central reading centre using the modified Wisconsin AMD scale. Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Socio-economic status including education, housing type and income were determined from a detailed interview. Of the participants, 3265 had photographs of sufficient quality for grading of AMD. Early AMD was present in 168 (5.1%) and late AMD in 21 (0.6%). After adjusting for age, gender, smoking, hypertension, diabetes and body mass index, participants with lower educational levels were significantly more likely to have early AMD (multivariate OR 2.2, 95% CI 1.2 to 4.0). This association was stronger in persons who had never smoked (multivariate OR 3.6, 95% confidence CI 1.4 to 9.4). However, no association with housing type or income was seen. Low educational level is associated with a higher prevalence of early AMD signs in our Asian population, independent of age, cardiovascular risk factors and cigarette smoking.

  14. Peripapillary Retinal Nerve Fiber Measurement with Spectral-Domain Optical Coherence Tomography in Age-Related Macular Degeneration

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    Simon K. Law

    2017-12-01

    Full Text Available Purpose: To evaluate the relationship between the peripapillary retinal nerve fiber layer (RNFL measurements with Spectral-domain Optical Coherence Tomography (OCT and Age-related macular degeneration (AMD. Methods: Patients >60 years of age without glaucoma or record of intraocular pressure >21 mmHg and no systemic or intraocular diseases or treatment or surgical intervention that affected the RNFL underwent OCT measurement of the RNFL. The severity of AMD was staged with the Clinical Age-Related Maculopathy Staging System. The relationship between RNFL measurements and AMD stages of one eye per patient was analyzed. Results: Eighty-six eyes (46 patients with AMD and no glaucoma or other exclusion criteria received OCT RNFL measurements. Nine eyes (10.5% were excluded because of distorted peripapillary anatomy from exudative AMD (7 eyes or failure of the RNFL segmentation algorithm (2 eyes. Mean age ± S.D. of the 43 patients analyzed was 81.2 ± 7.3 years. The mean stage ± S.D. of AMD of the 77 eyes was 3.77 ± 1.05. Higher stages of AMD were statistically significantly associated with lower average RNFL and inferior sector RNFL (p = 0.049, 0 0015, respectively. The association of inferior sector RNFL and AMD stage remained statistically significant after adjusting for age. Conclusions: Spectral domain OCT is generally useful in measuring the peripapillary RNFL in eyes with different stages of AMD. Higher stage of AMD is associated with thinner peripapillary RNFL, which may masquerade as early glaucomatous damage.

  15. Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

    Science.gov (United States)

    Adamus, Grazyna

    2017-03-01

    Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease, there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood is necessary. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.

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    John Paul SanGiovanni

    Full Text Available We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1-based signaling pathway that converges on DNA-binding transcription complexes through a 3'-5'-cyclic adenosine monophosphate-calcineurin (cAMP-CN-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P ≤ 9.48 x 10(-5, DCC (Deleted in Colorectal Cancer--the gene encoding a primary NTN1 receptor (rs8097127, P ≤ 3.03 x 10(-5, and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038, supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD.

  17. Automated age-related macular degeneration classification in OCT using unsupervised feature learning

    Science.gov (United States)

    Venhuizen, Freerk G.; van Ginneken, Bram; Bloemen, Bart; van Grinsven, Mark J. J. P.; Philipsen, Rick; Hoyng, Carel; Theelen, Thomas; Sánchez, Clara I.

    2015-03-01

    Age-related Macular Degeneration (AMD) is a common eye disorder with high prevalence in elderly people. The disease mainly affects the central part of the retina, and could ultimately lead to permanent vision loss. Optical Coherence Tomography (OCT) is becoming the standard imaging modality in diagnosis of AMD and the assessment of its progression. However, the evaluation of the obtained volumetric scan is time consuming, expensive and the signs of early AMD are easy to miss. In this paper we propose a classification method to automatically distinguish AMD patients from healthy subjects with high accuracy. The method is based on an unsupervised feature learning approach, and processes the complete image without the need for an accurate pre-segmentation of the retina. The method can be divided in two steps: an unsupervised clustering stage that extracts a set of small descriptive image patches from the training data, and a supervised training stage that uses these patches to create a patch occurrence histogram for every image on which a random forest classifier is trained. Experiments using 384 volume scans show that the proposed method is capable of identifying AMD patients with high accuracy, obtaining an area under the Receiver Operating Curve of 0:984. Our method allows for a quick and reliable assessment of the presence of AMD pathology in OCT volume scans without the need for accurate layer segmentation algorithms.

  18. Effects of Magnification on Emotion Perception in Patients With Age-Related Macular Degeneration.

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    Johnson, Aaron P; Woods-Fry, Heather; Wittich, Walter

    2017-05-01

    Individuals with low vision often experience difficulties in performing tasks of daily living, such as face perception. This leads them to having difficulties with social interactions, as they can no longer correctly perceive the emotion of others. The present study investigated the effects of magnification on face perception in participants with age-related macular degeneration (AMD), and their ability to detect and categorize emotions. It was hypothesized that patients with AMD would be less accurate in comparison to healthy controls, but that magnification would improve their performance to that of controls. Faces containing happy, angry, or neutral emotion were both doubled (equivalent of arm's length distance) and decreased by half in size (equivalent of across the street). The ability to detect and to discriminate emotional content was compared between 20 AMD patients and 7 age-matched controls. Eye movements were recorded while conducting both tasks. Regardless of stimulus size, when compared to controls, we observed that individuals with AMD consistently performed with lower accuracy in both emotion detection and categorization tasks. Moreover, having images undergo a 2-fold increase in size did improve performance, but did not equate AMD participants' performance to that of the controls in either the emotion detection or categorization task. Eye movements in AMD participants were highly variable in position compared to controls. The data suggest that magnification alone does not appear to be the answer for improving emotion perception within individuals with low vision. Next steps should include an evaluation of the effects of viewing strategy.

  19. Prevalence of and risk factors for age-related macular degeneration in a multiethnic Asian cohort.

    Science.gov (United States)

    Cheung, Chui Ming Gemmy; Tai, E Shyong; Kawasaki, Ryo; Tay, Wan Ting; Lee, Jeannette L; Hamzah, Haslina; Wong, Tien Y

    2012-04-01

    To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed. Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (Chinese men. The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

  20. Dietary folate, B vitamins, genetic susceptibility and progression to advanced nonexudative age-related macular degeneration with geographic atrophy: a prospective cohort study.

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    Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

    2016-04-01

    There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value. We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility. Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, complement component 2, complement component 3, complement factor B, collagen type VIII α 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses. There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the complement component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying the risk allele (G) (P = 0.76). Neither

  1. Is Age-Related Macular Degeneration Associated with Stroke Among Elderly Americans?§

    Science.gov (United States)

    Liao, Duanping; Mo, Jingping; Duan, Yinkang; Klein, Ronald; Scott, Ingrid U; Huang, Kui A; Zhou, Haibo

    2008-01-01

    Objective: To investigate whether age-related macular degeneration (AMD) is associated with the development of ischemic and hemorrhagic stroke among elderly Americans. Design: Population-based cohort study. Participants: The five percent random sample of 2000-2003 Medicare enrollees was obtained. The cohort (n=1,519,086) consisted of enrollees who were aged 65 or older at the first two-year (January 1, 2000 to December 31, 2001). Methods: Baseline demographic variables and chronic conditions (AMD and type, history of myocardial infarction (MI), stroke, hypertension, and diabetes) were defined based on the occurrence of relevant ICD-9 codes in relevant diagnosis fields of the baseline Medicare Data. We excluded 215,900 persons who had a diagnosis of MI or stroke during baseline period to form a cohort of 1,303,186 individuals who were free of major cardio-cerebral vascular disease (CVD) at baseline. Main Outcome Measures: In two years of follow-up (January 1, 2002 to December 31, 2003), a total of 89,501 incident stroke cases were identified, including 80,018 ischemic, 7048 hemorrhagic, and 2,435 stroke cases of both types. Results: Baseline mean age was 75 years (Standard Divination=7.7), with 60% women and 88% whites. The prevalence of AMD was 10.6%, with 19.7% being neovascular AMD and 80.3% being non-neovascular AMD. Baseline age, gender, race, hypertension, and diabetes adjusted 2-year incident odds ratios and 95% confidence internal of stroke associated with AMD were 1.31 (1.26, 1.36) for neovascular AMD, 1.18 (1.15, 1.21) for non-neovascular AMD, and 1.21 (1.18, 1.23) for either neovascular or non-neovascular AMD. Conclusion: The findings are suggestive of an association between AMD, especially neovascular AMD, and incident stroke, independent of demographic factors and co-morbidity. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables not measured in this study, suggest the possibility of shared common

  2. Is age-related macular degeneration associated with stroke among elderly americans?

    Science.gov (United States)

    Liao, Duanping; Mo, Jingping; Duan, Yinkang; Klein, Ronald; Scott, Ingrid U; Huang, Kui A; Zhou, Haibo

    2008-03-08

    To investigate whether age-related macular degeneration (AMD) is associated with the development of ischemic and hemorrhagic stroke among elderly Americans. Population-based cohort study. The five percent random sample of 2000-2003 Medicare enrollees was obtained. The cohort (n=1,519,086) consisted of enrollees who were aged 65 or older at the first two-year (January 1, 2000 to December 31, 2001). Baseline demographic variables and chronic conditions (AMD and type, history of myocardial infarction (MI), stroke, hypertension, and diabetes) were defined based on the occurrence of relevant ICD-9 codes in relevant diagnosis fields of the baseline Medicare Data. We excluded 215,900 persons who had a diagnosis of MI or stroke during baseline period to form a cohort of 1,303,186 individuals who were free of major cardio-cerebral vascular disease (CVD) at baseline. In two years of follow-up (January 1, 2002 to December 31, 2003), a total of 89,501 incident stroke cases were identified, including 80,018 ischemic, 7048 hemorrhagic, and 2,435 stroke cases of both types. Baseline mean age was 75 years (Standard Divination=7.7), with 60% women and 88% whites. The prevalence of AMD was 10.6%, with 19.7% being neovascular AMD and 80.3% being non-neovascular AMD. Baseline age, gender, race, hypertension, and diabetes adjusted 2-year incident odds ratios and 95% confidence internal of stroke associated with AMD were 1.31 (1.26, 1.36) for neovascular AMD, 1.18 (1.15, 1.21) for non-neovascular AMD, and 1.21 (1.18, 1.23) for either neovascular or non-neovascular AMD. The findings are suggestive of an association between AMD, especially neovascular AMD, and incident stroke, independent of demographic factors and co-morbidity. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables not measured in this study, suggest the possibility of shared common antecedents between stroke and AMD.

  3. Variability in depressive symptoms predicts cognitive decline in age-related macular degeneration.

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    Rovner, Barry W; Casten, Robin J; Leiby, Benjamin E

    2009-07-01

    The measurement of affective symptoms in older persons who decline cognitively is uncertain. The authors investigated whether mood variability predicts dementia in patients with age-related macular degeneration (AMD). Three-year observational study after a clinical trial. Community follow-up of outpatients ascertained from retina clinics. One hundred sixty patients with AMD. Geriatric Depression Scale (GDS) administered every 2 weeks for 6 months to subjects; Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to subjects' knowledgeable informants. Twenty-three subjects (14.4%) declined cognitively. Age, education, baseline GDS score > or =5, and variability in GDS scores (i.e., fluctuations between adjacent time points) were associated with cognitive decline. For GDS variability, each 1 unit increase in the residual standard deviation (SD) of the GDS increased the risk for cognitive decline by 93% (IDR = 1.92; 95% CI [1.27-2.91]). Thus, subjects with a residual SD of 1 were nearly twice as likely to become demented as subjects with no variability in GDS scores. The risk for subjects with SDs of 2 increased more than threefold (IDR = 3.68; 95% CI [1.61-8.47]). A multiple regression analysis showed that GDS variability was a significant risk factor for dementia after controlling for significant covariates. These data suggest a useful approach to conceptualizing and measuring depressive symptoms in older persons. Variability in self-reported mood may be an early sign of dementia and may offer new insights into the neurobiological mechanisms linking depression and cognition

  4. Complement Factor H Y402H and LOC387715 A69S Polymorphisms in Association with Age-Related Macular Degeneration in Iran.

    Science.gov (United States)

    Nazari Khanamiri, Hossein; Ghasemi Falavarjani, Khalil; Sanati, Mohammad Hossein; Aryan, Hajar; Irani, Alireza; Hashemi, Masih; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Nikeghbali, Aminollah

    2014-04-01

    To determine the frequency of complement factor H (Y402H) and age related macular degeneration susceptibility gene 2 (A69S) single nucleotide polymorphisms in patients with age-related macular degeneration (AMD) and in matched non-AMD controls in an Iranian population. Seventy patients with AMD and 86 age- and sex-matched controls were recruited and examined. Peripheral blood sample was obtained from all subjects for DNA extraction and direct sequencing of Y402H and A69S genes. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association of Y402H and A69S polymorphisms with AMD were determined. The frequencies of both homozygous and heterozygous genotypes were significantly higher in cases than controls for both Y402H and A69S polymorphisms. In comparison to the wild genotypes, OR for AMD associated with Y402H and A69S polymorphisms were 1.9 (95% CI, 1.1-3.2) and 2.2 (95%CI, 1.6-3.1), respectively. Joint risk analysis considering both genes revealed a higher risk of AMD when polymorphisms were present for both genes. Y402H and A69S polymorphisms were strongly associated with AMD in this Iranian population.

  5. Complement Factor H Y402H and LOC387715 A69S Polymorphisms in Association with Age-Related Macular Degeneration in Iran

    Directory of Open Access Journals (Sweden)

    Hossein Nazari Khanamiri

    2014-01-01

    Full Text Available Purpose: To determine the frequency of complement factor H (Y402H and age related macular degeneration susceptibility gene 2 (A69S single nucleotide polymorphisms in patients with age-related macular degeneration (AMD and in matched non-AMD controls in an Iranian population. Methods: Seventy patients with AMD and 86 age- and sex-matched controls were recruited and examined. Peripheral blood sample was obtained from all subjects for DNA extraction and direct sequencing of Y402H and A69S genes. Odds ratios (ORs with 95% confidence intervals (CIs for the association of Y402H and A69S polymorphisms with AMD were determined. Results: The frequencies of both homozygous and heterozygous genotypes were significantly higher in cases than controls for both Y402H and A69S polymorphisms. In comparison to the wild genotypes, OR for AMD associated with Y402H and A69S polymorphisms were 1.9 (95% CI, 1.1-3.2 and 2.2 (95%CI, 1.6-3.1, respectively. Joint risk analysis considering both genes revealed a higher risk of AMD when polymorphisms were present for both genes. Conclusion: Y402H and A69S polymorphisms were strongly associated with AMD in this Iranian population.

  6. The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

    Directory of Open Access Journals (Sweden)

    Stefano Lazzeri

    2012-01-01

    Full Text Available In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377 of VEGF-A receptor-2 (VEGFR-2 gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33% in patients with AMD than in the control subjects (34.62%; P=0.0095, chi-square test; Pcorr=0.038; OR=0.42, 95% CI 0.22 to 0.82. In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  7. Prevalence of Age-Related Macular Degeneration in Nakuru, Kenya: A Cross-Sectional Population-Based Study

    Science.gov (United States)

    Mathenge, Wanjiku; Bastawrous, Andrew; Peto, Tunde; Leung, Irene; Foster, Allen; Kuper, Hannah

    2013-01-01

    Background Diseases of the posterior segment of the eye, including age-related macular degeneration (AMD), have recently been recognised as the leading or second leading cause of blindness in several African countries. However, prevalence of AMD alone has not been assessed. We hypothesized that AMD is an important cause of visual impairment among elderly people in Nakuru, Kenya, and therefore sought to assess the prevalence and predictors of AMD in a diverse adult Kenyan population. Methods and Findings In a population-based cross-sectional survey in the Nakuru District of Kenya, 100 clusters of 50 people 50 y of age or older were selected by probability-proportional-to-size sampling between 26 January 2007 and 11 November 2008. Households within clusters were selected through compact segment sampling. All participants underwent a standardised interview and comprehensive eye examination, including dilated slit lamp examination by an ophthalmologist and digital retinal photography. Images were graded for the presence and severity of AMD lesions following a modified version of the International Classification and Grading System for Age-Related Maculopathy. Comparison was made between slit lamp biomicroscopy (SLB) and photographic grading. Of 4,381 participants, fundus photographs were gradable for 3,304 persons (75.4%), and SLB was completed for 4,312 (98%). Early and late AMD prevalence were 11.2% and 1.2%, respectively, among participants graded on images. Prevalence of AMD by SLB was 6.7% and 0.7% for early and late AMD, respectively. SLB underdiagnosed AMD relative to photographic grading by a factor of 1.7. After controlling for age, women had a higher prevalence of early AMD than men (odds ratio 1.5; 95% CI, 1.2–1.9). Overall prevalence rose significantly with each decade of age. We estimate that, in Kenya, 283,900 to 362,800 people 50 y and older have early AMD and 25,200 to 50,500 have late AMD, based on population estimates in 2007. Conclusions AMD is an

  8. Risk factors for neovascular age-related macular degeneration. The Eye Disease Case-Control Study Group.

    Science.gov (United States)

    1992-12-01

    Neovascular age-related macular degeneration (AMD) is one of five retinal disorders studied in the Eye Disease Case-Control Study. Data were obtained from 421 patients with neovascular AMD and 615 controls on a broad array of possible risk factors through interviews, clinical examinations, and laboratory analyses of blood samples. Decreased risk of neovascular AMD was associated with higher levels of carotenoids in the serum samples, higher horizontal cup-to-disc ratios, and use of postmenopausal exogenous estrogens in women. Increased risk of neovascular AMD was associated with cigarette smoking, higher levels of serum cholesterol, and parity greater than zero. No support was found for sunlight exposure, serum zinc levels, or iris color as risk factors for this disease. Although no association was found with a history of cardiovascular disease itself, the associations with postmenopausal exogenous estrogen use, cigarette smoking, and serum cholesterol level are consistent with a hypothesis linking risk factors for cardiovascular disease with neovascular AMD. The association noted between serum carotenoid levels and neovascular AMD supports the hypothesis that higher levels of micronutrients with antioxidant capabilities may decrease the risk of AMD.

  9. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Jiajia Chen

    2017-11-01

    Full Text Available Background/Aims: Age-related macular degeneration (AMD is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. Methods: We examined the CD4+ T cell compartments and their functions in AMD patients. Results: AMD patients presented significantly higher frequencies of interferon (IFN-γ-expressing and interleukin (IL-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. Conclusions: This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets.

  10. Prevalence and risk factors for age-related macular degeneration in Indians: a comparative study in Singapore and India.

    Science.gov (United States)

    Gemmy Cheung, Chui Ming; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B; Nangia, Vinay; Wong, Tien Yin

    2013-04-01

    To compare the prevalence and risk factors for age-related macular degeneration (AMD) in 2 Indian populations, 1 living in urban Singapore and 1 in rural central India. Population-based, cross-sectional studies of Indians aged 40+ years. Our analysis included 3337 Singapore-residing participants and 3422 India-residing participants. All participants underwent comprehensive systemic and ocular examinations and retinal photography. AMD was graded from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Systemic and ocular risk factors were assessed for association with AMD. Singapore-residing participants were older (mean age 57.8 years vs 53.8 years) and, after adjusting for age and sex, were more likely to have previous cataract surgery, higher body mass index, hypertension, diabetes, previous myocardial infarction, higher cholesterol, and lower creatinine levels, but less likely to be current smokers, than India-residing participants. The age-standardized prevalence of early and late AMD was 4.45% and 0.34%, respectively, in Singapore and 5.80% and 0.16%, respectively, in India. Shorter axial length was associated with early AMD in both Singapore and India, whereas previous cataract surgery, higher body mass index, hypertension, and lower cholesterol were associated with early AMD in Singapore but not in India. The prevalence of AMD was similar among Indian adults living in urban Singapore and rural India, despite differences in cardiovascular risk factor profile and demographics. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration.

    Science.gov (United States)

    Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

    2017-01-01

    Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. We examined the CD4+ T cell compartments and their functions in AMD patients. AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets. © 2017 The Author(s). Published by S. Karger AG, Basel.

  12. Relationship between HTRA1 polymorphism and genetic susceptibility of wet age-related macular degeneration in Han population

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    Nan Yang

    2018-05-01

    Full Text Available AIM: To investigate the relationship between high temperature essential factor A-1(HTRA1polymorphism and genetic susceptibility of wet age-related macular degeneration(AMDin Han population. METHODS: Totally 201 patients of wet AMD in Han population were selected from May 2014 to January 2017 in our hospital as disease group, and 201 healthy persons of Han were selected as health group. Blood samples of peripheral vein were collected and genomic DNA was extracted. HTRA1 polymorphism loci were detected, and the rs11200638 and rs2248799 loci of HTRA1 gene were detected by Sequenom mass spectrometry platform. Then the relationship between HTRA1 polymorphism and genetic susceptibility of wet AMD were analyzed. RESULTS: The grade distributions of the genotype of the rs11200638 and rs2248799 loci in the two groups subjects had significant differences(PPPOR values of rs11200638 genotype AA and AG were respectively 5.36 and 3.45, which were the risk factors of wet AMD(POR values of rs2248799 genotype TT and TC were respectively 2.36 and 1.98, which were the risk factors of wet AMD(PCONCLUSION: The rs11200638 and rs2248799 polymorphisms of HTRA1 gene are associated with the incidence of wet AMD, and the genotype AA and TT are closely related to the risk of wet AMD in Han population, of which the higher frequencies can increase the risk of wet AMD.

  13. T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

    2017-11-20

    Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

  14. Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Martina Barchitta

    2016-01-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963 and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs and 95% confidence intervals (95% CIs based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963.

  15. Biomarkers of oxidative stress in patients with wet age related macular degeneration.

    Science.gov (United States)

    Zafrilla, P; Losada, M; Perez, A; Caravaca, G; Mulero, J

    2013-03-01

    The aim of this study was to analyze biomarkers of oxidative stress in patients with wet age related macular degeneration (AMD). Case-control study that includes 163 patients with wet AMD (age group of 55-82 years with the mean age of 71 years and 170 age-matched healthy controls in the age group of 55-78 years with the mean age of 71 years. The following parameters were determined: reduced and oxidized Glutathione (GSH/GSSH), protein carbonyl groups, total antioxidant activity in plasma and the activity of endogenous antioxidant enzymes, such as, gluthatione peroxidase, gluthatione reductase and superoxide dismutase. We observed total antioxidant activity higher in control group (CG) compared with patients with wet AMD (7.1 ± 1.2 μM Trolox vs 5.8 ± 1.1 μM Trolox). Values of superoxide dismutase activity (SOD), gluthatione reductase (GR) and gluthatione peroxidase (GPx) are higher in control group than in patients with wet AMD. According to the GSH/GSSH results, average values were higher in the CG than in patients with wet AMD and data were not significantly different.. Values of protein carbonyl groups were higher in patients with wet AMD than in CG and significant differences were found. The finding of the present study suggests that the patients with wet AMD are an altered metabolic state of oxidation-reduction and that it is convenient to give therapeutic interventions with antioxidants. We have demonstrated that systematic oxidative stress, measured by different biomarkers is closely associated with the wet AMD.

  16. Prevalence of age-related macular degeneration in the Republic of Ireland.

    Science.gov (United States)

    Akuffo, Kwadwo Owusu; Nolan, John; Stack, Jim; Moran, Rachel; Feeney, Joanne; Kenny, Rose Anne; Peto, Tunde; Dooley, Cara; O'Halloran, Aisling M; Cronin, Hilary; Beatty, Stephen

    2015-08-01

    Age-related macular degeneration (AMD) remains the most common cause of visual loss among subjects over 50 years of age in the developed world. The Irish Longitudinal study on Ageing (TILDA) is a population-based study of subjects aged 50 years or older, designed to investigate factors that influence ageing, and has enabled this investigation of the prevalence of AMD in the Republic of Ireland (ROI). Data collected from a nationally representative sample of community-living older adults aged 50 years and over in ROI over the period November 2009 to July 2011. 5035 participants attended the TILDA health centre for assessment. Retinal photographs were obtained in 4859 of these participants. Retinal grading was performed in a masked fashion using a modified version of the International Classification and Grading System for AMD. Adjusting for lower response rates among older subjects, the estimated overall prevalence of any AMD was 7.2% (95% CI 6.5% to 7.9%) in the population aged 50 years or older. The estimated prevalence of early AMD was 6.6% (95% CI 5.9% to 7.3%), and the estimated prevalence of late AMD was 0.6% (95% CI 0.4% to 0.8%). Statistically significant associations with AMD included increasing age and family history of the condition. This is the first study to provide prevalence estimates of AMD in ROI and will inform eye care professionals and policymakers involved in the delivery and planning of care for those afflicted with this condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

    Science.gov (United States)

    Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

    2014-01-01

    Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

  18. Is Coffee Consumption associated with Age-related Macular Degeneration and Diabetic Retinopathy?

    Directory of Open Access Journals (Sweden)

    Neelam Kumari

    2014-03-01

    Full Text Available Introduction Coffee is among the most widely consumed beverages in the world. Several epidemiological studies have evaluated the association between coffee consumption and risk of systemic diseases; however, there is paucity of data in relation to coffee consumption and risk of eye diseases.  This study aims to examine the relationship between coffee consumption and risk of age-related macular degeneration (AMD and diabetic retinopathy (DR in multiethnic population of Singapore.   Materials and MethodsWe analyzed the data from 4121 study participants from the Singapore Prospective Study Program to examine the relationship of coffee to prevalence of AMD and DR.  A standardized questionnaire that included information about the habitual amount of coffee consumed was completed by all study participants.  Presence and severity of AMD and DR was assessed on fundus photographs using the Mutiethnic Study of Atherosclerosis Grading Protocol. ResultsThe prevalence of AMD and DR in our population was 5.4% and 32.0%, respectively. A positive history of coffee consumption was present in 77.5% of AMD population and 76.1% of DR population with majority of participants consuming 1-2 cups of coffee daily.  No statistically significant association was observed between coffee consumption and odds of AMD or DR after adjusting for confounding factors [AMD: Odds Ratio (OR = 1.27, Confidence Interval (CI = 0.88-1.83, p = 0.20; DR: OR = 1.36, CI = 0.69-2.69, p = 0.37.  ConclusionThis epidemiological study of a large multiethnic population data set do not support the hypothesis that habitual intake of coffee and caffeine is associated with an altered risk of AMD and DR among Asians.

  19. The ARMOUR Study: Anti-VEGF in Neovascular AMD--Our Understanding in a Real-World Indian Setting.

    Science.gov (United States)

    Jain, Nimesh; Yadav, Naresh Kumar; Jayadev, Chaitra; Srinivasan, Priya; Mohan, Ashwin; Shetty, Bhujang K

    2017-01-01

    The aim of our study was to share our experience with anti-vascular endothelial growth factor (anti-VEGF) injections in the treatment of neovascular age-related macular degeneration (nAMD) in a real-world setting. A retrospective, observational study. Patients of Indian origin with nAMD receiving anti-VEGF with a minimum follow-up of 12 months were enrolled in this study. In group 1, patients were treated on a pro re nata (PRN) basis; in group 2, patients received a loading dose (3 injecti Results: Overall, we observed that 77.31% (92/119 eyes) of patients either maintained or had improved visual acuity at 12 months' follow-up. Similar visual outcome was observed in both groups. The average number of injections given in group 1 was 4.98 and in group 2 was 3.7. CDVA at 12 months was significantly correlated with type of drug molecule, CSFT at 3 and 12 months, baseline visual acuity, and CDVA at 3 months. PRN treatment with significantly fewer injections achieved similar anatomical and functional outcomes when compared with the loading dose group. The results of this study need to be validated with a larger study group and a longer follow-up. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  20. The Aspergillus nidulans amdS gene as a marker for the identification of multicopy T-DNA integration events in Agrobacterium-mediated transformation of Aspergillus awamori

    NARCIS (Netherlands)

    Michielse, C.B.; Ram, A.F.J.; Hondel, C.A.M.J.J. van den

    2004-01-01

    The Aspergillus nidulans amdS selection marker was used for the identification of multicopy T-DNA insertions in Agrobacterium-mediated transformation of Asp. awamori. The selection of transformants on agar plates containing acetamide as sole nitrogen source and hygromycin resulted in a six-fold

  1. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

    NARCIS (Netherlands)

    L.G. Fritsche (Lars); W. Igl (Wilmar); J.N. Cooke Bailey (Jessica N.); F. Grassmann (Felix); S. Sengupta (Sebanti); J.L. Bragg-Gresham (Jennifer L.); Burdon, K.P. (Kathryn P.); S.J. Hebbring (Scott J.); Wen, C. (Cindy); M. Gorski (Mathias); I.K. Kim (Ivana); Cho, D. (David); Zack, D. (Donald); E.H. Souied (Eric); H.P.N. Scholl (Hendrik); E. Bala (Elisa); ELee, K. (Kristine); D. Hunter (David); Sardell, R.J. (Rebecca J.); P. Mitchell (Paul); J.E. Merriam (Joanna); F. Cipriani (Francesco); Hoffman, J.D. (Joshua D.); T. Schick (Tina); Y.T.E. Lechanteur (Yara T. E.); R.H. Guymer (Robyn); M.P. Johnson (Matthew); Y. Jiang; C.M. Stanton (Chloe); G.H.S. Buitendijk (Gabrielle); X. Zhan (Xiaowei); Kwong, A.M. (Alan M.); A. Boleda (Alexis); M. Brooks (Matthew); L. Gieser (Linn); R. Ratna Priya (Rinki); K.E. Branham (Kari); Foerster, J.R. (Johanna R.); J.R. Heckenlively (John); M.I. Othman (Mohammad); B.J. Vote (Brendan J.); Liang, H.H. (Helena Hai); E. Souzeau (Emmanuelle); McAllister, I.L. (Ian L.); T. Isaacs (Timothy); Hall, J. (Janette); Lake, S. (Stewart); D.A. Mackey (David); Constable, I.J. (Ian J.); J.E. Craig (Jamie E.); T.E. Kitchner (Terrie E.); Yang, Z. (Zhenglin); Su, Z. (Zhiguang); Luo, H. (Hongrong); Chen, D. (Daniel); Ouyang, H. (Hong); K. Flagg (Ken); Lin, D. (Danni); Mao, G. (Guanping); H.A. Ferreyra (Henry); K. Stark (Klaus); C. von Strachwitz (Claudia); Wolf, A. (Armin); C. Brandl (Caroline); Rudolph, G. (Guenther); M. Olden (Matthias); M.A. Morrison (Margaux); D.J. Morgan (Denise); M. Schu (Matthew); Ahn, J. (Jeeyun); G. Silvestri (Giuliana); E.E. Tsironi (Evangelia); Park, K.H. (Kyu Hyung); L.A. Farrer (Lindsay); A. Orlin (Anton); Brucker, A. (Alexander); X. Li (Xiaohui); C.A. Curcio (Christine A.); Mohand-Sa'd, S. (Saddek); J.-A. Sahel (José-Alain); I. Audo (Isabelle); M. Benchaboune (Mustapha); A.J. Cree (Angela); Rennie, C.A. (Christina A.); Goverdhan, S.V. (Srinivas V.); M. Grunin (Michelle); S. Hagbi-Levi (Shira); B. Campochiaro (Betsy); N. Katsanis (Nicholas); J.-B. Holz; F. Blond (Frédéric); Blanché, H. (Hél'ne); Deleuze, J.-F. (Jean-Fran'ois); R.P. Igo Jr. (Robert); B.J. Truitt (Barbara); N.S. Peachey (Neal ); S.M. Meuer (Stacy); C.E. Myers (Chelsea); Moore, E.L. (Emily L.); R. Klein (Ronald); M.A. Hauser (Michael); E.A. Postel (Eric); M.D. Courtenay (Monique D.); S.M. Schwartz (Stephen); J.L. Kovach (Jaclyn); W.K. Scott (William); Liew, G. (Gerald); Tan, A.G. (Ava G.); B. Gopinath (Bamini); J.E. Merriam (Joanna); T. Smith (Tim); J.C. Khan (Jane); M. Shahid (Mohammad); A.T. Moore (Anthony); J.A. McGrath (J Allie); R. Laux (Reneé); M.A. Brantley (Milam); A. Agarwal (Anita); L. Ersoy (Lebriz); A. Caramoy (Albert); T. Langmann (Thomas); N.T.M. Saksens (Nicole T.); Jong, E.K. (Eiko Kde); C. Hoyng (Carel); M.S. Cain (Melinda); A.J. Richardson (Andrea); T.M. Martin (Tammy M.); J. Blangero (John); D.E. Weeks (Daniel); Dhillon, B. (Bal); C.M. van Duijn (Cornelia); K.F. Doheny (Kimberly); Romm, J. (Jane); C.C.W. Klaver (Caroline); C. Hayward (Caroline); Gorin, M.B. (Michael B.); M.L. Klein (Michael); P.N. Baird (Paul); A.I. Hollander (Anneke); Fauser, S. (Sascha); WYates, J.R. (John R.); R. Allikmets (Rando); J.J. Wang (Jie Jin); D.A. Schaumberg (Debra); B.E.K. Klein (Barbara); S.A. Hagstrom (Stephanie); Y. Chowers (Yehuda); A.J. Lotery (Andrew); T. Léveillard (Thierry); K. Zhang (Kang); M.H. Brilliant (Murray H.); A.W. Hewit (Alex); A. Swaroop (Anand); Chew, E.Y. (Emily Y.); M.A. Pericak-Vance (Margaret); M.M. DeAngelis (Margaret); D. Stambolian (Dwight); J.L. Haines (Jonathan); S.K. Iyengar (Sudha); B.H.F. Weber (Bernhard); G.R. Abecasis (Gonçalo); I.M. Heid (Iris)

    2016-01-01

    textabstractAdvanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients

  2. Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients...

  3. Neovascular age-related macular degeneration without drusen in the fellow eye : clinical spectrum and therapeutic outcome

    NARCIS (Netherlands)

    Chung, Wing H; van Dijk, Elon H C; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K; Fauser, Sascha; Schlingemann, Reinier O; Hoyng, Carel B; Boon, Camiel J F

    2017-01-01

    PURPOSE: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. PATIENTS AND METHODS: Medical records of 381 patients were analyzed to identify the cases. The main outcomes

  4. Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome

    NARCIS (Netherlands)

    Chung, Wing H.; van Dijk, Elon H. C.; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K.; Fauser, Sascha; Schlingemann, Reinier O.; Hoyng, Carel B.; Boon, Camiel J. F.

    2017-01-01

    Purpose: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. Patients and methods: Medical records of 381 patients were analyzed to identify the cases. The main outcomes

  5. Neovascular age-related macular degeneration treated with ranibizumab or aflibercept in the same large clinical setting

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit; Larsen, Michael

    2017-01-01

    PURPOSE: To study visual outcome and number of annual injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) before and after a change in first-line therapy from ranibizumab to aflibercept in a high-volume clinical practice. METHODS: This was a retrospective...

  6. Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Purpose: The chemokine receptor CXCR3 has been strongly related to inhibition of angiogenesis. The purpose of this study was to investigate the association between expression of CXCR3 on peripheral blood leukocytes and Age-related Wet Macular Degeneration (AMD). Furthermore, we measured the plasma...

  7. Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

    Science.gov (United States)

    Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

  8. In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels

    DEFF Research Database (Denmark)

    Subhi, Yousif; Singh, Amardeep; Falk, Mads Krüger

    2014-01-01

    Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated...

  9. Real-world visual outcomes in patients with neovascular age-related macular degeneration receiving aflibercept at fixed intervals as per UK licence.

    Science.gov (United States)

    Ozturk, Mehmet; Harris, Martin L; Nguyen, Vuong; Barthelmes, Daniel; Gillies, Mark C; Mehta, Hemal

    2017-10-17

    To assess the impact of injection frequency on visual outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept. The UK licence for treatment of nAMD with aflibercept is based on the VIEW protocol. We tested the hypothesis that patients receiving fewer than the eight recommended injections in the first year would experience worse visual outcomes. Retrospective, single-centre observational study. There were 42 eyes from 42 patients included. Fight Retinal Blindness! software was used to record real-world outcomes of all treatment-naïve eyes receiving aflibercept for at least 1 year. Visual acuity (VA) at 1 year in eyes which received the recommended eight injections versus those receiving seven or fewer injections. There were 21 eyes (50%) that received the recommended eight aflibercept injections in the first year of treatment, whilst 14 eyes received seven injections, five received six injections and two received only five injections, with median VA change +7.0, +5.0, -4.0 and -6.5 LogMAR letters, respectively. Those eyes receiving seven or fewer injections had worse baseline vision. The main reasons for patients being undertreated were insufficient clinic capacity and non-attendance due to illness. Patients in the real-world receiving aflibercept for nAMD at fixed intervals as per UK licence could achieve similar visual improvement at 1 year compared with phase III clinical trials. Undertreated patients had worse visual outcomes. Measures need to be introduced to increase clinic capacity and closely follow non-attenders to improve future outcomes. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  10. The Relationship of Dietary ω-3 Long-Chain Polyunsaturated Fatty Acid Intake With Incident Age-Related Macular Degeneration AREDS Report No. 23

    Science.gov (United States)

    SanGiovanni, John Paul; Chew, Emily Y.; Agron, Elvira; Clemons, Traci E.; Ferris, Frederick L.; Gensler, Gary; Lindblad, Anne S.; Milton, Roy C.; Seddon, Johanna M.; Klein, Ronald; Sperduto, Robert D.

    2009-01-01

    Objective To examine the association of dietary ω-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). Methods Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures. Results After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. Conclusions Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary ω-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA. PMID:18779490

  11. Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth G Holliday

    Full Text Available Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD. While genome-wide association studies (GWAS for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH (peak P = 1.5×10(-31 and age-related maculopathy susceptibility 2 (ARMS2 (P = 4.3×10(-24 loci, and suggested Apolipoprotein E (ApoE polymorphisms (rs2075650; P = 1.1×10(-6 associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10(-6 and upstream of GLI2 (rs6721654; P = 6.5×10(-6, encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR gene (rs621313; P = 3.5×10(-6, involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.

  12. Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

    Science.gov (United States)

    Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

    2016-01-01

    To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

  13. Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration

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    Klein Michael L

    2011-07-01

    Full Text Available Abstract Background Age related macular degeneration (AMD is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH, the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD. Methods Human peripheral blood mononuclear cells (PBMCs were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500. Results We show that C5a promotes interleukin (IL-22 and IL-17 expression by human CD4+ T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4+ cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls. Conclusions Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.

  14. Serum Paraoxonase activity in relation to lipid profile in Age-related Macular Degeneration patients.

    Science.gov (United States)

    AnandBabu, Kannadasan; Bharathidevi, S R; Sripriya, Sarangapani; Sen, Parveen; Prakash, Vadivelu Jaya; Bindu, Appukuttan; Viswanathan, Natarajan; Angayarkanni, Narayanasamy

    2016-11-01

    Age-related Macular Degeneration (AMD) is a multifactorial disease causing visual impairment in old age. Oxidative stress is one of the main contributors for the disease progression. Paraoxonase (PON), a HDL-resident antioxidant enzyme which removes oxidized low density lipoprotein (oxLDL), which is not studied much in AMD. This study assesses the PON activities in relation to the lipid status and genetic variants in AMD patients. In this prospective case-control study, a total of 48 AMD patients and 30 unrelated healthy controls were recruited. The serum oxLDL and Plasma Homocysteine (Hcy) levels were estimated by ELISA. Plasma Homocysteine thiolactone (HCTL) was estimated by HPLC. Serum PON activities were estimated by spectrophotometry. PON gene expression was assessed by qPCR and protein expression by western blot, immunofluorescence and FACS analysis. Two known single nucleotide polymorphisms (SNPs) in the coding region of PON1, Q192R and L55M variants were checked in the AMD patients and controls and their association with PON activity and lipid levels were determined. Serum paraoxonase (PONase) and thiolactonase (PON-HCTLase) activities were significantly elevated in AMD patients than in controls apart from elevated serum levels of total cholesterol (TC), triglycerides (TG), oxLDL. While serum LDL levels in AMD patients correlate positively with PON HCTLase activity, the serum high density lipoprotein (HDL) correlates with both PONase and PON-HCTLase activities. However, multiple regression analysis showed that, amongst the parameters, only serum TG was a significant risk factor for AMD, after adjusting for demographic parameters as well as cataract. PON2 was significantly increased at the level of gene expression (p = 0.03) as seen in circulating peripheral blood mononuclear cells (PBMC) of AMD patients possibly mediated by the transcription factor SP1, that showed 2-fold increase. PON1 and 2 protein expressions also showed significant increase in the PBMC

  15. Mitochondrial variation and the risk of age-related macular degeneration across diverse populations.

    Science.gov (United States)

    Restrepo, Nicole A; Mitchell, Sabrina L; Goodloe, Robert J; Murdock, Deborah G; Haines, Jonanthan L; Crawford, Dana C

    2015-01-01

    Substantial progress has been made in identifying susceptibility variants for age-related macular degeneration (AMD). The majority of research to identify genetic variants associated with AMD has focused on nuclear genetic variation. While there is some evidence that mitochondrial genetic variation contributes to AMD susceptibility, to date, these studies have been limited to populations of European descent resulting in a lack of data in diverse populations. A major goal of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study is to describe the underlying genetic architecture of common, complex diseases across diverse populations. This present study sought to determine if mitochondrial genetic variation influences risk of AMD across diverse populations. We performed a genetic association study to investigate the contribution of mitochondrial DNA variation to AMD risk. We accessed samples from the National Health and Nutrition Examination Surveys, a U.S population-based, cross-sectional survey collected without regard to health status. AMD cases and controls were selected from the Third NHANES and NHANES 2007-2008 datasets which include non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. AMD cases were defined as those > 60 years of age with early/late AMD, as determined by fundus photography. Targeted genotyping was performed for 63 mitochondrial SNPs and participants were then classified into mitochondrial haplogroups. We used logistic regression assuming a dominant genetic model adjusting for age, sex, body mass index, and smoking status (ever vs. never). Regressions and meta-analyses were performed for individual SNPs and mitochondrial haplogroups J, T, and U. We identified five SNPs associated with AMD in Mexican Americans at p < 0.05, including three located in the control region (mt16111, mt16362, and mt16319), one in MT-RNR2 (mt1736), and one in MT-ND4 (mt12007). No mitochondrial variant or haplogroup was significantly

  16. Transpupillary thermotherapy for choroidal neovascular membrane in age related macular degeneration

    Directory of Open Access Journals (Sweden)

    Agarwal Manisha

    2004-01-01

    Full Text Available Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT in choroidal neovasularisation (CNVM secondary to age related macular degeneration ( AMD. Material and methods: Retrospective, non-randomized study of 28 eyes of 28 patients with subfoveal CNVM (classic, occult or mixed secondary to AMD. Results: Fifteen patients (53.57% maintained their pre-treatment vision, 2 (7.14% patients showed improvement of more than 2 lines and 11(39.28% patients showed deterioration of vision by> 2 lines. Angiographic and clinical regression of CNVM was noted in 19 patients (67.8% on an average follow up of 15.32 ± 3.31 months. Conclusion: TTT leads to stabilisation of vision in 60% of treated eyes with CNVM due to AMD.

  17. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Zhenglin Yang

    2010-02-01

    Full Text Available A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

  18. COL8A1 rs13095226 polymorphism shows no association with neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in Chinese subjects.

    Science.gov (United States)

    Yu, Yang; Huang, Lvzhen; Wang, Bin; Zhang, Chunfang; Bai, Yujing; Li, Xiaoxin

    2015-01-01

    Age-related macular degeneration (AMD) is the main cause of visual impairment and legal blindness in older individuals. COL8A1 rs13095226 variants have recently been implicated associated with neovascular age-related macular degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV) in American studies. The aim of this study was to investigate the association between the COL8A1 rs13095226 Polymorphism and neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese people. 900 Chinese subjects-300 cases with nAMD, 300 cases with PCV and 300 controls, were enrolled in a cross-sectional observational study. The diagnoses of nAMD and PCV were confirmed by Fundus photography, Fluorescence Fundus Angiography (FFA) and Indocyanine Green Angiography (ICGA). Genomic DNA was extracted from venous blood leukocytes and genotypes of rs13095226 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Differences in allele distribution between cases and controls were tested by chi-square tests, with age and gender adjusted by logistic regression analysis. The COL8A1 rs13095226 polymorphism was not statistically significantly different from the nAMD or PCV to the normal controls (P>0.05) in Chinese Population. The association remained insignificant after adjustment for age and gender differences (P>0.05). This case-control study indicated that the COL8A1 rs13095226 polymorphism is not associated with nAMD or PCV, which suggesting this gene maybe not a susceptibility gene locus for nAMD or PCV in Chinese subjects.

  19. Refractive error and risk of early or late age-related macular degeneration: a systematic review and meta-analysis.

    Science.gov (United States)

    Li, Ying; Wang, Jiwen; Zhong, Xiaojing; Tian, Zhen; Wu, Peipei; Zhao, Wenbo; Jin, Chenjin

    2014-01-01

    To summarize relevant evidence investigating the associations between refractive error and age-related macular degeneration (AMD). Systematic review and meta-analysis. We searched Medline, Web of Science, and Cochrane databases as well as the reference lists of retrieved articles to identify studies that met the inclusion criteria. Extracted data were combined using a random-effects meta-analysis. Studies that were pertinent to our topic but did not meet the criteria for quantitative analysis were reported in a systematic review instead. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between refractive error (hyperopia, myopia, per-diopter increase in spherical equivalent [SE] toward hyperopia, per-millimeter increase in axial length [AL]) and AMD (early and late, prevalent and incident). Fourteen studies comprising over 5800 patients were eligible. Significant associations were found between hyperopia, myopia, per-diopter increase in SE, per-millimeter increase in AL, and prevalent early AMD. The pooled ORs and 95% CIs were 1.13 (1.06-1.20), 0.75 (0.56-0.94), 1.10 (1.07-1.14), and 0.79 (0.73-0.85), respectively. The per-diopter increase in SE was also significantly associated with early AMD incidence (OR, 1.06; 95% CI, 1.02-1.10). However, no significant association was found between hyperopia or myopia and early AMD incidence. Furthermore, neither prevalent nor incident late AMD was associated with refractive error. Considerable heterogeneity was found among studies investigating the association between myopia and prevalent early AMD (P = 0.001, I2 = 72.2%). Geographic location might play a role; the heterogeneity became non-significant after stratifying these studies into Asian and non-Asian subgroups. Refractive error is associated with early AMD but not with late AMD. More large-scale longitudinal studies are needed to further investigate such associations.

  20. Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

    Science.gov (United States)

    Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

    2017-01-01

    To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. Cross-sectional, population-based epidemiologic study. Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women. Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design. Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA). Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds compared with those in

  1. Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Erin W. [Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI (United States); Schaumberg, Debra A. [Division of Preventive Medicine, Brigham and Women' s Hospital, Harvard Medical School and Department of Epidemiology, Harvard School of Public Health, Boston, MA (United States); Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT (United States); Park, Sung Kyun, E-mail: sungkyun@umich.edu [Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI (United States); Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI (United States)

    2014-08-15

    Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age

  2. IL-33 amplifies an innate immune response in the degenerating retina

    Science.gov (United States)

    Xi, Hongkang; Katschke, Kenneth J.; Li, Yun; Truong, Tom; Lee, Wyne P.; Diehl, Lauri; Rangell, Linda; Tao, Jianhua; Arceo, Rommel; Eastham-Anderson, Jeffrey; Hackney, Jason A.; Iglesias, Antonio; Cote-Sierra, Javier; Elstrott, Justin; Weimer, Robby M.

    2016-01-01

    Age-related macular degeneration (AMD), a leading cause of vision impairment in the ageing population, is characterized by irreversible loss of retinal pigment epithelial (RPE) cells and photoreceptors and can be associated with choroidal neovascularization. Mononuclear phagocytes are often present in AMD lesions, but the processes that direct myeloid cell recruitment remain unclear. Here, we identify IL-33 as a key regulator of inflammation and photoreceptor degeneration after retina stress or injury. IL-33+ Müller cells were more abundant and IL-33 cytokine was elevated in advanced AMD cases compared with age-matched controls with no AMD. In rodents, retina stress resulted in release of bioactive IL-33 that in turn increased inflammatory chemokine and cytokine expression in activated Müller cells. Deletion of ST2, the IL-33 receptor α chain, or treatment with a soluble IL-33 decoy receptor significantly reduced release of inflammatory mediators from Müller cells, inhibited accumulation of mononuclear phagocytes in the outer retina, and protected photoreceptor rods and cones after a retina insult. This study demonstrates a central role for IL-33 in regulating mononuclear phagocyte recruitment to the photoreceptor layer and positions IL-33 signaling as a potential therapeutic target in macular degenerative diseases. PMID:26755704

  3. Serological association of Chlamydia pneumoniae infection with age-related macular degeneration: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xueyu Chen

    Full Text Available We investigated the serological association of Chlamydia pneumoniae infection with age-related macular degeneration (AMD.A systematic review and meta-analysis was performed. PubMed, Embase, Web of Science and the Association of Research in Vision and Ophthalmology abstracts were searched to identify studies investigating the serological association of Chlamydia pneumoniae infection with age-related macular degeneration. The quality of original studies was assessed using the Newcastle-Ottawa scale. Heterogeneity was explored with meta-regression. The odds ratios (ORs and standardized mean differences (SMD of Chlamydia pneumoniae infection between AMD patients and controls were pooled.In total, 9 studies met the inclusion criteria using the Newcastle-Ottawa scale scores ranging from 4 to 9. There was heterogeneity among studies due to a difference in the study designs and measurement of exposure to Chlamydia pneumoniae infection. The overall OR of Chlamydia pneumoniae infection with AMD was 1.11 (95% confidence interval: 0.78-1.57, P = 0.56. The overall SMD of antibody titer between AMD and control was 0.43 (95% confidence interval: -0.12 to 0.99, P = 0.13.Evidence from the current published literature suggested no statistically significant association between Chlamydia pneumoniae infection and AMD.

  4. Serological association of Chlamydia pneumoniae infection with age-related macular degeneration: a systematic review and meta-analysis.

    Science.gov (United States)

    Chen, Xueyu; Jhanji, Vishal; Chen, Chupeng; Chen, Haoyu

    2014-01-01

    We investigated the serological association of Chlamydia pneumoniae infection with age-related macular degeneration (AMD). A systematic review and meta-analysis was performed. PubMed, Embase, Web of Science and the Association of Research in Vision and Ophthalmology abstracts were searched to identify studies investigating the serological association of Chlamydia pneumoniae infection with age-related macular degeneration. The quality of original studies was assessed using the Newcastle-Ottawa scale. Heterogeneity was explored with meta-regression. The odds ratios (ORs) and standardized mean differences (SMD) of Chlamydia pneumoniae infection between AMD patients and controls were pooled. In total, 9 studies met the inclusion criteria using the Newcastle-Ottawa scale scores ranging from 4 to 9. There was heterogeneity among studies due to a difference in the study designs and measurement of exposure to Chlamydia pneumoniae infection. The overall OR of Chlamydia pneumoniae infection with AMD was 1.11 (95% confidence interval: 0.78-1.57, P = 0.56). The overall SMD of antibody titer between AMD and control was 0.43 (95% confidence interval: -0.12 to 0.99, P = 0.13). Evidence from the current published literature suggested no statistically significant association between Chlamydia pneumoniae infection and AMD.

  5. What is new in the management of wet age-related macular degeneration?

    Science.gov (United States)

    Sivaprasad, Sobha; Hykin, Philip

    2013-01-01

    The hallmark of wet age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The key cytokine involved in the pathogenesis of CNV is vascular endothelial growth factor (VEGF). Since 2005, antiVEGF therapy has revolutionized the management of this condition. A systematic computerized literature search was conducted on PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). AntiVEGF therapy has resulted in improvement in visual function and performance. Currently, practitioners are spoilt for choice of these agents. Bevacizumab is unlicensed for intraocular use but has a better market share than ranibizumab in the treatment of wet AMD as it is approximately 40 times cheaper than ranibizumab, if aliquoted into smaller doses for intraocular use. This has stirred up questions on indemnity, safety, dosing, treatment regimen and quality control, despite the fact that well-designed clinical trials have shown that both drugs are equally effective. Another dilemma for the physicians is the choice of treatment regimens with antiVEGF agents that include fixed dosing, optical coherence tomography (OCT)-guided re-treatment, treat and extend or a combination of proactive and reactive dosing. Real-life outcomes of physician-dependent OCT-guided re-treatment with these agents are inferior to outcomes reported in clinical trials. A recently food and drug administration-approved antiVEGF agent, aflibercept, is rapidly becoming a popular choice as well-designed randomized clinical trials indicate that eight weekly fixed dosing of aflibercept is non-inferior to monthly ranibizumab. Options for reducing the frequency of repeated intravitreal injections are being explored. Combination therapy with photodynamic therapy and epimacular brachytherapy seem scientifically plausible due to their synergistic effects. However, so far the results on these combinations have not shown any superior visual outcomes to antiVEGF monotherapy, and the practicalities of delivering these

  6. Reading Speed and Reading Comprehension in Age-related Macular Degeneration.

    Science.gov (United States)

    Varadaraj, Varshini; Lesche, Stephen; Ramulu, Pradeep Y; Swenor, Bonnielin K

    2018-02-01

    To evaluate the impact of age-related macular degeneration (AMD) on short out-loud and sustained silent reading speeds, and reading comprehension. Prospective, cross-sectional. Setting: Wilmer Eye Institute. Literate, native-English speakers with and without AMD. AMD participants had better-eye visual acuity (VA) 20/100, while controls had binocular VA >20/32. MNRead was used to assess short-duration out-loud reading speed. Sustained silent reading test was used to evaluate sustained silent reading speeds, while reading comprehension was assessed based on silent reading test text. MNRead maximum reading speed, sustained-silent reading speed, and comprehension score. Analyses included 24 AMD patients and 22 controls. In age-adjusted regressions, AMD participants, compared to controls, read 46 words per minute (wpm) slower on MNRead (95% confidence interval [CI]: -66, -26, P reading speeds between groups (β = 0.99, 95% CI: -41.8, 43.8, P = .96). In other models, there was a decrement of 12.6 wpm on MNRead per 0.1 worsening logMAR (95% CI: -18.7, -6.6, P reading speed (β = -10.1, 95% CI: -22.4, 2.1, P = .10). However, AMD participants had substantially lower comprehension scores than controls (53% vs 85% correct, P read slower than controls when forced to read out loud. When asked to read silently over a longer duration, both groups read at similar speeds, though AMD patients demonstrated substantially lower comprehension scores, suggesting that they chose to sacrifice comprehension for speed. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

    Science.gov (United States)

    Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

    2018-02-01

    Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

  8. Ex Vivo Confocal Spectroscopy of Autofluorescence in Age-Related Macular Degeneration.

    Directory of Open Access Journals (Sweden)

    Joel Kaluzny

    Full Text Available We investigated the autofluorescence (AF signature of the microscopic features of retina with age-related macular degeneration (AMD using 488 nm excitation.The globes of four donors with AMD and four age-matched controls were embedded in paraffin and sectioned through the macula. Sections were excited using a 488 nm argon laser, and the AF emission was captured using a laser scanning confocal microscope (496-610 nm, 6 nm resolution. The data cubes were then analyzed to compare peak emission spectra between the AMD and the controls. Microscopic features, including individual lipofuscin and melanolipofuscin granules, Bruch's Membrane, as well macroscopic features, were considered.Overall, the AMD eyes showed a trend of blue-shifted emission peaks compared with the controls. These differences were statistically significant when considering the emission of the combined RPE/Bruch's Membrane across all the tissue cross-sections (p = 0.02.The AF signatures of ex vivo AMD RPE/BrM show blue-shifted emission spectra (488 nm excitation compared with the control tissue. The magnitude of these differences is small (~4 nm and highlights the potential challenges of detecting these subtle spectral differences in vivo.

  9. Small Drusen and Age-Related Macular Degeneration: The Beaver Dam Eye Study

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    Ronald Klein

    2015-03-01

    Full Text Available We tested the hypothesis that large areas of small hard drusen (diameter <63 µm and intermediate drusen (diameter 63–124 µm are associated with the incidence of age-related macular degeneration (AMD. Eyes of 3344 older adults with at least two consecutive visits spaced five years apart over a 20-year period were included. A 6-level severity scale, including no drusen, four levels of increasing area (from minimal (<2596 µm² to large (>9086 µm² of only small hard drusen, and intermediate drusen, was used. The five-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR of developing AMD in eyes with a large area of only small drusen was 1.8 (p < 0.001. Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (p < 0.001 of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.

  10. Prevalence of age-related macular degeneration in old persons: Age, Gene/environment Susceptibility Reykjavik Study.

    Science.gov (United States)

    Jonasson, Fridbert; Arnarsson, Arsaell; Eiríksdottir, Gudny; Harris, Tamara B; Launer, Lenore J; Meuer, Stacy M; Klein, Barbara E; Klein, Ronald; Gudnason, Vilmundur; Cotch, Mary Frances

    2011-05-01

    To describe the prevalence and signs of early and late age-related macular degeneration (AMD) in an old cohort. Population-based cohort study. We included 5272 persons aged ≥66 years, randomly sampled from the Reykjavik area. Fundus images were taken through dilated pupils using a 45-degree digital camera and graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy (GA) using the modified Wisconsin Age-Related Maculopathy Grading System. Age-related macular degeneration in an elderly cohort. The mean age of participants was 76 years. The prevalence of early AMD was 12.4% (95% confidence interval [CI], 11.0-13.9) for those aged 66 to 74 years and 36% (95% CI, 30.9-41.1) for those aged ≥85 years. The prevalence of exudative AMD was 3.3% (95% CI, 2.8-3.8). The prevalence of pure GA was 2.4% (95% CI, 2.0-2.8). The highest prevalence of late AMD was among those aged ≥85 years: 11.4% (95% CI, 8.2-14.5) for exudative AMD and 7.6% (95% CI, 4.8-10.4) for pure GA. Persons aged ≥85 years have a 10-fold higher prevalence of late AMD than those aged 70 to 74 years. The high prevalence of late AMD in the oldest age group and expected increase of elderly people in the western world in coming years call for improved preventive measures and novel treatments. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  11. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

    Science.gov (United States)

    Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

    2017-07-01

    To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

  12. Implementation studies of ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Bloch, Sara Brandi

    2013-11-01

    comparing our results with other pro re nata regimens based on a monthly reassessment of disease activity that our patients could gain substantial vision if we optimized our frequency of re-examinations. The analysis demonstrated that we could discontinue treatment in patients who had a poor visual acuity during the first 3 months of treatment and that visual outcome could be improved by minimizing the delay from diagnosis of neovascular AMD to first administered ranibizumab injection. This study led to changes in departmental treatment procedures. In the second study, we found that type 2 CNV lesions had a higher hazard ratio as compared to type 1 CNV lesions in developing subfoveal fibrosis. Prominent subfoveal fibrous tissue and fibrous tissue with retinal atrophy led to poorer visual performances in eyes with neovascular AMD after 2 years of treatment as compared with eyes without subfoveal fibrous tissue. In the development of randomized clinical trials designed to address how treatment with VEGF inhibitors can be improved by limiting the growth of subfoveal fibrous tissue or neuroretinal atrophy, it is important to define subgroups of eyes at risk of these pathological changes. The second PhD study has contributed to identify this subgroup of eyes. The third study included in this PhD thesis revealed that the annual incidence rate of AMD-related legally blind persons registered in Denmark has halved during the last decade, with the bulk of the reduction observed after the introduction of ranibizumab for neovascular AMD.

  13. Smoking,serum antioxidant vitamin levels and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Sezen Akkaya Çakir

    2014-05-01

    Full Text Available AIM: To evaluate associations between the grades of age related macular degeneration(AMDand serum levels of antioxidant vitamins(vitamin A, C and Eand smoking. METHODS: Fifty-three AMD patients and 31 individuals having ages matching with the patient group were enrolled the study. Colored fundus photographs of the macula were used to place participants(n=84into one of the five groups(Grade I-Vbased on the frequency and severity of the lesions associated with AMD. Serum antioxidant vitamin levels were measured using High Performance Liquid Chromatography(HPLC. Smoking status was classified as non-smoker, ex-smoker and current smoker. Total number of packs smoked per year, was defined.RESULTS: The distribution of vitamin A, E, and C levels were 0.874±0.326mg/L, 10.739±4.874mg/L, 1.737±0.447mg/L in control group and 0.880±0.305mg/L, 9.487±6.060mg/L, 1.870±2.191mg/L in AMD group, respectively. The difference between AMD and control group was not statistically significant for vitamin A, E and C levels(P>0.05. There were no significant differences between subgroups of AMD for vitamin A(P=0.881and vitamin E(P=0.293but there was a contradicting rise of vitamin C levels(P=0.044with increasing levels of the disease. There were no significant differences between AMD and control group regarding smoking status, but there was a significant difference for total number of packs smoked per year(P=0.02. An increase of number of total packs smoked per year was determined along with the rising grade of AMD(P=0.007. CONCLUSION: We found no relation between AMD and serum levels of vitamin A and E but vitamin C levels was increase with AMD grades unexpectedly. We found dose-response relationship between smoking and AMD.

  14. A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

    Science.gov (United States)

    Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

    2016-05-01

    The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

  15. Association between neovascular age-related macular degeneration and dementia: a population-based case-control study in Taiwan.

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    Shiu-Dong Chung

    Full Text Available Most available studies focusing on the association between neovascular age-related macular degeneration (AMD and dementia have conflicting results. This study aimed to investigate the association between previously diagnosed AMD and dementia using a population-based dataset in Taiwan.Data for this case-control study were retrospectively collected from the Taiwan National Health Insurance Research Database. We identified 13,402 subjects who had a diagnosis of dementia as cases, and 40,206 subjects without dementia as controls. A conditional logistic regression was used to examine the association of dementia with previously diagnosed neovascular AMD.We found that of the study sample of 53,608 subjects, 1.01% had previously diagnosed neovascular AMD, 1.35% and 0.90% for cases and the controls, respectively (p<0.001. The conditional logistic regression analysis suggested that the odds ratio of prior neovascular AMD for cases was 1.37 (95% confidence interval: 1.14~1.65 compared to the controls after adjusting for subjects' age, monthly income, geographic location, urbanization level, and hyperlipidemia, diabetes, hypertension, stroke, ischemic heart disease, and whether or not a subjects underwent cataract surgery prior to index date than controls.Dementia subjects were associated with a higher proportion of prior neovascular AMD than were the controls.

  16. Leukocyte telomere length is associated with advanced age-related macular degeneration in the Han Chinese population.

    Science.gov (United States)

    Weng, Xiaoling; Zhang, Hong; Kan, Mengyuan; Ye, Junyi; Liu, Fatao; Wang, Ting; Deng, Jiaying; Tan, Yanfang; He, Lin; Liu, Yun

    2015-09-01

    Telomeres located at the ends of chromosomes are involved in genomic stability and play a key role in various cancers and age-related diseases. Age-related macular degeneration (AMD) is a late-onset, age-associated progressive neurodegenerative disease, which includes the geographic atrophy (GA) subtype and the choroidal neovascularization (CNV) subtype. To better understand how leukocyte telomere length (LTL) is related to AMD, we conducted an association study in 197 AMD patients and 259 healthy controls using the established quantitative PCR technique. Logistic regression was performed to evaluate the association of LTL and AMD with the age-adjusted ratio of the telomere length to the copy number of a single-copy gene (T/S). Notably, we found a significant association between AMD and LTL (OR=2.24; 95% CI=1.68-3.07; P=0.0001) after adjusting for age and sex. Furthermore, the results showed a strongly significant association between the GA subtype and the LTL (OR=4.81; 95% CI=3.15-7.82; P=0.0001) after adjusting for age and sex. Our findings provide evidence of the role that LTL plays in the pathological mechanisms of AMD, mainly in the GA subgroup but not the CNV subgroup. Copyright © 2015. Published by Elsevier Inc.

  17. Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch’s membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease.

  18. The Revival of a Failed Constructed Wetland Treating of a High Fe Load AMD

    Science.gov (United States)

    A.D. Karathanasis; C.D. Barton

    1999-01-01

    Acid mine drainage (AMD) from abandoned mines has significantly impaired water quality in eastern Kentucky. A small surface flow wetland constructed in 1989 to reduce AMD effects and subsequently failed after six months of operation was renovated by incorporating anoxic limestone drains (ALDs) and anaerobic subsurface drains promoting vertical flow through successive...

  19. It's not all about acid mine drainage (AMD) on the West Rand - there is dust too

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2012-08-01

    Full Text Available The West Rand is part of the Gauteng Province and is surrounded by mining activities. There have been several media and scientific reports about acid mine drainage (AMD) in this area. However, AMD is not the only environmental problem faced...

  20. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    OpenAIRE

    K. A. Mirzabekova

    2015-01-01

    Common pathogenic aspects of age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma wi...

  1. Optical Coherence Tomography Updates on Clinical and Technical Developments. Age-Related Macular Degeneration: Drusen and Geographic Atrophy

    Science.gov (United States)

    Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Holz, Frank G.

    Age-related macular degeneration (AMD) is a complex disease with both genetic and environmental factors influencing its development. With the advent of high-resolution OCT imaging, the characterization of drusen in AMD has become possible. The in vivo morphologic characteristics imaged with SD-OCT may represent distinct subclasses of drusen variants, may relate closely to ultrastructural drusen elements identified in donor eyes, and may be useful imaging biomarkers for disease severity or risk of progression [Khanifar et al. Ophthalmology 115(11):1883-1890, 2008].

  2. Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; la Cour, Morten; Sander, Birgit

    2013-01-01

    Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria...... and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4-week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best-corrected visual acuity (BCVA...

  3. Analysis OpenMP performance of AMD and Intel architecture for breaking waves simulation using MPS

    Science.gov (United States)

    Alamsyah, M. N. A.; Utomo, A.; Gunawan, P. H.

    2018-03-01

    Simulation of breaking waves by using Navier-Stokes equation via moving particle semi-implicit method (MPS) over close domain is given. The results show the parallel computing on multicore architecture using OpenMP platform can reduce the computational time almost half of the serial time. Here, the comparison using two computer architectures (AMD and Intel) are performed. The results using Intel architecture is shown better than AMD architecture in CPU time. However, in efficiency, the computer with AMD architecture gives slightly higher than the Intel. For the simulation by 1512 number of particles, the CPU time using Intel and AMD are 12662.47 and 28282.30 respectively. Moreover, the efficiency using similar number of particles, AMD obtains 50.09 % and Intel up to 49.42 %.

  4. Degenerate Euler zeta function

    OpenAIRE

    Kim, Taekyun

    2015-01-01

    Recently, T. Kim considered Euler zeta function which interpolates Euler polynomials at negative integer (see [3]). In this paper, we study degenerate Euler zeta function which is holomorphic function on complex s-plane associated with degenerate Euler polynomials at negative integers.

  5. Activating the AKT2-nuclear factor-κB-lipocalin-2 axis elicits an inflammatory response in age-related macular degeneration.

    Science.gov (United States)

    Ghosh, Sayan; Shang, Peng; Yazdankhah, Meysam; Bhutto, Imran; Hose, Stacey; Montezuma, Sandra R; Luo, Tianqi; Chattopadhyay, Sreya; Qian, Jiang; Lutty, Gerard A; Ferrington, Deborah A; Zigler, J Samuel; Sinha, Debasish

    2017-04-01

    Age-related macular degeneration (AMD) is a complex and progressive degenerative eye disease resulting in severe loss of central vision. Recent evidence indicates that immune system dysregulation could contribute to the development of AMD. We hypothesize that defective lysosome-mediated clearance causes accumulation of waste products in the retinal pigmented epithelium (RPE), activating the immune system and leading to retinal tissue injury and AMD. We have generated unique genetically engineered mice in which lysosome-mediated clearance (both by phagocytosis and autophagy) in RPE cells is compromised, causing the development of features of early AMD. Our recent data indicate a link between lipocalin-2 (LCN-2) and the inflammatory responses induced in this mouse model. We show that nuclear factor-κB (NF-κB) and STAT-1 may function as a complex in our animal model system, together controlling the upregulation of LCN-2 expression in the retina and stimulating an inflammatory response. This study revealed increased infiltration of LCN-2-positive neutrophils in the choroid and retina of early AMD patients as compared with age-matched controls. Our results demonstrate that, both in our animal model and in human AMD, the AKT2-NF-κB-LCN-2 signalling axis is involved in activating the inflammatory response, making this pathway a potential target for AMD treatment. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Anxiety and depression in patients with advanced macular degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Cimarolli VR

    2015-12-01

    Full Text Available Verena R Cimarolli,1 Robin J Casten,2 Barry W Rovner,3–5 Vera Heyl,6 Silvia Sörensen,7,8 Amy Horowitz9 1Research Institute on Aging, Jewish Home Lifecare, New York, NY, USA; 2Department of Psychiatry and Human Behavior, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 3Department of Neurology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 4Department of Psychiatry, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 5Department of Ophthalmology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 6Institute of Special Education, University of Education, Heidelberg, Germany; 7Warner School of Education and Human Development, University of Rochester, Rochester, NY, USA; 8Department of Ophthalmology, Flaum Eye Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 9Graduate School of Social Service, Fordham University, New York, NY, USA Abstract: Age-related macular degeneration (AMD – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to

  7. Risk of macular degeneration affected by polymorphisms in Matrix metalloproteinase-2: A case-control study in Chinese Han population.

    Science.gov (United States)

    Cheng, Jie; Hao, Xiaolin; Zhang, Zhongchen

    2017-11-01

    The purpose of this study was to investigate the correlation of single nucleotide polymorphisms (SNPs) in Matrix metalloproteinase -2 (MMP-2) gene and the risk of age-related macular degeneration (AMD) in Chinese Han population.A total of 126 AMD patients and 141 healthy controls participated in this study. Genotypes of MMP-2 gene polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). χtest was used to detect the differences of genotypes and alleles frequencies between case and control groups. Relative risk of AMD was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs).Distribution of variant allele carriers (computed tomography + TT genotypes) of MMP-2 gene rs243865 SNP was significantly different between case and control groups, and might act as protective factors for the onset of AMD (P = .044, OR = 0.583, 95% CI = 0.344-0.987). Nevertheless, the T allele might reduce the AMD risk (P = .030, OR = 0.611, 95% CI = 0.390-0.956). However, no significant association existed between rs243865 and AMD risk in the subgroup analysis based on age. GA + AA genotypes of rs243866 SNP may associate with a decreased risk of AMD in the age≤65 years subgroup (P = .028, OR = 0.399, 95% CI = 0.174-0.915).MMP-2 gene rs243865 and rs243866 SNPs associated with the risk of AMD. Further studies should be performed to confirm the results. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  8. Metallothionein polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration.

    Science.gov (United States)

    García, Montserrat; Álvarez, Lydia; Fernández, Ángela; González-Iglesias, Héctor; Escribano, Julio; Fernández-Vega, Beatriz; Villota, Eva; Fernández-Vega Cueto, Luis; Fernández-Vega, Álvaro; Coca-Prados, Miguel

    2017-01-01

    To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD). A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case-control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software. The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10 -4 ; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11-41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71-0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed. The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.

  9. Association of HDL-related loci with age-related macular degeneration and plasma lutein and zeaxanthin: the Alienor study.

    Directory of Open Access Journals (Sweden)

    Bénédicte M J Merle

    Full Text Available BACKGROUND: Several genes implicated in high-density lipoprotein (HDL metabolism have been reported to be associated with age-related macular degeneration (AMD. Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations. METHODS: Alienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC, rs3764261 (CETP, rs12678919 (LPL and rs1883025 (ABCA1. RESULTS: After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively, and with higher plasma zeaxanthin concentrations (p=0.03, while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05 and both with plasma lipids and plasma lutein (p=0.047. Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance. CONCLUSION: These findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.

  10. The 'Displacing Foods of Modern Commerce' Are the Primary and Proximate Cause of Age-Related Macular Degeneration: A Unifying Singular Hypothesis.

    Science.gov (United States)

    Knobbe, Chris A; Stojanoska, Marija

    2017-11-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness in developed nations. AMD is anticipated to affect 196 million people worldwide, by 2020. However, the etiology of this disease remains unknown. Aging, genetic, and environmental influences have generally been implicated as major etiologic factors. We sought to examine the hypothesis that consumption of the 'displacing foods of modern commerce,' which equate to processed, nutrient-deficient and potentially toxic foods, may be the primary and proximate cause of AMD. To evaluate this hypothesis, we ran correlative AMD prevalence data against well-known proxy markers of processed food consumption, namely, sugar and vegetable oils, in 25 nations. In twenty-one nations, published studies provided AMD prevalence data and in four Pacific Island nations, practicing ophthalmologists in the regions completed retrospective chart analyses to estimate AMD prevalence in their respective regions. To estimate AMD prevalence historically, an extensive review of published papers and ophthalmic literature was completed. This review indicates that, between the years 1851 and 1930, AMD was a medical rarity worldwide, which then rose modestly in prevalence in the 1930s in the U.S. and U.K, finally elevating to epidemic proportions by 1975 in the U.S. Numerous developed nations have followed suit in recent decades. Simultaneously, between approximately 1880 and 2009, processed, nutrient-deficient foods gradually supplanted and displaced whole, unprocessed, nutrient-dense foods in developed nations, such that by 2009, 63 percent of the American diet was made up of nutrient-deficient foods in the form of refined white flour, added sugars, vegetable oils, and artificially created trans fats. The correlative data in 25 nations shows that increasing sugar and polyunsaturated vegetable oil consumption is invariably associated with new onset or rising prevalence of AMD, generally within about

  11. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration

    Science.gov (United States)

    Virgili, Gianni; Michelessi, Manuele; Parodi, Maurizio B; Bacherini, Daniela; Evans, Jennifer R

    2016-01-01

    Background Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye. It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss. Objectives To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Selection criteria Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group. Data collection and analysis Two review authors independently

  12. Patient-reported utilities in bilateral visual impairment from amblyopia and age-related macular degeneration.

    Science.gov (United States)

    van de Graaf, Elizabeth S; Despriet, Dominiek D G; Klaver, Caroline C W; Simonsz, Huibert J

    2016-05-17

    Utility of visual impairment caused by amblyopia is important for the cost-effectiveness of screening for amblyopia (lazy eye, prevalence 3-3.5 %). We previously measured decrease of utility in 35-year-old persons with unilateral persistent amblyopia. The current observational case-control study aimed to measure loss of utility in patients with amblyopia with recent decrease of vision in their better eye. As these patients are rare, the sample was supplemented by patients with bilateral age-related macular degeneration with similar decrease of vision. From our out-patient department, two groups of patients with recent deterioration to bilateral visual acuity less than Snellen 0.5 (bilateral visual impairment, BVI) were recruited, with either persistent amblyopia and age-related macular degeneration (AMB + AMD), or with bilateral age-related macular degeneration (BAMD). To measure utility, the time trade-off method and the standard gamble method were applied through interviews. Correlations were sought between utility values and visual acuity, age and Visual Function Questionnaire-25 scores. Seventeen AMB + AMD patients (mean age 72.9 years), and 63 BAMD patients (mean age 79.6 years) were included in the study. Among AMB + AMD, 80 % were willing to trade lifetime in exchange for cure. The overall mean time trade-off utility was 0.925. Among BAMD, 75 % were willing to trade, utility was 0.917. Among AMB + AMD, 38 % accepted risk of death in exchange for cure, overall mean standard gamble utility was 0.999. Among BAMD, 49 % accepted risk of death, utility was 0.998. Utility was not related to visual acuity but it was to age (p = 0.02). Elderly patients with BVI, caused by persistent amblyopia and age-related macular degeneration (AMD) or by bilateral AMD, had an approximately 8 % loss of TTO utility. Notably, the 8 % loss in elderly with BVI differs little from the 3.7 % loss we found previously in 35-year-old persons with unilateral

  13. Added value of OCT in evaluating the presence of leakage in patients with age-related macular degeneration treated with PDT

    NARCIS (Netherlands)

    van Velthoven, M. E. J.; de Smet, M. D.; Schlingemann, R. O.; Magnani, M.; Verbraak, F. D.

    2006-01-01

    BACKGROUND: Evaluating the presence of leakage on fluorescein angiography (FA) in patients with age-related macular degeneration (AMD) retreated with photodynamic therapy (PDT) can be difficult. New diagnostic tools such as optical coherence tomography (OCT) might help to optimize PDT management.

  14. Roles for the ubiquitin-proteasome pathway in protein quality control and signaling in the retina: implications in the pathogenesis of age-related macular degeneration

    Science.gov (United States)

    The accumulation of damaged or postsynthetically modified proteins and dysregulation of inflammatory responses and angiogenesis in the retina/RPE are thought be etiologically related to formation of drusen and choroidal neovascularization (CNV), hallmarks of age-related macular degeneration (AMD). T...

  15. Targeted Vision Function Goals and Use of Vision Resources in Ophthalmology Patients with Age-Related Macular Degeneration and Comorbid Depressive Symptoms

    Science.gov (United States)

    Casten, Robin; Rovner, Barry W.; Fontenot, Joseph L.

    2016-01-01

    Introduction: This study characterizes self-reported functional vision goals and the use of low vision resources (for example, services and devices) in ophthalmology clinic patients with age-related macular degeneration (AMD) and comorbid depressive symptoms. Methods: From July 2009 to February 2013, we assessed 188 consecutive patients (age 65+;…

  16. IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

    DEFF Research Database (Denmark)

    Ross, Christian; Engler, Claus Bødker; Sander, Birgit

    2002-01-01

    We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

  17. Joint Analysis of Nuclear and Mitochondrial Variants in Age-Related Macular Degeneration Identifies Novel Loci TRPM1 and ABHD2/RLBP1

    NARCIS (Netherlands)

    Persad, P.J.; Heid, I.M.; Weeks, D.E.; Baird, P.N.; Jong, E.K.; Haines, J.L.; Pericak-Vance, M.A.; Scott, W.K.

    2017-01-01

    Purpose: Presently, 52 independent nuclear single nucleotide polymorphisms (nSNPs) have been associated with age-related macular degeneration (AMD) but their effects do not explain all its variance. Genetic interactions between the nuclear and mitochondrial (mt) genome may unearth additional genetic

  18. Consuming a buttermilk drink containing lutein-enriched egg yolk daily for 1 year increased plasma lutein but did not affect serum lipid or lipoprotein concentrations in adults with early signs of age-related macular degeneration.

    Science.gov (United States)

    van der Made, Sanne M; Kelly, Elton R; Berendschot, Tos T J M; Kijlstra, Aize; Lütjohann, Dieter; Plat, Jogchum

    2014-09-01

    Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid and lipoprotein and plasma lutein concentrations. Additionally, subgroups that could potentially benefit the most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio upon consumption of the lutein-enriched egg yolk drink (P cholesterol upon consumption was significantly different between these 3 groups (P cholesterol absorbers particularly might benefit from the lutein-enriched buttermilk drink. This study was registered at clinicaltrials.gov as NCT00902408. © 2014 American Society for Nutrition.

  19. Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration

    Science.gov (United States)

    Moja, Lorenzo; Lucenteforte, Ersilia; Kwag, Koren H; Bertele, Vittorio; Campomori, Annalisa; Chakravarthy, Usha; D’Amico, Roberto; Dickersin, Kay; Kodjikian, Laurent; Lindsley, Kristina; Loke, Yoon; Maguire, Maureen; Martin, Daniel F; Mugelli, Alessandro; Mühlbauer, Bernd; Püntmann, Isabel; Reeves, Barnaby; Rogers, Chris; Schmucker, Christine; Subramanian, Manju L; Virgili, Gianni

    2014-01-01

    Background Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off-label to treat neovascular AMD. Objectives To assess the systemic safety of intravitreal bevacizumab (brand name Avastin®; Genentech/Roche) compared with intravitreal ranibizumab (brand name Lucentis®; Novartis/Genentech) in people with neovascular AMD. Primary outcomes were death and All serious systemic adverse events (All SSAEs), the latter as a composite outcome in accordance with the International Conference on Harmonisation Good Clinical Practice. Secondary outcomes examined specific SSAEs: fatal and non-fatal myocardial infarctions, strokes, arteriothrombotic events, serious infections, and events grouped in some Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC). We assessed the safety at the longest available follow-up to a maximum of two years. Search methods We searched CENTRAL, MEDLINE, EMBASE and other online databases up to 27 March 2014. We also searched abstracts and clinical study presentations at meetings, trial registries, and contacted authors of included studies when we had questions. Selection criteria Randomised controlled trials (RCTs) directly comparing intravitreal bevacizumab (1.25 mg) and ranibizumab (0.5 mg) in people with neovascular AMD, regardless of publication status, drug dose, treatment regimen, or follow-up length, and whether the SSAEs of interest were

  20. Perceptual learning in patients with macular degeneration

    Directory of Open Access Journals (Sweden)

    Tina ePlank

    2014-10-01

    Full Text Available Patients with age-related macular degeneration (AMD or hereditary macular dystrophies (JMD rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT at their preferred retinal locus (PRL used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later took part in three functional magnetic resonance imaging (fMRI sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p=.001 in the stimulus onset asynchrony (SOA between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p=.014. The following trends were observed: (i Improvement in Vernier acuity for an eccentric line-bisection task; (ii positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r=0.531; (iii positive correlation between the increase in task performance and initial fixation stability (r=0.730. The first two trends were non-significant, whereas the third trend was significant at p=.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

  1. Outer retinal tubulation as a predictor of the enlargement amount of geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Hariri, Amirhossein; Nittala, Muneeswar G; Sadda, SriniVas R

    2015-02-01

    To determine the prognostic value of outer retinal tubulation (ORT) in the enlargement amount of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Cohort study. One hundred eight fellow untreated eyes of 143 patients with GA resulting from AMD enrolled in the MAHALO study (clinicaltrials.gov identifier, NCT01229215) who completely satisfied the study term and had gradable spectral-domain optical coherence tomography (OCT) images obtained at both baseline and month 18 visits. The MAHALO study enrolled 143 subjects into a phase 1b/2 multicenter, randomized, single-masked, sham-injection controlled clinical trial of the safety, tolerability, and evidence of activity of lampalizumab in patients with GA associated with AMD. Spectral-domain optical coherence tomography images were obtained at multiple time points in both eyes, although only the baseline and month 18 data of the fellow (nonstudy) eyes were considered in this exploratory analysis. The Cirrus HD-OCT review software was used for automatic segmentation and measurement of GA areas, with manual correction of segmentation errors by certified OCT graders. Baseline OCT images also were assessed for the presence of ORT. The enlargement amount of GA in eyes with ORT was compared with that of eyes without ORT. Comparison of the enlargement amount of GA in eyes with and without ORT. Twenty-four of these 108 eyes demonstrated evidence of ORT. The amount of enlargement of GA in eyes with ORT was significantly slower than that of eyes without ORT (1.85±0.78 vs. 2.67±1.61; P = 0.001). This difference remained significant when considering subgroups with unifocal or multifocal GA lesions, because eyes with ORT in both subgroups had a slower enlargement amount of GA than eyes without ORT (2.91±1.70 vs. 2.08±0.88 [P = 0.01], in eyes with multifocal GA lesions; and 2.24±1.40 vs. 1.63±0.57 [P = 0.02], in eyes with unifocal GA lesions). In eyes with ORT, GA lesions seem to enlarge at a

  2. Macular Degeneration Prevention and Risk Factors

    Science.gov (United States)

    ... of adults over 75 are affected by AMD. Smoking Smoking increases a person’s chances of developing AMD ... Research Program National Glaucoma Research Program Molecular Neurodegeneration Journal Grants Types of Grants Deadlines & Guidelines Apply for ...

  3. Interaction of complement factor h and fibulin3 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    M Keith Wyatt

    Full Text Available Age-related macular degeneration (AMD is a major cause of vision loss. It is associated with development of characteristic plaque-like deposits (soft drusen in Bruch's membrane basal to the retinal pigment epithelium (RPE. A sequence variant (Y402H in short consensus repeat domain 7 (SCR7 of complement factor H (CFH is associated with risk for "dry" AMD. We asked whether the eye-targeting of this disease might be related to specific interactions of CFH SCR7 with proteins expressed in the aging human RPE/choroid that could contribute to protein deposition in drusen. Yeast 2-hybrid (Y2H screens of a retinal pigment epithelium/choroid library derived from aged donors using CFH SCR7 baits detected an interaction with EFEMP1/Fibulin 3 (Fib3, which is the locus for an inherited macular degeneration and also accumulates basal to macular RPE in AMD. The CFH/Fib3 interaction was validated by co-immunoprecipitation of native proteins. Quantitative Y2H and ELISA assays with different recombinant protein constructs both demonstrated higher affinity for Fib3 for the disease-related CFH 402H variant. Immuno-labeling revealed colocalization of CFH and Fib3 in globular deposits within cholesterol-rich domains in soft drusen in two AMD donors homozygous for CFH 402H (H/H. This pattern of labeling was quite distinct from those seen in examples of eyes with Y/Y and H/Y genotypes. The CFH 402H/Fib3 interaction could contribute to the development of pathological aggregates in soft drusen in some patients and as such might provide a target for therapeutic intervention in some forms of AMD.

  4. Removal of phosphorus from wastewater using ferroxysorb sorption media produced from amd sludge

    Science.gov (United States)

    Sibrell, P.L.; Tucker, T.W.; Kehler, T.; Fletcher, J.W.

    2008-01-01

    Treatment of acid mine drainage (AMD), whether with lime, limestone, caustic or simple aeration, nearly always results in generation of a metal hydroxide sludge. Disposal of the sludge often constitutes a significant fraction of the operating cost for the AMD treatment plant. Research at the USGS - Leetown Science Center has shown that AMD sludge, with its high content of aluminum and iron oxides, has a high affinity of phosphorus (P). Anthropogenic sources of P are associated with eutrophication and degradation of aquatic environments, resulting in anoxic dead zones in certain sensitive waterways. In this paper, we describe a method of converting the AMD sludge from a liability into an asset - Ferroxysorb P removal media - which can be used to remove excess P from wastewater. Three different Ferroxysorb media samples were produced from differing AMD sources and tested for P removal. Adsorption isotherms confirmed that the media had a high sorption capacity for P, as high as 19,000 mg/kg. The technology was demonstrated at an active fish hatchery, where the media remained in service for over three months without stripping or regeneration. Over that period of time, the calculated P removal was 50%, even at a very low influent P concentration of 60 parts per billion. In summary, use of the AMD-derived Ferroxysorb sorption media will reduce AMD treatment costs while at the same time helping to resolve the pressing environmental issue of eutrophication and degradation of sensitive waterways.

  5. Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography.

    Science.gov (United States)

    Baumann, Bernhard; Gotzinger, Erich; Pircher, Michael; Sattmann, Harald; Schuutze, Christopher; Schlanitz, Ferdinand; Ahlers, Christian; Schmidt-Erfurth, Ursula; Hitzenberger, Christoph K

    2010-01-01

    We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures' tissue-inherent polarization properties.

  6. Long-term longitudinal study of patients treated with ranibizumab for neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit

    2014-01-01

    poorly to the treatment, and 20% obtain a condition with inactivity and good results. The majority of patients will need continuous active treatment. Long-term decline of visual acuity reflects the natural progression of the disease, however, insufficient treatment cannot be excluded leaving a potential...... of patients with nv-AMD can preserve visual acuity and expect long-term treatment beyond 2 years. Ocular complications and systemic adverse events remain few.......PURPOSE OF REVIEW: To review the current literature regarding long-term treatment beyond 2 years with anti-vascular endothelial growth factor (VEGF) inhibition for neovascular age-related macular degeneration (nv-AMD). RECENT FINDINGS: Only few studies of anti-VEGF treatment for nv-AMD exist beyond...

  7. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  8. Degenerate Gauss hypergeometric functions

    OpenAIRE

    Vidunas, Raimundas

    2004-01-01

    This is a study of terminating and ill-defined Gauss hypergeometric functions. Corresponding hypergeometric equations have a degenerate set of of 24 Kummer's solutions. We describe those solutions and relations between them.

  9. Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration.

    Science.gov (United States)

    Ozawa, Yoko; Shigeno, Yuta; Nagai, Norihiro; Suzuki, Misa; Kurihara, Toshihide; Minami, Sakiko; Hirano, Eri; Shinoda, Hajime; Kobayashi, Saori; Tsubota, Kazuo

    2017-08-29

    Lutein and zeaxanthin are suggested micronutrient supplements to prevent the progression of age-related macular degeneration (AMD), a leading cause of blindness worldwide. To monitor the levels of lutein/zeaxanthin in the macula, macular pigment optical density (MPOD) is measured. A commercially available device (MPSII®, Elektron Technology, Switzerland), using technology based on heterochromatic flicker photometry, can measure both absolute and estimated values of MPOD. However, whether the estimated value is applicable to Asian individuals and/or AMD patients remains to be determined. The absolute and estimated values of MPOD were measured using the MPSII® device in 77 participants with a best-corrected visual acuity (BCVA) > 0.099 (logMAR score). The studied eyes included 17 young (20-29 years) healthy, 26 aged (>50 years) healthy, 18 aged and AMD-fellow, and 16 aged AMD eyes. The mean BCVA among the groups were not significantly different. Both absolute and estimated values were measurable in all eyes of young healthy group. However, absolute values were measurable in only 57.7%, 66.7%, and 43.8%, of the aged healthy, AMD-fellow, and AMD groups, respectively, and 56.7% of the eyes included in the 3 aged groups. In contrast, the estimated value was measurable in 84.6%, 88.9% and 93.8% of the groups, respectively, and 88.3% of eyes in the pooled aged group. The estimated value was correlated with absolute value in individuals from all groups by Spearman's correlation coefficient analyses (young healthy: R 2  = 0.885, P = 0.0001; aged healthy: R 2  = 0.765, P = 0.001; AMD-fellow: R 2  = 0.851, P = 0.0001; and AMD: R 2  = 0.860, P = 0.013). Using the estimated value, significantly lower MPOD values were found in aged AMD-related eyes, which included both AMD-fellow and AMD eyes, compared with aged healthy eyes by Student's t-test (P = 0.02). Absolute, in contrast to estimated, value was measurable in a limited number of aged participants

  10. Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.

    Science.gov (United States)

    Owsley, Cynthia; Huisingh, Carrie; Clark, Mark E; Jackson, Gregory R; McGwin, Gerald

    2016-01-01

    To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. Eyes from adults ≥60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity and rod-mediated dark adaptation. A total of 1260 eyes were tested from 640 participants; 1007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as steps 2, 3 or 4). Adjusting for age and gender, early AMD eyes had two times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity and macular light sensitivity did not differ between normal eyes and early AMD eyes. Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity and spatial contrast sensitivity.

  11. Recent developments in the management of dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Buschini E

    2015-04-01

    Full Text Available Elisa Buschini, Antonio M Fea, Carlo A Lavia, Marco Nassisi, Giulia Pignata, Marta Zola, Federico M Grignolo Ospedale Oftalmico, Ophthalmic Section, Department of Clinical Pathophysiology, University of Turin, Turin, Italy Abstract: Dry age-related macular degeneration (AMD, also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%, dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6 are under evaluation, but the results are still uncertain. New strategies aim to 1 reduce or block drusen formation, 2 reduce or eliminate inflammation, 3 lower the accumulation of toxic by-products from the visual cycle, 4 reduce or eliminate retinal oxidative stress, 5 improve choroidal perfusion, 6 replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7 develop a target gene therapy. Keywords: dry AMD, geographic atrophy, new AMD therapy

  12. Categorization Task over a Touch Screen in Age-Related Macular Degeneration.

    Science.gov (United States)

    Lenoble, Quentin; Tran, Thi Ha Chau; Szaffarczyk, Sébastien; Boucart, Muriel

    2015-10-01

    In our modern society, many touch screen applications require hand-eye coordination to associate an icon with its specific contextual unit on phones, on computers, or in public transport. We assessed the ability of patients with age-related macular degeneration (AMD) to explore scenes and to associate a target (animal or object) with a unique congruent scene (e.g., to match a fish with the sea) presented between three other distractors on a touch screen computer. Twenty-four patients with AMD (64 to 90 years) with best-corrected visual acuity between 20/40 and 20/400 as well as 17 age-matched (60 to 94 years) and 15 young (22 to 34 years) participants with normal visual acuity had to match a target with a congruent scene by moving their index finger on a 22-in touch screen. Patients were as accurate (98.7% correct responses) as the age-matched control (98.9% correct responses) and young participants (99.3% correct responses) at performing the task. The duration of exploration was significantly longer for the AMD patients (mean, 4.13 seconds) compared with the age-matched group (mean, 2.96 seconds). The young participants were also significantly faster than the old group (mean, 0.93 seconds). The movement parameters of the older participants (patients and old control subjects) were affected compared with the young; the peak speed decreased (-8 cm/s) and the movement duration increased (+0.9 seconds) with age compared with the young group. People with AMD are able to perform a contextual association task on a touch screen with high accuracy. The AMD patients were specifically affected in the "exploration" phase; their accuracy and movement parameters did not differ from the old control group. Our study suggests that the decline associated with AMD is more focused on the duration of exploration than on movement parameters in touch screen use.

  13. Retinal vascular caliber and age-related macular degeneration in an Indian population from Singapore.

    Science.gov (United States)

    Chin, You Chuen; Wong, Tien Yin; Cheung, Chui Ming Gemmy; Cheung, Carol Yim-Lui; Zheng, Yingfeng; Mitchell, Paul; Huang, HuiQi; Wang, Jie Jin; Ikram, Mohammad Kamran

    2014-08-01

    To examine the association between retinal vascular caliber and early age-related macular degeneration (AMD) in an Indian population. A total of 3112 Indian participants aged ≥40 years from the population-based Singapore Indian Eye Study who had data available on retinal vascular caliber measurements and AMD status were included. Retinal arteriolar and venular calibers were measured from digital photographs using computer-assisted software according to a standardized protocol. Images of the macular region were graded according to the modified Wisconsin age-related maculopathy grading system. Right eyes were selected for analyses. Binary logistic regression models were used to assess the association, adjusting for age, sex, systolic blood pressure, total cholesterol, random blood glucose, body mass index, and the companion retinal vascular caliber. A total of 107 participants (3.4%) were diagnosed with early AMD. Neither arteriolar nor venular caliber was related to AMD. For early AMD, the age-, sex-, and companion retinal vascular caliber-adjusted odds ratio (OR) per standard deviation (SD) decrease in arteriolar caliber was 0.95 (95% CI 0.84-1.31; p = 0.671), and per SD increase in venular caliber was OR: 0.96 (95% CI: 0.77-1.20); p = 0.714. No trend was found after categorizing retinal vascular calibers into quartiles. Multivariate adjustment and stratified analyses did not alter these results. Retinal vascular calibers were not related to early AMD among Indian participants. These findings differ from those of several previous studies performed in Caucasian and Asian populations.

  14. OPTIMAL MANAGEMENT OF PIGMENT EPITHELIAL DETACHMENTS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Khanani, Arshad M; Eichenbaum, David; Schlottmann, Patricio G; Tuomi, Lisa; Sarraf, David

    2018-04-24

    This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature. A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD. Studies illustrated that anti-vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution. Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  15. Rapid glutamate receptor 2 trafficking during retinal degeneration

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    Lin Yanhua

    2012-02-01

    Full Text Available Abstract Background Retinal degenerations, such as age-related macular degeneration (AMD and retinitis pigmentosa (RP, are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2 subunit and its trafficking may be modulated in retinal degenerations. Results Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD. We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1 and postsynaptic density protein 95 (PSD-95, were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites. Conclusions All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

  16. CREB1/ATF1 activation in photoreceptor degeneration and protection.

    Science.gov (United States)

    Beltran, William A; Allore, Heather G; Johnson, Elizabeth; Towle, Virginia; Tao, Weng; Acland, Gregory M; Aguirre, Gustavo D; Zeiss, Caroline J

    2009-11-01

    The cAMP response element binding protein 1 (CREB1) and activating transcription factor 1 (ATF1) are closely related members of the bZIP superfamily of transcription factors. Both are activated in response to a wide array of stimuli, including cellular stress. This study was conducted to assess the CREB1/ATF1 pathway in photoreceptor disease and protection. The expression levels of p-CREB1, CREB1, and ATF1 were examined by immunoblot and immunohistochemistry in normal canine retina and retinas of several canine models of retinal degeneration (rcd1, rcd2, erd, prcd, XLPRA1, XLPRA2, T4R RHO). Humans retinas affected with age-related macular degeneration (AMD) were also examined. p-CREB1/ATF1 immunolabeling was assessed in normal and rcd1 dogs treated with ciliary neurotrophic factor (CNTF), to examine the effect of a neuroprotective stimulus on activation of CREB1/ATF1. Native CREB1 and ATF1 as well as phosphorylated CREB1/ATF1 was examined in normal canine retina by immunoblot. The p-CREB1 antibody identified phosphorylated CREB1 and ATF1 and labeled the inner retina only in normal dogs. In degenerate canine and human retinas, strong immunolabeling appeared in rod and cone photoreceptors, indicating increased expression of native CREB1 and ATF1, as well as increased phosphorylation of these proteins. Retinal protection by CNTF in rcd1 dogs was accompanied by a significant increase in the number of p-CREB1/ATF1-labeled photoreceptor nuclei. Positive association of CREB1/ATF1 phosphorylation with photoreceptor protection suggests that it may contribute to an innate protective response. These data identify a signaling mechanism in rods and cones of potential importance for therapies of RP and AMD.

  17. Effect of substance P on recovery from laser-induced retinal degeneration.

    Science.gov (United States)

    Hong, Hyun Sook; Kim, Suna; Nam, Seungwoo; Um, Jihyun; Kim, Yeong Hoon; Son, Youngsook

    2015-01-01

    Retinal degeneration is caused by neovascularization and persistent inflammation in the retinal pigment epithelium (RPE) and choroid, and causes serious eye disease including age-related macular degeneration (AMD). Thus, inhibiting inflammation and neovascularization may be a primary approach to protect the retina from degeneration. The purpose of this study was to determine whether substance P (SP), which can suppress inflammation and mobilize stem cells, can protect the RPE from degeneration. The effect of SP was evaluated by analyzing systemic inflammation, cell survival, and neovascularization within the argon laser-injured retina of mice. At 1 week postinjury, the SP-treated group had lower tumor necrosis factor-alpha and higher interleukin-10 serum concentrations, and a more intact retinal structure compared to the vehicle-treated group. In mice administered SP repeatedly for 4 weeks, the retinal structure appeared normal and showed sparse neovascularization, whereas the vehicle-treated group showed severe retinal destruction and dense neovascularization. Moreover, the efficacy of SP was identical to that of mesenchymal stem cells that were transplanted into the vitreous after retinal injury. This study highlights the potential for the endogenous neuropeptide SP as a treatment for retinal damage to prevent conditions such as AMD. © 2015 by the Wound Healing Society.

  18. Kiibitootja AMD on võitmas turuosa suure rivaali Inteli käest / Lauri Matsulevitsh

    Index Scriptorium Estoniae

    Matsulevitsh, Lauri

    2006-01-01

    Arvutiprotsessorite tootja Advanced Micro Devices (AMD) näitas oma lõppenud kvartalis teenitud kasumiga, et hakkab konkurent Intelile järgi jõudma. Diagramm: Aktsia hind. Kommenteerib Peeter Teder

  19. Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina

    Directory of Open Access Journals (Sweden)

    Singh Brij B

    2011-08-01

    Full Text Available Abstract Background Alzheimer's disease (AD and age-related macular degeneration (AMD share several pathological hallmarks including β-amyloid (Aβ accumulation, oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely multi-factorial with several factors such as diet, environment, and genetic susceptibility participating in the pathogenesis of these diseases. Epidemiological studies correlated high plasma cholesterol levels with high incidence of AD, and feeding rabbits with a diet rich in cholesterol has been shown to induce AD-like pathology in rabbit brain. High intake of cholesterol and saturated fat were also long been suspected to increase the risk for AMD. However, the extent to which cholesterol-enriched diet may also cause AMD-like features in rabbit retinas is not well known. Methods Male New Zealand white rabbits were fed normal chow or a 2% cholesterol-enriched diet for 12 weeks. At necropsy, animals were perfused with Dulbecco's phosphate-buffered saline and the eyes were promptly removed. One eye of each animal was used for immunohistochemistry and retina dissected from the other eye was used for Western blot, ELISA assays, spectrophotometry and mass spectrometry analyses. Results Increased levels of Aβ, decreased levels of the anti-apoptotic protein Bcl-2, increased levels of the pro-apoptotic Bax and gadd153 proteins, emergence of TUNEL-positive cells, and increased generation of reactive oxygen species were found in retinas from cholesterol-fed compared to normal chow-fed rabbits. Additionally, astrogliosis, drusen-like debris and cholesterol accumulations in retinas from cholesterol-fed rabbits were observed. As several lines of evidence suggest that oxidized cholesterol metabolites (oxysterols may be the link by which cholesterol contributes to the pathogenesis of AMD, we determined levels of oxysterols and found a dramatic increase in levels of oxysterols in retinas from cholesterol-fed rabbits

  20. Chemical alterations in three clayey soils from percolation and interaction with acid mine drainage (AMD

    Directory of Open Access Journals (Sweden)

    Emem-Obong Emmanuel Agbenyeku

    2016-07-01

    Full Text Available The issues of acid mine drainage (AMD from mining activities is not a new phenomenon to the present day developing South Africa as well as in most developed countries around the globe. However, the persistent rise in environmental contamination in South Africa is drastically attracting massive concerns. Vital concerns of AMD in South Africa still remain the threat to soil, surface, subsurface and ground water reserves among others, which consequentially impact human and environmental health. This insistent challenge has given rise to the need for investigating the buffering efficacy of clayey mineral soils for use as natural contaminant barriers to contaminant species from AMD. Therefore, the study presented herein, was channelled towards assessing the chemical alterations in three clayey soils from permeation and interaction with AMD via successive protracted percolation up to 18–25 pore volume passage of AMD through the respective soil medium. The final hydraulic conductivity measured, ranged between 1.3 × 10−11 m/s and 1.5 × 10−11 m/s. The obtained pH, electrical conductivity and solute breakthrough curves indicated the soils had low acid-buffering efficacies. Chemical species such as Na, Co and SO42− were highly dissolved due to attack on the soil grains by AMD. Chemical species were also released from the soils including the dissolution of metals and desorption of chemical species from AMD attack. As such, the study revealed that the buffering efficacies of the respective tested clayey soils to AMD chemical contaminants were generally ineffective.

  1. Disc degeneration: current surgical options

    Directory of Open Access Journals (Sweden)

    C Schizas

    2010-10-01

    Full Text Available Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

  2. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  3. Gene Ontology and KEGG Enrichment Analyses of Genes Related to Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    2014-01-01

    Full Text Available Identifying disease genes is one of the most important topics in biomedicine and may facilitate studies on the mechanisms underlying disease. Age-related macular degeneration (AMD is a serious eye disease; it typically affects older adults and results in a loss of vision due to retina damage. In this study, we attempt to develop an effective method for distinguishing AMD-related genes. Gene ontology and KEGG enrichment analyses of known AMD-related genes were performed, and a classification system was established. In detail, each gene was encoded into a vector by extracting enrichment scores of the gene set, including it and its direct neighbors in STRING, and gene ontology terms or KEGG pathways. Then certain feature-selection methods, including minimum redundancy maximum relevance and incremental feature selection, were adopted to extract key features for the classification system. As a result, 720 GO terms and 11 KEGG pathways were deemed the most important factors for predicting AMD-related genes.

  4. Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

    Science.gov (United States)

    Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

  5. Multimodal scanning laser ophthalmoscopy for image guided treatment of age-related macular degeneration

    Science.gov (United States)

    Hammer, Daniel X.; Ferguson, R. D.; Patel, Ankit H.; Iftimia, Nicusor V.; Mujat, Mircea; Husain, Deeba

    2009-02-01

    Subretinal neovascular membranes (SRNM) are a deleterious complication of laser eye injury and retinal diseases such as age-related macular degeneration (AMD), choroiditis, and myopic retinopathy. Photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) drugs are approved treatment methods. PDT acts by selective dye accumulation, activation by laser light, and disruption and clotting of the new leaky vessels. However, PDT surgery is currently not image-guided, nor does it proceed in an efficient or automated manner. This may contribute to the high rate of re-treatment. We have developed a multimodal scanning laser ophthalmoscope (SLO) for automated diagnosis and image-guided treatment of SRNMs associated with AMD. The system combines line scanning laser ophthalmoscopy (LSLO), fluorescein angiography (FA), indocyanine green angiography (ICGA), PDT laser delivery, and retinal tracking in a compact, efficient platform. This paper describes the system hardware and software design, performance characterization, and automated patient imaging and treatment session procedures and algorithms. Also, we present initial imaging and tracking measurements on normal subjects and automated lesion demarcation and sizing analysis of previously acquired angiograms. Future pre-clinical testing includes line scanning angiography and PDT treatment of AMD subjects. The automated acquisition procedure, enhanced and expedited data post-processing, and innovative image visualization and interpretation tools provided by the multimodal retinal imager may eventually aid in the diagnosis, treatment, and prognosis of AMD and other retinal diseases.

  6. Influence of new societal factors on neovascular age-related macular degeneration outcomes.

    Science.gov (United States)

    Giocanti-Aurégan, Audrey; Chbat, Elige; Darugar, Adil; Morel, Christophe; Morin, Bruno; Conrath, John; Devin, François

    2018-02-01

    To assess the impact of unstudied societal factors for neovascular age-related macular degeneration (nAMD) on functional outcomes after anti-VEGFs. Charts of 94 nAMD patients treated in the Monticelli-Paradis Centre, Marseille, France, were reviewed. Phone interviews were conducted to assess societal factors, including transportation, living status, daily reading and social security scheme (SSS). Primary outcome was the impact of family support and disease burden on functional improvement in nAMD. Between baseline and month 24 (M24), 42.4% of the variability in best-corrected visual acuity (BCVA) was explained by the cumulative effect of the following societal factors: intermittent out-patient follow-up, marital status, daily reading, transportation type, commuting time. No isolated societal factor significantly correlated with ETDRS BCVA severity at M24. A trend to correlation was observed between the EDTRS score at M24 and the SSS (P = 0.076), economic burden (P = 0.075), time between diagnosis and treatment initiation (P = 0.070). A significant correlation was found for the disease burdensome on the patient (P = 0.034) and low vision rehabilitation (P = 0.014). Societal factors could influence functional outcomes in nAMD patients treated with anti-VEGFs. They could contribute to the healing process or sustain disease progression.

  7. Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration

    Science.gov (United States)

    Klein, Michael L.; Ferris, Frederick L.; Francis, Peter J.; Lindblad, Anne S.; Chew, Emily Y.; Hamon, Sara C.; Ott, Jurg

    2009-01-01

    Purpose To determine if genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Design Prospective analysis of participants in a randomized controlled clinical trial. Participants 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS). Methods Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed. Main Outcome Measures Genotype frequencies and change in cumulative area of GA. Results The mean growth rate of geographic atrophy for the 114 eyes was 1.79 mm2/year (range= 0.17–4.76 mm2/year). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3genes. For the single nucleotide polymorphism (SNP) rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared to the homozygous non-risk genotype (unadjusted p-value = 0.002; Bonferroni corrected p-value = 0.014) and for allelic association(Bonferroni corrected p-value = 0.011). Analyses of other measures of geographic atrophy progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype. Conclusion GA growth rates calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, and TLR3 genes. There was a nominally statistically significant association

  8. Prevalence of depression, anxiety, adjustment disorders, and somatoform disorders in patients with age-related macular degeneration in Germany

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    Jacob, Louis

    2017-02-01

    Full Text Available Aims: The purpose of this study was to analyze the prevalence of depression, anxiety, adjustment disorders, and somatoform disorders in patients diagnosed with age-related macular degeneration (AMD in Germany.Methods: This study included 7,580 patients between the ages of 40 and 90 diagnosed with AMD between January 2011 and December 2014 in 1,072 primary care practices (index date. The last follow-up was in July 2016. We also included 7,580 controls without AMD, which were matched (1:1 to the AMD cases by age, sex, type of health insurance (private or statutory, physician, and Charlson comorbidity score as a generic marker of comorbidity. The outcome of the study was the prevalence of depression, anxiety, adjustment disorders, and somatoform disorders recorded in the database between the index date and the end of follow-up. Results: The mean age among subjects was 75.7 years (SD=10.1 years, 34.0% were men, and 7.8% had private health insurance coverage. The Charlson comorbidity index was 2.0 (SD=1.8. Depression was the most frequent disease (33.7% in AMD patients versus 27.3% in controls, followed by somatoform disorders (19.6% and 16.7%, adjustment disorders (14.8% and 10.5%, and anxiety disorders (11.7% and 8.2%. Depression (OR=1.37, 95% CI: 1.27–1.47, anxiety (OR=1.50, 95% CI: 1.35–1.67, adjustment disorders (OR=1.50, 95% CI: 1.36–1.65, and somatoform disorders (OR=1.22, 95% CI: 1.12–1.32 were all positively associated with AMD. Conclusion: Overall, a significant association was found between AMD and depression, anxiety, adjustment disorders, and somatoform disorders.

  9. Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

    Science.gov (United States)

    McKay, Gareth J.; Patterson, Chris C.; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R.; Ho, Lintje; de Jong, Paulus T.V.M.; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D.; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M.; Peter, Inga; Webster, Andrew R.; Moore, Anthony T.; Yates, John R.W.; Cipriani, Valentina; Fritsche, Lars G.; Weber, Bernhard H.F.; Keilhauer, Claudia N.; Lotery, Andrew J.; Ennis, Sarah; Klein, Michael L.; Francis, Peter J.; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B.; Weeks, Daniel E.; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R.; Wright, Alan F.; Hayward, Caroline; Baird, Paul N.; Guymer, Robyn H.; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

    2011-01-01

    Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. PMID:21882290

  10. Clinical course over two to six years of age-related macular degeneration with or without radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kameda, Takanori; Noami, Sachiyo; Akita, Joe [Kyoto Univ. (Japan). Graduate School of Medicine] (and others)

    2002-10-01

    We previously reported about the long-term outcome as long as three years after radiation therapy for choroidal neovascularization secondary to age-related macular degeneration (AMD). Though MPS (Macular Photocoagulation Study) Group reported the long-term natural course of AMD, such reports have not been provided concerned about Japanese AMD patients. Furthermore, there is not report that revealed the course of AMD with radiation therapy more than three years. We evaluated the long-term natural course and long-term effect of low-dose radiation on AMD. The fundus ophthalmoscopic evaluation and visual outcome were compared retrospectively among control group and two treated groups; seven eyes received 10 Gy, and eight eyes 20 Gy. The control group consisted of 10 eyes without treatment. All patients were followed at least four years, and the average follow-up duration was 6.56 years. The course of median visual acuity without treatment showed the similar result to that of MPS Group's report. In control group, visual acuity (VA) after four years was better in no eyes, unchanged in two eyes, and worse in eight eyes; in treated group, better in four eyes, unchanged in one eye, and worse in ten eyes. After four years VA was kept 20/200 or higher in 2 eyes without treatment, 4 eyes with 10 Gy, and 4 eyes with 20 Gy of radiation. Then maximum VA was 20/125 with no treatment, and 20/50 with radiation therapy. The natural course of the AMD of Japanese patients showed similar results to US patients. All eyes of AMD withort treatment got worse in VA, and some showed better outcome with radiation therapy; but it was not statistically significant. (author)

  11. Central retinal function as measured by the multifocal electroretinogram and flicker perimetry in early age-related macular degeneration.

    Science.gov (United States)

    Gin, Thomas J; Luu, Chi D; Guymer, Robyn H

    2011-11-29

    To determine the retinal function in early age-related macular degeneration (AMD) assessed by the multifocal electroretinogram (mfERG) and flicker perimetry and to seek a relationship between local objective mfERG parameters and subjective flicker perimetry thresholds. mfERG and flicker perimetry were performed in 15 patients (15 eyes) with early AMD and 14 controls (14 eyes) of similar age. The mfERG P1 response amplitude density (nV/deg²) and P1 implicit time of the first-order kernel and the flicker thresholds of each concentric ring were analyzed. The relationship between individual mfERG responses and the corresponding individual flicker sensitivity outcomes was determined. The mfERG response amplitude of the central ring (ring 1) was significantly reduced in early AMD eyes compared with the controls (P = 0.009). No significant difference in mfERG amplitude between early AMD and control eyes was detected in the other rings. The mfERG implicit time was significantly increased in the early AMD eyes but only within the central four rings of 12°. A significant reduction in flicker sensitivity was also detected in early AMD eyes but only within the central 6°. There was a significant, moderate correlation (r = -0.477; P flicker sensitivity from the same tested locations within the central 6°. There was a weak correlation (r = 0.200; P = 0.014) between mfERG amplitude and flicker sensitivity. Both mfERG and flicker perimetry show abnormal retinal function, but only in the very central macula, in early AMD. A novel relationship between mfERG and flicker sensitivity should enhance the clinical monitoring of disease progression.

  12. Hyperopic refractive error and shorter axial length are associated with age-related macular degeneration: the Singapore Malay Eye Study.

    Science.gov (United States)

    Lavanya, Raghavan; Kawasaki, Ryo; Tay, Wan Ting; Cheung, Gemmy C M; Mitchell, Paul; Saw, Seang-Mei; Aung, Tin; Wong, Tien Y

    2010-12-01

    To describe the association between refractive errors, ocular biometry, and age-related macular degeneration (AMD) in an Asian Malay population in Singapore. A population-based study of 3280 Malay individuals aged 40 to 80 years was conducted in Singapore. Early- and late-AMD signs were graded from retinal photographs according to the Wisconsin grading system. Autorefraction, followed by subjective refraction, was performed to obtain spherical equivalent refraction (SER) in diopters, with emmetropia defined as SER -0.5 to +0.5 D, hyperopia as > +0.5 D, and myopia as education, height, and systolic blood pressure. Each diopter increase in hyperopic refraction and each millimeter decrease in axial length was associated with an 8% (OR, 1.08; CI, 1.01-1.16; P = 0.03) and 29% (OR, 1.29; CI, 1.06-1.57; P = 0.01) increased risk of early AMD, respectively. No significant association was noted of refractive error and ocular biometry with late AMD. Hyperopic refractive error and shorter axial length are associated with early AMD in Asian eyes.

  13. A Delphi Study to Detect Deficiencies and Propose Actions in Real Life Treatment of Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Alfredo García-Layana

    2014-01-01

    Full Text Available Purpose. Spanish retina specialists were surveyed in order to propose actions to decrease deficiencies in real-life neovascular age macular degeneration treatment (nv-AMD. Methods. One hundred experts, members of the Spanish Vitreoretinal Society (SERV, were invited to complete an online survey of 52 statements about nv-AMD management with a modified Delphi methodology. Four rounds were performed using a 5-point Linkert scale. Recommendations were developed after analyzing the differences between the results and the SERV guidelines recommendations. Results. Eighty-seven specialists completed all the Delphi rounds. Once major potential deficiencies in real-life nv-AMD treatment were identified, 15 recommendations were developed with a high level of agreement. Consensus statements to reduce the burden of the disease included the use of treat and extend regimen and to reduce the amount of diagnostic tests during the loading phase and training technical staff to perform these tests and reduce the time between relapse detection and reinjection, as well as establishing patient referral protocols to outside general ophthalmology clinics. Conclusion. The level of agreement with the final recommendations for nv-AMD treatment among Spanish retinal specialist was high indicating that some actions could be applied in order to reduce the deficiencies in real-life nv-AMD treatment.

  14. Dissecting microRNA dysregulation in age-related macular degeneration: new targets for eye gene therapy.

    Science.gov (United States)

    Askou, Anne Louise; Alsing, Sidsel; Holmgaard, Andreas; Bek, Toke; Corydon, Thomas J

    2018-02-01

    MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age-related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype-specific miRNA profiles for late-stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. [OCT Angiography of RPE Tears in Exudative AMD: Morpohological Analysis of the Choriocapillaris and the RPE].

    Science.gov (United States)

    Gutfleisch, Matthias; Rothaus, Kai; Farecki, Marie-Louise; Faatz, Henrik; Heimes-Bussmann, Britta; Gunnemann, Frederic; Ziegler, Martin; Papapostolou, Ioannis; Lommatzsch, Albrecht; Pauleikoff, Daniel

    2017-09-01

    Background Retinal pigment epithelium (RPE) tears are a typical complication of vascular pigment epithelium detachment in age-related macular degeneration (AMD). During proactive intense anti-VEGF therapy, stabilisation or improvement of function may occur. With the new method of OCT angiography (OCT-A), retinal vessels and flow density can be quantified. This pilot study investigates changes in the choriocapillars (CC) in areas with increasing FAF in OCT following an RPE-tear. Methods In six eyes with an RPE-tear, prospectively initially and every three months thereafter, multimodal imaging was performed, including fundus autofluorescence (FAF) (HRA2, Heidelberg Engineering, Heidelberg, Deutschland) and OCT-A (RTVue XR Avanti, SSDA-Modus, Angiovue, Optovue, Freemont, CA, USA). With interactive MATLAB-software (MATLAB, MathWorks, Natick, MA, USA), FAF and OCT were geometrically superimposed. With the help of the Fiji software (National Institutes of Health, Bethesda, MD, USA), areas with increasing FAF flow intensity in OCT-A with CC-segmentation were measured during an average follow-up period of 12 months. Results We measured a reduction in the RPE-free area - due to an increase in autofluorescence tissue - of an average of 2.94 mm 2 (SD 2.1 mm 2 ; 42.1% of initial RPE-free area) in the boundary area of RPE-tears. At the end of the different follow-ups, some patients exhibited lower flow density in areas of regenerated autofluorescence than the initial findings. On the other hand, in some follow-ups, the same or increased flow density was seen. Conclusion In this pilot study, OCT-A was tested to analyse the structure of CC in areas of regenerated FAF after RPE-tears. Using external image editing software, FAF and OCT-A were compared during the follow-up. Thus apparent initial regression of the CC in the area mentioned above could be observed. During the follow-up and development of autofluorescent SHT, CC also regenerates up to the level of the initial

  16. Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

    Directory of Open Access Journals (Sweden)

    Dimitrios Brouzas

    2009-08-01

    Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

  17. Automated detection of exudative age-related macular degeneration in spectral domain optical coherence tomography using deep learning.

    Science.gov (United States)

    Treder, Maximilian; Lauermann, Jost Lennart; Eter, Nicole

    2018-02-01

    Our purpose was to use deep learning for the automated detection of age-related macular degeneration (AMD) in spectral domain optical coherence tomography (SD-OCT). A total of 1112 cross-section SD-OCT images of patients with exudative AMD and a healthy control group were used for this study. In the first step, an open-source multi-layer deep convolutional neural network (DCNN), which was pretrained with 1.2 million images from ImageNet, was trained and validated with 1012 cross-section SD-OCT scans (AMD: 701; healthy: 311). During this procedure training accuracy, validation accuracy and cross-entropy were computed. The open-source deep learning framework TensorFlow™ (Google Inc., Mountain View, CA, USA) was used to accelerate the deep learning process. In the last step, a created DCNN classifier, using the information of the above mentioned deep learning process, was tested in detecting 100 untrained cross-section SD-OCT images (AMD: 50; healthy: 50). Therefore, an AMD testing score was computed: 0.98 or higher was presumed for AMD. After an iteration of 500 training steps, the training accuracy and validation accuracies were 100%, and the cross-entropy was 0.005. The average AMD scores were 0.997 ± 0.003 in the AMD testing group and 0.9203 ± 0.085 in the healthy comparison group. The difference between the two groups was highly significant (p < 0.001). With a deep learning-based approach using TensorFlow™, it is possible to detect AMD in SD-OCT with high sensitivity and specificity. With more image data, an expansion of this classifier for other macular diseases or further details in AMD is possible, suggesting an application for this model as a support in clinical decisions. Another possible future application would involve the individual prediction of the progress and success of therapy for different diseases by automatically detecting hidden image information.

  18. Automatic segmentation of nine retinal layer boundaries in OCT images of non-exudative AMD patients using deep learning and graph search.

    Science.gov (United States)

    Fang, Leyuan; Cunefare, David; Wang, Chong; Guymer, Robyn H; Li, Shutao; Farsiu, Sina

    2017-05-01

    We present a novel framework combining convolutional neural networks (CNN) and graph search methods (termed as CNN-GS) for the automatic segmentation of nine layer boundaries on retinal optical coherence tomography (OCT) images. CNN-GS first utilizes a CNN to extract features of specific retinal layer boundaries and train a corresponding classifier to delineate a pilot estimate of the eight layers. Next, a graph search method uses the probability maps created from the CNN to find the final boundaries. We validated our proposed method on 60 volumes (2915 B-scans) from 20 human eyes with non-exudative age-related macular degeneration (AMD), which attested to effectiveness of our proposed technique.

  19. A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration.

    Science.gov (United States)

    Schmidt-Erfurth, U; Klimscha, S; Waldstein, S M; Bogunović, H

    2017-01-01

    Optical coherence tomography (OCT) has become an established diagnostic technology in the clinical management of age-related macular degeneration (AMD). OCT is being used for primary diagnosis, evaluation of therapeutic efficacy, and long-term monitoring. Computer-based advances in image analysis provide complementary imaging tools such as OCT angiography, further novel automated analysis methods as well as feature detection and prediction of prognosis in disease and therapy by machine learning. In early AMD, pathognomonic features such as drusen, pseudodrusen, and abnormalities of the retinal pigment epithelium (RPE) can be imaged in a qualitative and quantitative way to identify early signs of disease activity and define the risk of progression. In advanced AMD, disease activity can be monitored clearly by qualitative and quantified analyses of fluid pooling, such as intraretinal cystoid fluid, subretinal fluid, and pigment epithelial detachment (PED). Moreover, machine learning methods detect a large spectrum of new biomarkers. Evaluation of treatment efficacy and definition of optimal therapeutic regimens are an important aim in managing neovascular AMD. In atrophic AMD hallmarked by geographic atrophy (GA), advanced spectral domain (SD)-OCT imaging largely replaces conventional fundus autofluorescence (FAF) as it adds insight into the condition of the neurosensory layers and associated alterations at the level of the RPE and choroid. Exploration of imaging features by computerized methods has just begun but has already opened relevant and reliable horizons for the optimal use of OCT imaging for individualized and population-based management of AMD-the leading retinal epidemic of modern times.

  20. NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components

    Science.gov (United States)

    Doyle, Sarah L; Campbell, Matthew; Ozaki, Ema; Salomon, Robert G; Mori, Andres; Kenna, Paul F; Farrar, Gwyneth Jane; Kiang, Anna-Sophia; Humphries, Marian M; Lavelle, Ed C; O’Neill, Luke A J; Hollyfield, Joe G; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Drusen accumulation is the major pathological hallmark common to both dry and wet AMD. Although activation of the immune system has been implicated in disease progression, the pathways involved are unclear. Here we show that drusen isolated from donor AMD eyes activates the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, causing secretion of interleukin-1β (IL-1β) and IL-18. Drusen component C1Q also activates the NLRP3 inflammasome. Moreover, the oxidative-stress–related protein-modification carboxyethylpyrrole (CEP), a biomarker of AMD, primes the inflammasome. We found cleaved caspase-1 and NLRP3 in activated macrophages in the retinas of mice immunized with CEP-adducted mouse serum albumin, modeling a dry-AMD–like pathology. We show that laser-induced choroidal neovascularization (CNV), a mouse model of wet AMD, is exacerbated in Nlrp3−/− but not Il1r1−/− mice, directly implicating IL-18 in the regulation of CNV development. These findings indicate a protective role for NLRP3 and IL-18 in the progression of AMD. PMID:22484808

  1. Excess lead in the neural retina in age-related macular degeneration.

    Science.gov (United States)

    Erie, Jay C; Good, Jonathan A; Butz, John A

    2009-12-01

    To measure lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration (AMD). Laboratory investigation. Lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium [RPE]-choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) were determined by using inductively coupled plasma-mass spectrometry. Severity of AMD was graded by using color fundus photographs and the Minnesota Grading System. Differences in metal concentrations were compared by using Wilcoxon rank-sum tests. The neural retinas of subjects with AMD had increased lead concentrations (median, 12.0 ng/g; 25% to 75% interquartile range, 8 to 18 ng/g; n = 25) compared with normal subjects (median, 8.0 ng/g; 25% to 75% interquartile range, 0 to 11 ng/g; P = .04; n = 36). There was no difference in lead concentration in the RPE-choroid complex between subjects with AMD (median, 198 ng/g; 25% to 75% interquartile range, 87 to 381 ng/g) and normal subjects (median, 172 ng/g; 25% to 75% interquartile range, 100 to 288 ng/g; P = .25). Cadmium concentration in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.8 microg/g) and RPE-choroid complex (median, 2.2 microg/g; 25% to 75% interquartile range, 1.8 to 3.7 microg/g) in subjects with AMD was not different from concentrations in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.4 microg/g; P = .32) and RPE-choroid complex (median, 1.5 microg/g; 25% to 75% interquartile range, 0.9 to 2.5 microg/g; P = .12) of normal subjects. AMD is associated with excess lead in the neural retina, and this relationship suggests that metal homeostasis in AMD eyes is different from normal.

  2. One-year outcome of ranibizumab for neovascular age-related macular degeneration: a thorough analysis in a real-world clinical setting.

    Science.gov (United States)

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2014-01-01

    To verify the safety and efficacy of ranibizumab in neovascular age-related macular degeneration (nAMD) and factors influencing the outcome in a real-world setting. Retrospective 12-month follow-up analysis of 100 naive nAMD eyes treated with as-needed ranibizumab. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), lesion, and leakage size were recorded. Type and characteristics of lesions and indicators of protocol adherence were analyzed. Mean BCVA at baseline was 61.6 ± 14.8 Early Treatment Diabetic Retinopathy Study letters and 59.6 ± 16 at 12 months. Sixty-three eyes maintained or improved BCVA; the number of injections and follow-up visits were 4.8 and 5.1, respectively. First injection and pro re nata retreatments were administered 22.7 and 20.5 days after prescription, respectively. Seventy-two eyes received 3 initial monthly injections. Patients were not reinjected despite BCVA loss >5 letters one or more times in 37% of cases. No adverse events were reported. The CRT diminished by 26 ± 101 μm; choroidal neovascularization size and leakage area increased by 0.53 ± 1.31 mm² and 0.34 ± 1.33 mm², respectively. The BCVA gain was correlated with CRT reduction (r = 0.24, p = 0.016), mean baseline BCVA (r = -0.25, p = 0.01), age (r = -0.25, p = 0.01), and decrease in CNV size and leakage area (r = 0.56 and r = 0.59, respectively, p<0.001). Our results compare unfavorably with those of controlled trials. Treatment and follow-up regimens in real-world settings seem to have a major role in determining outcome. Lower age and BCVA at baseline were associated with better response to treatment.

  3. One-year real-world outcomes in patients receiving fixed-dosing aflibercept for neovascular age-related macular degeneration.

    Science.gov (United States)

    Almuhtaseb, H; Kanavati, S; Rufai, S R; Lotery, A J

    2017-06-01

    PurposeTo investigate 1-year visual and anatomic outcomes of intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) given at a fixed 8-weekly interval.MethodsRetrospective, single-practice data analysis from an electronic medical record system of 255 eyes (223 patients) with treatment-naïve nAMD receiving 8-weekly aflibercept.ResultsMean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) improved from 0.66 at baseline to 0.50 at month 11 (P<0.0001). Mean central retinal thickness (CRT) decreased from 311 μm at baseline to 211 μm at month 11 (P<0.0001). Our mean VA gain of eight ETDRS letters was comparable to the VIEW 1 and VIEW 2 Trials' results at the end of year 1. After loading at month 5, mean BCVA was 0.48 (P<0.0001), and mean CRT was 235 μm. At month 5, 143 eyes (56%) were inactive defined by the absence of macular haemorrhage and intraretinal fluid (IRF) and subretinal fluid (SRF) on optical coherence tomography, and 112 eyes (44%) remained active. At month 11, 136 eyes (53%) were inactive, and 119 eyes (47%) remained active. At month 11, 77% of inactive eyes after loading remained inactive, and 77% of the active eyes after loading remained active. At month 11, mean BCVA of the inactive group was 0.51, and mean BCVA of the active group was 0.48 (P=0.54).ConclusionsAflibercept administered by fixed dosing over 1 year improved VA and macular morphology in treatment-naïve eyes. Active lesions at month 11 do not have worse VA outcomes compared with inactive lesions. The macular status after loading is a reliable indicator of disease activity at the end of year 1.

  4. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  5. Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial.

    Science.gov (United States)

    Korobelnik, Jean-François; Rougier, Marie-Bénédicte; Delyfer, Marie-Noëlle; Bron, Alain; Merle, Bénédicte M J; Savel, Hélène; Chêne, Geneviève; Delcourt, Cécile; Creuzot-Garcher, Catherine

    2017-11-01

    Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD). To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD. Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors. Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the

  6. Fate of Fe, As in Acid Mine Drainage (AMD) was created Disused Metal Mine

    Science.gov (United States)

    Yu, H.; Kang, D. H.; Kim, S. J.; So, Y.

    2015-12-01

    This study is a natural reduction of Fe and As in AMD. AMD is produced by oxidation of pyrite, the iron, the sulfate mineral dissolution action. It is generated by the sulfide minerals, water, oxygen, the reaction of microorganisms in the underground. AMD is low pH due to dissolved minerals in the mine are different kinds of heavy metals will leach. If the flow out of mines and react with dissolved oxygen (DO) is increased, due to oxidation and microbiological activity of the Fe it is precipitated biomat is produced. This study area is Ilgwng disused mines in the Republic of Korea Busan Gijanggun. March to September 2010 taken by the AMD and biomat analyze Fe and As. The main mineral is Chalcopyrite (Cu2Fe2S4), Arsenopyrite (FeAsS), Pyrite (FeS2), Pyrrhotite (Fe1-xS), Sphalerite (ZnS), Galena (PbS), Scheelite (CaWO4), Wolframite ((Fe, Mn)WO4) and the like. Analysis of the AMD of underground pH 2.4~2.8, DO 1.3~4.8mg/L, Fe 474.3~178.8mg/L, As 0~3.2mg/L. Analysis AMD of the flow out of mine pH 2.3~2.9, DO 6.7~9.5mg/L, Fe 81.9~438.7L, As 0~2.8mg/L. The content of Fe in the biomat is 244.242mg/kg, the content of As is 5647mg/kg in the adsorption reaction of the Fe. AMD of disused metal mine mineral leaching occur in a reducing environment, in an oxidizing environment it caused precipitation and adsorption reactions.

  7. Assessing the sustainability of acid mine drainage (AMD) treatment in South Africa.

    Science.gov (United States)

    Masindi, Vhahangwele; Chatzisymeon, Efthalia; Kortidis, Ioannis; Foteinis, Spyros

    2018-04-20

    The environmental sustainability of acid mine drainage (AMD) treatment at semi-industrial scale is examined by means of the life cycle assessment (LCA) methodology. An integrated process which includes magnesite, lime, soda ash and CO 2 bubbling treatment was employed to effectively treat, at semi-industrial scale, AMD originating from a coal mine in South Africa. Economic aspects are also discussed. AMD is a growing problem of emerging concern that cause detrimental effects to the environment and living organisms, including humans, and impose on development, health, access to clean water, thus also affect economic growth and cause social instability. Therefore, sustainable and cost effective treatment methods are required. A life cycle cost analysis (LCCA) revealed the viability of the system, since the levelized cost of AMD treatment can be as low as R112.78/m 3 (€7.60/m 3 or $9.35/m 3 ). Moreover, due to its versatility, the system can be used both at remote locales, at stand-alone mode (e.g. using solar energy), or can treat AMD at industrial scale, thus substantially improving community resilience at local and national level. In terms of environmental sustainability, 29.6 kg CO 2eq are emitted per treated m 3 AMD or its environmental footprint amount to 2.96 Pt/m 3 . South Africa's fossil-fuel depended energy mix and liquid CO 2 consumption were the main environmental hotspots. The total environmental footprint is reduced by 45% and 36% by using solar energy and gaseous CO 2 , respectively. Finally, AMD sludge valorisation, i.e. mineral recovery, can reduce the total environmental footprint by up to 12%. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara Brandi; Fuchs, Josefine

    2015-01-01

    PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included...... 1185 eyes in 1099 patients who began vascular endothelial growth factor inhibitor treatment for nAMD during four separate periods in 2007, 2009, 2011 and 2012 using a fixed loading-dose regimen of three ranibizumab injections. RESULTS: Mean best-corrected visual acuity (BCVA) at presentation remained....... CONCLUSION: In this study, 2-week-earlier injection was associated with the equivalent of a 5-Early Treatment Diabetic Retinopathy Study letter-gain in mean visual acuity at 3 months after presentation. The difference is larger than expected from the 2-week-longer duration of disease at the study end...

  9. Study progress of CCR3 in wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Xian-Wei Wu

    2014-03-01

    Full Text Available According to the study, chemokine receptor 3(CCR3in the eye is mainly distributed in retinal pigment epithelial cells, and also expressed in the choroidal vascular endothelial cells(CECs. The specificity of CCR3's high expression in wet age-related macular degeneration(AMDwas found, and it is proved that in wet-AMD patients, it plays an important role in the formation of choroidal neovascularization(CNV. In this paper, the structure, function, the problem of current research and the future direction of CCR3 were summarized. It is believed that with the further research on CCR3, it will not only help us to find a new method of wet-AMD diagnosis and treatment, but also may provide an important reference for other CNV disease research and new anti-CNV drugs.

  10. Are chronic myeloproliferative neoplasms associated with age-related macular degeneration?

    DEFF Research Database (Denmark)

    Bak, M.; Sorensen, T. L.; Flachs, E. M.

    2015-01-01

    population-based matched cohort study using Danish registries. We included all patients age 18+ or older with a first listed diagnosis of MPN in the Danish National Patient Registry between 1994 and 2013. Patients with Essential Thrombocythemia (ET), Polycythemia Vera (PV), Myelofibrosis (MF), Unclassifiable......Background. Patients with Chronic Myeloproliferative Neoplasms (MPNs) already have increased comorbidity at time of diagnosis, and studies show association with ophthalmic manifestations. Retinal vascular symptoms including vascular occlusions and hemorrhages are present, but other manifestations...... of the eye have not been thoroughly investigated in these patients. Previously reported studies show signs of systemic inflammation in patients with MPN as well as in patients with Age-Related Macular Degeneration (AMD). Our hypothesis is that the presence of MPN predisposes some individuals to develop AMD...

  11. Cataract surgery in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Kessel, Line; Theil, Pernille Koefoed; Sørensen, Torben Lykke

    2016-01-01

    Purpose To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice. Methods We extracted information about patients recorded...... in electronic databases managing anti-VEGF injections and cataract surgery. We compared Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and frequency of anti-VEGF injections before and after cataract surgery. Results We identified 89 eyes from 89 patients who had cataract surgery after being...... with an average of 1.5 in the 6 months before surgery versus 1.7 in the 6 months after surgery (p = 0.25). Visual improvement was greater in patients when the time from latest injection to cataract surgery was lower. Conclusions Cataract surgery improves vision in patients undergoing treatment for neovascular AMD...

  12. Kraepelin and degeneration theory.

    Science.gov (United States)

    Hoff, Paul

    2008-06-01

    Emil Kraepelin's contribution to the clinical and scientific field of psychiatry is recognized world-wide. In recent years, however, there have been a number of critical remarks on his acceptance of degeneration theory in particular and on his political opinion in general, which was said to have carried "overtones of proto-fascism" by Michael Shepherd [28]. The present paper discusses the theoretical cornerstones of Kraepelinian psychiatry with regard to their relevance for Kraepelin's attitude towards degeneration theory. This theory had gained wide influence not only in scientific, but also in philosophical and political circles in the last decades of the nineteenth century. There is no doubt that Kraepelin, on the one hand, accepted and implemented degeneration theory into the debate on etiology and pathogenesis of mental disorders. On the other hand, it is not appropriate to draw a simple and direct line from early versions of degeneration theory to the crimes of psychiatrists and politicians during the rule of national socialism. What we need, is a differentiated view, since this will be the only scientific one. Much research needs to be done here in the future, and such research will surely have a significant impact not only on the historical field, but also on the continuous debate about psychiatry, neuroscience and neurophilosophy.

  13. A novel fully automated molecular diagnostic system (AMDS for colorectal cancer mutation detection.

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    Shiro Kitano

    Full Text Available BACKGROUND: KRAS, BRAF and PIK3CA mutations are frequently observed in colorectal cancer (CRC. In particular, KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC. For mutation analysis, the current methods are time-consuming, and not readily available to all oncologists and pathologists. We have developed a novel, simple, sensitive and fully automated molecular diagnostic system (AMDS for point of care testing (POCT. Here we report the results of a comparison study between AMDS and direct sequencing (DS in the detection of KRAS, BRAF and PI3KCA somatic mutations. METHODOLOGY/PRINCIPAL FINDING: DNA was extracted from a slice of either frozen (n = 89 or formalin-fixed and paraffin-embedded (FFPE CRC tissue (n = 70, and then used for mutation analysis by AMDS and DS. All mutations (n = 41 among frozen and 27 among FFPE samples detected by DS were also successfully (100% detected by the AMDS. However, 8 frozen and 6 FFPE samples detected as wild-type in the DS analysis were shown as mutants in the AMDS analysis. By cloning-sequencing assays, these discordant samples were confirmed as true mutants. One sample had simultaneous "hot spot" mutations of KRAS and PIK3CA, and cloning assay comfirmed that E542K and E545K were not on the same allele. Genotyping call rates for DS were 100.0% (89/89 and 74.3% (52/70 in frozen and FFPE samples, respectively, for the first attempt; whereas that of AMDS was 100.0% for both sample sets. For automated DNA extraction and mutation detection by AMDS, frozen tissues (n = 41 were successfully detected all mutations within 70 minutes. CONCLUSIONS/SIGNIFICANCE: AMDS has superior sensitivity and accuracy over DS, and is much easier to execute than conventional labor intensive manual mutation analysis. AMDS has great potential for POCT equipment for mutation analysis.

  14. Modification of AMD wave functions and application to the breaking of the N=20 magic number

    International Nuclear Information System (INIS)

    Kimura, Masaaki; Horiuchi, Hisashi

    2001-01-01

    By using the deformed Gaussian instead of the spherical one, we have modified the AMD (Antisymmetrized Molecular Dynamics) wave functions. The calculation results with this modified AMD shows the drastic improvement of the deformation properties of Mg isotopes. This improvement means that this new version of AMD can treat the deformation of mean field properly than before and the deformation of mean field is important in Mg isotopes. With this new version of AMD, we have also calculated 32Mg in which the breaking of magic number N=20 is experimentally known. In this nucleus, β-energy surface is also drastically changed by the modification AMD wave function. Our results show that this nucleus is indeed deformed and neutron's 2p2h state is dominant in its ground state. This ground state reproduces the experimental data and shows the breaking of the magic number N=20 clearly. Additionally, near the ground state, there is also very interesting state which has neutron's 4p4h structure and shows parity violating density distribution and cluster-like nature. (author)

  15. Modification of AMD wave functions and application to the breaking of the N=20 magic number

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Masaaki; Horiuchi, Hisashi [Kyoto Univ. (Japan). Dept. of Physics

    2001-09-01

    By using the deformed Gaussian instead of the spherical one, we have modified the AMD (Antisymmetrized Molecular Dynamics) wave functions. The calculation results with this modified AMD shows the drastic improvement of the deformation properties of Mg isotopes. This improvement means that this new version of AMD can treat the deformation of mean field properly than before and the deformation of mean field is important in Mg isotopes. With this new version of AMD, we have also calculated 32Mg in which the breaking of magic number N=20 is experimentally known. In this nucleus, {beta}-energy surface is also drastically changed by the modification AMD wave function. Our results show that this nucleus is indeed deformed and neutron's 2p2h state is dominant in its ground state. This ground state reproduces the experimental data and shows the breaking of the magic number N=20 clearly. Additionally, near the ground state, there is also very interesting state which has neutron's 4p4h structure and shows parity violating density distribution and cluster-like nature. (author)

  16. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ayako; Honda, Kaoru; Ishibashi, Tatsuro; Shioyama, Yoshiyuki [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1998-11-01

    We evaluated the effects of low-dose radiation on choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Since Chakravarthy reported the benefits from administration of low-dose external-beam irradiation for CNV, many studies have demonstrated that irradiation could have a beneficial treatment effect, whereas several reports have not. In our hospital, 12 eyes with AMD received 10 Gy of 4 MV photons and the other 9 eyes received 20 Gy. Another 4 eyes were untreated as control. After 6 months of treatment, visual acuity was maintained in 11 eyes, improved in 5 eyes, and deteriorated in 5 eyes of treated patients. In control group, visual acuity was maintained in 1 eye and deteriorated in 3 eyes. The size of CNV regressed in 10 eyes, remained stationary in 2 eyes and progressed in 2 eyes of treated patients, while in control group CNV regressed in 2 eyes and remained stationary in 1 eye. After 12 months some CNV progressed. Although the present result seems to be better than those in previous reports, whether or not the treatment is beneficial has to be awaited. (author)

  17. Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

    Science.gov (United States)

    Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

    2012-10-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

  18. Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper

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    Miguel Hage Amaro

    2012-12-01

    Full Text Available PURPOSE: To report the response of choroidal neovascularization (CNV to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD with extensive pre-existing geographic atrophy (GA and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF agent (ranibizumab for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti

  19. ISSLS Prize winner: Long-term follow-up suggests spinal fusion is associated with increased adjacent segment disc degeneration but without influence on clinical outcome: results of a combined follow-up from 4 randomized controlled trials.

    Science.gov (United States)

    Mannion, Anne F; Leivseth, Gunnar; Brox, Jens-Ivar; Fritzell, Peter; Hägg, Olle; Fairbank, Jeremy C T

    2014-08-01

    Cross-sectional analysis of long-term follow-up (LTFU) data from 4 randomized controlled trials of operative versus nonoperative treatment for chronic low back pain. To examine the influence of spinal fusion on adjacent segment disc space height as an indicator of disc degeneration at LTFU. There is ongoing debate as to whether adjacent segment disc degeneration results from the increased mechanical stress of fusion. Plain standing lateral radiographs were obtained at LTFU (mean, 13 ± 4 yr postrandomization) in 229 of 464 (49%) patients randomized to surgery and 140 of 303 (46%), to nonoperative care. Disc space height and posteroanterior displacement were measured for each lumbar segment using a validated computer-assisted distortion compensated roentgen analysis technique. Values were reported in units of standard deviations above or below age and sex-adjusted normal values. Patient-rated outcomes included the Oswestry Disability Index and pain scales. Radiographs were usable in 355 of 369 (96%) patients (259 fusion and 96 nonoperative treatment). Both treatment groups showed significantly lower values for disc space height of the adjacent segment than norm values. There was a significant difference between treatment groups for the disc space height of the cranial adjacent segment (in both as-treated and intention-to-treat analyses). The mean treatment effect of fusion on adjacent segment disc space height was -0.44 SDs (95% CI, -0.77 to -0.11; P = 0.01; as-treated analysis); there was no group difference for posteroanterior displacement (0.18 SDs, 95% confidence interval, -0.28 to 0.64, P = 0.45). Adjacent level disc space height and posteroanterior displacement were not correlated with Oswestry Disability Index or pain scores at LTFU (r = 0.010-0.05; P > 0.33). Fusion was associated with lower disc space height at the adjacent segment after an average of 13 years of FU. The reduced disc space height had no influence on patient self-rated outcomes (pain or

  20. Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration

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    Keles S

    2014-08-01

    Full Text Available Sadullah Keles,1 Orhan Ates,1 Baki Kartal,2 Hamit Hakan Alp,3 Metin Ekinci,4 Erdinc Ceylan,2 Osman Ondas,5 Eren Arpali,2 Semih Dogan,6 Kenan Yildirim,7 Mevlut Sait Keles8 1Department of Ophthalmology, School of Medicine, Ataturk University, Erzurum, Turkey; 2Department of Ophthalmology, Regional Training and Research Hospital, Erzurum, Turkey; 3Department of Biochemistry, School of Medicine, Yuzuncu Yil University, Van, Turkey; 4Department of Ophthalmology, School of Medicine, Kafkas University, Kars, Turkey; 5Department of Ophthalmology, Erbaa Government Hospital, Tokat, Turkey; 6Department of Ophthalmology, Kolan Hospital, Istanbul, Turkey; 7Department of Ophthalmology, Igdir Government Hospital, Igdir, Turkey; 8Department of Biochemistry, School of Medicine, Ataturk University, Erzurum, Turkey Aim: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA, and nitric oxide (NO, as well as activity of endothelial NO synthase (eNOS, in patients with age-related macular degeneration (AMD.Methods: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30 were compared to a control group with no retinal pathology (n=30.Results: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001, whereas NO levels and eNOS activity were higher in the control group (P<0.001. In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively.Conclusion: Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD. Keywords: age-related macular

  1. Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

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    Zhu W

    2017-10-01

    Full Text Available Wei Zhu,1,* Yi-Fang Meng,1,* Qian Xing,1 Jian-Jun Tao,1 Jiong Lu,1 Yan Wu2 1Department of Ophthalmology, Changshu No. 2 People’s Hospital, Changshu, China; 2Department of Ophthalmology, First Hospital Affiliated to Soochow University, Suzhou, China *These authors contributed equally to this work Background: Age-related macular degeneration (AMD is one of the most common causes of adult blindness in developed countries. However, the role of long noncoding RNAs (lncRNAs in the development and progression of early AMD is unclear.Methods: We established the lncRNA profile of early AMD by reannotation of microarrays from the gene expression omnibus database. Quantitative real-time polymerase chain reaction was used to determine the expression of selected lncRNAs.Results: The expression profiles of 9 cases of AMD and 7 controls were studied. A total of 266 differentially expressed genes (DEGs were detected (94 upregulated and 172 downregulated. Among all the DEGs, 64 were lncRNAs. Advanced bioinformatics analyses demonstrated that differentially expressed lncRNAs could play significant roles in visual perception, sensory perception of light stimulus, and cognition. The pathway analyses showed that the two most significantly influenced Kyoto Encyclopedia of Genes and Genomes pathways were those of phototransduction and purine metabolism. By the analyses of the key lncRNAs, it was found that RP11-234O6.2 was downregulated in the aging retinal pigment epithelium (RPE cellular model. Exogenous RP11-234O6.2 treatment led to increased cell viability and improved apoptosis but it did not affect the cell migration ability of aging RPE cells.Conclusion: This study indicated that lncRNAs are differentially expressed in early AMD and may produce important regulative effects. An lncRNA, RP11-234O6.2, might be involved in the biological regulation of early AMD and have therapeutic potential. Keywords: age-related macular degeneration, lncRNAs, microarray

  2. An in silico model of retinal cholesterol dynamics (RCD model): insights into the pathophysiology of dry AMD[S

    Science.gov (United States)

    Zekavat, Seyedeh Maryam; Lu, James; Maugeais, Cyrille; Mazer, Norman A.

    2017-01-01

    We developed an in silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry age-related macular degeneration. Based on existing experimental data and mechanistic hypotheses, we estimated the Ch turnover rate in the ROS to be 1–6 pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and found comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to the outer retina, ABCA1-mediated Ch efflux from the RPE to the choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE. The drusen growth rate is predicted to increase from 0.7 to 4.2 μm/year in proportion to the flux of ApoB-Ch particles. The rapid regression of drusen may be explained by macrophage-mediated clearance if the macrophage density reaches ∼3,500 cells/mm2. The RCD model quantifies retinal Ch dynamics and suggests that retinal Ch turnover and recycling, ApoB-Ch particle efflux, and macrophage-mediated clearance may explain the dynamics of drusen growth and regression. PMID:28442497

  3. R102G polymorphism of the complement component 3 gene in Malaysian subjects with neovascular age-related macular degeneration

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    Nur Afiqah Mohamad

    2018-04-01

    Full Text Available Background: Genetic and environmental factors are known to be risk factors in development of neovascular age-related macular degeneration (nAMD. Genetic factors such as polymorphisms in the complement component pathway genes might play a role in pathogenesis of nAMD and has been studied in various populations excluding Malaysia. Aim of the study: To determine the association of the R102G polymorphism of the complement component (C3 gene in nAMD subjects. Patients and methods: A total of 301 Malaysian subjects (149 case and 152 controls were recruited and genotyped for the R102G (rs2230199 variant of the C3 gene. Genotyping was conducted using the PCR-RFLP method and association analysis was conducted using appropriate statistical tests. Results: From our findings, no significant association was observed in the allele distribution of C3 R102G between nAMD and controls (OR = 1.42, 95% CI = 0.77–2.62, P = 0.268. A further analysis that compared three genetic models (dominant, recessive and co-dominant also recorded no significant difference (P > 0.05. These findings could be due to the low frequency of the GG variant in the case (4.7% and control (1.3% groups, compared to the normal variant CC, which is present in 91.3% of case and 92.8% of control alleles. Conclusion: The present study showed no evidence of association between C3 R102G polymorphism and nAMD in Malaysian subjects. Keywords: Age-related macular degeneration, Complement component 3, C3 gene, R102G gene polymorphism

  4. Fault Diagnosis of Rotating Machinery Based on Adaptive Stochastic Resonance and AMD-EEMD

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    Peiming Shi

    2016-01-01

    Full Text Available An adaptive stochastic resonance and analytical mode decomposition-ensemble empirical mode decomposition (AMD-EEMD method is proposed for fault diagnosis of rotating machinery in this paper. Firstly, the stochastic resonance system is optimized by particle swarm optimization (PSO, and the best structure parameters are obtained. Then, the signal with noise is put into the stochastic resonance system and denoising and enhancing the signal. Secondly, the signal output from the stochastic resonance system is extracted by analytical mode decomposition (AMD method. Finally, the signal is decomposed by ensemble empirical mode decomposition (EEMD method. The simulation results show that the optimal stochastic resonance system can effectively improve the signal-to-noise ratio, and the number of effective components of EEMD decomposition is significantly reduced after using AMD, thus improving the decomposition results of EEMD and enhancing the amplitude of components frequency. Through the extraction of the rolling bearing fault signal feature proved that the method has a good effect.

  5. Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study

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    Kenney M Cristina

    2013-01-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924 and CFH (T > C; Try402His, rs1061170. Methods Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. Results The JTU haplogroup cluster occurred in 34% (55/162 of AMD subjects versus 15% (24/164 of normal (OR = 2.99; p = 0.0001. This association was slightly greater in males (OR = 3.98, p = 0.005 than the female population (OR = 3.02, p = 0.001. Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001 and CFH (rs1061170; p = 0.027 SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924 or CFH (rs1061170 SNPs on the JTU haplogroup background. Conclusions There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924 and CFH (rs1061170 genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.

  6. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi......Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP...... and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...

  7. Adjacent segment degeneration

    OpenAIRE

    Birjandi, Alireza

    2012-01-01

    Abstract: Adjacent segment disease (ASD) is defined as degeneration that develops at mobile segments above or below a fused spinal segment and usually develops after spinal fusion or other back surgeries. Nearly 5 decades ago, the medical findings related to ASD were usually released in case reports as a relatively unusual complication of lumbar or lumbosacral fusions. Since the initial reports, ASD has been found to occur more often than the earlier predictions for its prospect incidence. It...

  8. Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration

    Science.gov (United States)

    Ratnapriya, Rinki; Zhan, Xiaowei; Fariss, Robert N.; Branham, Kari E.; Zipprer, David; Chakarova, Christina F.; Sergeev, Yuri V.; Campos, Maria M.; Othman, Mohammad; Friedman, James S.; Maminishkis, Arvydas; Waseem, Naushin H.; Brooks, Matthew; Rajasimha, Harsha K.; Edwards, Albert O.; Lotery, Andrew; Klein, Barbara E.; Truitt, Barbara J.; Li, Bingshan; Schaumberg, Debra A.; Morgan, Denise J.; Morrison, Margaux A.; Souied, Eric; Tsironi, Evangelia E.; Grassmann, Felix; Fishman, Gerald A.; Silvestri, Giuliana; Scholl, Hendrik P.N.; Kim, Ivana K.; Ramke, Jacqueline; Tuo, Jingsheng; Merriam, Joanna E.; Merriam, John C.; Park, Kyu Hyung; Olson, Lana M.; Farrer, Lindsay A.; Johnson, Matthew P.; Peachey, Neal S.; Lathrop, Mark; Baron, Robert V.; Igo, Robert P.; Klein, Ronald; Hagstrom, Stephanie A.; Kamatani, Yoichiro; Martin, Tammy M.; Jiang, Yingda; Conley, Yvette; Sahel, Jose-Alan; Zack, Donald J.; Chan, Chi-Chao; Pericak-Vance, Margaret A.; Jacobson, Samuel G.; Gorin, Michael B.; Klein, Michael L.; Allikmets, Rando; Iyengar, Sudha K.; Weber, Bernhard H.; Haines, Jonathan L.; Léveillard, Thierry; Deangelis, Margaret M.; Stambolian, Dwight; Weeks, Daniel E.; Bhattacharya, Shomi S.; Chew, Emily Y.; Heckenlively, John R.; Abecasis, Gonçalo R.; Swaroop, Anand

    2014-01-01

    Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch′s membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 × 10−5). Thus, it appears that rare and common variants in a single gene—FBN2—can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch′s membrane in maintaining blood–retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes. PMID:24899048

  9. Expression analysis of an evolutionarily conserved alternative splicing factor, Sfrs10, in age-related macular degeneration.

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    Devi Krishna Priya Karunakaran

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness in the elderly population. Hypoxic stress created in the micro-environment of the photoreceptors is thought to be the underlying cause that results in the pathophysiology of AMD. However, association of AMD with alternative splicing mediated gene regulation is not well explored. Alternative Splicing is one of the primary mechanisms in humans by which fewer protein coding genes are able to generate a vast proteome. Here, we investigated the expression of a known stress response gene and an alternative splicing factor called Serine-Arginine rich splicing factor 10 (Sfrs10. Sfrs10 is a member of the serine-arginine (SR rich protein family and is 100% identical at the amino acid level in most mammals. Immunoblot analysis on retinal extracts from mouse, rat, and chicken showed a single immunoreactive band. Further, immunohistochemistry on adult mouse, rat and chicken retinae showed pan-retinal expression. However, SFRS10 was not detected in normal human retina but was observed as distinct nuclear speckles in AMD retinae. This is in agreement with previous reports that show Sfrs10 to be a stress response gene, which is upregulated under hypoxia. The difference in the expression of Sfrs10 between humans and lower mammals and the upregulation of SFRS10 in AMD is further reflected in the divergence of the promoter sequence between these species. Finally, SFRS10+ speckles were independent of the SC35+ SR protein speckles or the HSF1+ stress granules. In all, our data suggests that SFRS10 is upregulated and forms distinct stress-induced speckles and might be involved in AS of stress response genes in AMD.

  10. Influence of age-related macular degeneration on macular thickness measurement made with fourier-domain optical coherence tomography.

    Science.gov (United States)

    Garas, Anita; Papp, András; Holló, Gábor

    2013-03-01

    To evaluate the influence of age-related macular degeneration (AMD) on macular thickness measurement made with Fourier-domain optical coherence tomography (RTVue-OCT) to detect glaucoma. : One nonglaucomatous eye of 79 white persons was imaged. This comprised 25 healthy eyes, 19 eyes with early/intermediate AMD (geographic atrophy excluded), 16 eyes with subfoveal choroidal neovascularization (CNV), and 19 CNV eyes after intravitreal antiangiogenic treatment [CNV-antivascular endothelial growth factor (VEGF)]. Compared with the age-matched controls, no difference in any nerve fiber layer and optic disc parameter was seen for any AMD group. No macular retinal segmentation error was detected in the control group. Localized inner retinal image segmentation errors topographically related to AMD were detected in 8 eyes with drusen (42.1%), all 16 CNV eyes (100%) and 17 eyes in the CNV-anti-VEGF group (89.5%; χ test, P0.05). In contrast, all pattern-based ganglion cell complex (GCC) parameters were significantly higher (more abnormal) in the CNV and CNV-anti-VEGF group than in the control eyes (Mann-Whitney test, Bonferroni correction, P<0.001). For GCC focal loss volume, the only pattern-based parameter classified by the software, the frequency of "borderline" and "outside normal limits" classifications was significantly greater in each AMD group than in the control group (χ test, Bonferroni correction, P ≤0.03). In nonglaucomatous eyes, AMD significantly influences the pattern-based inner macular thickness parameters of the RTVue optical coherence tomograph and the software-provided classification of GCC focal loss volume, for detection of glaucoma.

  11. Effect of Complement Factor B Gene Polymorphisms on Age-Related Macular Degeneration in North-East of Iran Population

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    N. Roshani Pour

    2017-09-01

    Full Text Available Aims: Age-related macular degeneration (AMD is the most prevalent cause of irreversible blindness and debilitating in old stages, in developed and developing countries that engage the central part of the retina or macula. The aim of this study was to evaluate the relationship of the rs4151667 position of the complement factor B gene polymorphism with AMD (dry type with geographic atrophy phenotype in the North East of Iran population. ­Materials & Methods:­ In this descriptive cross-sectional study in 2015-2016, 44 AMD patients (dry type with geographic atrophy phenotype were randomly selected from Gonabad City, Iran, health centers as the patient group. 50 healthy individuals from the same society that have no relative relations with each other or the patients, but were adapted by age and sex to the patient group, were selected as the control group. The ­­polymorphism of rs4151667 (c.26T>A­ position of the complement factor B gene was determined for all samples by Restriction Fragment Length Polymorphism (RFLP. Data was analyzed the Chi-square test in 2x2.Contingency software. Findings: The frequency of TT genotype in AMD patients (95.5% was significantly (p=0.048 more than the control group (88.0%, but the frequency of AT genotype in AMD patients (4.5% was significantly (p=0.025 less than the control group (12.0%. Conclusion: The polymorphism of rs4151667 (c.26T>A position of complement factor B is effective on the development of AMD in North East of Iran population.

  12. Joint Effect of CFH and ARMS2/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population

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    Kai Fang

    2015-01-01

    Full Text Available Purpose. The etiology of neovascular age-related macular degeneration (nAMD cannot be completely explained by identified environmental risk factors or single-locus gene variants. This study was to explore the potential interactions among gene variants on nAMD in Chinese population. Methods. 43 SNPs located in different genes were genotyped in 932 Chinese individuals (464 nAMD patients and 468 controls. We explored the potential interactions among gene variants using generalized multifactor dimensionality reduction (GMDR algorithm and the method to measure the departure from the additivity model. Results. The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001 with the highest cross-validation consistency (10/10 and the best testing balanced accuracy (64.50%. In addition, based on the method to measure the departure from the additivity model, the synergy index (S was 2.63 (1.09–6.38 and the attributable proportion due to interaction (AP was 55.7% (21.4%–89.9%, which suggested that a common pathway may exist for these genes for nAMD. Those who carried CC for rs3793917 and TC/CC for rs1061170 were at the highest risk of nAMD (OR: 9.76, 95% CI: 4.65–20.51. Conclusions. Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained.

  13. Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration

    Science.gov (United States)

    Baas, Dominique C.; Ho, Lintje; Tanck, Michael W.T.; Fritsche, Lars G.; Merriam, Joanna E.; van het Slot, Ruben; Koeleman, Bobby P.C.; Gorgels, Theo G.M.F.; van Duijn, Cornelia M.; Uitterlinden, André G.; de Jong, Paulus T.V.M.; Hofman, Albert; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C.W.; Dean, Michael; Weber, Bernhard H. F.; Allikmets, Rando; Hageman, Gregory S.

    2012-01-01

    Purpose Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress–mediated AMD pathology. Methods Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed. Results In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies. Conclusions No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists. PMID:22509097

  14. Interleukin-13 and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Bo Fu

    2017-04-01

    Full Text Available AIM: To identify the effects of interleukin (IL-13 on retinal pigment epithelial (RPE cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA. ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α, transforming growth factor-β (TGF-β and vascular endothelial growth factor (VEGF were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01. In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001 and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001 after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008. IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005 at 48h, but the level of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004 and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001. While expressions of VEGF didn’t change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

  15. Behavior of the Age Related Macular Degeneration in Sancti Spiritus province.

    OpenAIRE

    Yanelis Emilia Tabio Henry; Miriam Rodríguez Rodríguez; Esther Gómez Guzmán

    2011-01-01

    The age-related macular degeneration (ARMD) is a bilateral maculopathy that affect central vision and has a social, scientific and economic repercussion due to the visual discapacity that causes.With the objective of characterizing the behaviour of the AMD, it was done a study of 49 patients that went to the retina consultation of the oftalmological service from the General Hospital Camilo Cienfuegos of Sancti Spíritus the period of january 1 st , 2006 to december 31 st 2008. Different var...

  16. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  17. [Volumetric analysis of vascularized pigment epithelium detachment in AMD: post hoc analysis of the RECOVER study].

    Science.gov (United States)

    Clemens, C R; Alten, F; Heiduschka, P; Gamulescu, M A; Wolf, A; Eter, N

    2017-10-20

    The ratio of choroidal neovascularization (CNV) and pigment epithelium detachment (PED) represents an important parameter regarding the risk of developing a tear of the retinal pigment epithelium (RPE) in patients with vascularized PED due to age-related macular degeneration (AMD). Within the framework of the RECOVER study a total of 29 treatment-naive patients with vascularized PED underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) volume scans. The CNV-PED ratio was evaluated retrospectively by two independent graders in three ways: 1) manually based on the en face image of the FA late phase and 2) manually based on the en face image of the ICGA late phase. 3) In every OCT scan encompassing the PED, the area between the RPE and Bruch's membrane and the CNV area was measured and multiplied by the distance between OCT scans in order to determine volumetric data of CNV, PED and the serous cavity. The FA and ICGA showed a mean serous area of 6.14 ± 4.21 mm 2 (ICGA 5.94 ± 4.13 mm 2 ), a mean CNV area of 3.25 ± 1.79 mm 2 (ICGA 2.84 ± 1.68 mm 2 ) and a mean PED area of 9.39 ± 4.27 mm 2 (ICGA 8.79 ± 4.23 mm 2 ) resulting in a mean two-dimensional morphological ratio of 0.35 ± 0.21 (ICGA 0.32 ± 0.22). The volumetric measurement revealed a mean CNV volume of 0.63 ± 0.67 mm 3 , a mean serous volume of 3.61 ± 3.83 mm 3 and a mean total PED volume of 4.25 ± 3.68 mm 3 . The mean three-dimensional morphological ratio was 0.15 ± 0.29. The difference between the two-dimensional ratios of FA (p < 0.0001) and ICGA (p = 0.0004) was significant compared to the three-dimensional OCT ratio. Assessment of the CNV-PED ratio using volumetric OCT measurements is an additional tool to the en face modalities FA and ICGA. This seems to be clinically relevant regarding the risk stratification of RPE tear development in PED patients and for the planning of the treatment regimen.

  18. Automated Grading of Age-Related Macular Degeneration From Color Fundus Images Using Deep Convolutional Neural Networks.

    Science.gov (United States)

    Burlina, Philippe M; Joshi, Neil; Pekala, Michael; Pacheco, Katia D; Freund, David E; Bressler, Neil M

    2017-11-01

    Age-related macular degeneration (AMD) affects millions of people throughout the world. The intermediate stage may go undetected, as it typically is asymptomatic. However, the preferred practice patterns for AMD recommend identifying individuals with this stage of the disease to educate how to monitor for the early detection of the choroidal neovascular stage before substantial vision loss has occurred and to consider dietary supplements that might reduce the risk of the disease progressing from the intermediate to the advanced stage. Identification, though, can be time-intensive and requires expertly trained individuals. To develop methods for automatically detecting AMD from fundus images using a novel application of deep learning methods to the automated assessment of these images and to leverage artificial intelligence advances. Deep convolutional neural networks that are explicitly trained for performing automated AMD grading were compared with an alternate deep learning method that used transfer learning and universal features and with a trained clinical grader. Age-related macular degeneration automated detection was applied to a 2-class classification problem in which the task was to distinguish the disease-free/early stages from the referable intermediate/advanced stages. Using several experiments that entailed different data partitioning, the performance of the machine algorithms and human graders in evaluating over 130 000 images that were deidentified with respect to age, sex, and race/ethnicity from 4613 patients against a gold standard included in the National Institutes of Health Age-related Eye Disease Study data set was evaluated. Accuracy, receiver operating characteristics and area under the curve, and kappa score. The deep convolutional neural network method yielded accuracy (SD) that ranged between 88.4% (0.5%) and 91.6% (0.1%), the area under the receiver operating characteristic curve was between 0.94 and 0.96, and kappa coefficient (SD

  19. Secondary iron minerals present in AMD sediments from Smolník abandoned mine

    Czech Academy of Sciences Publication Activity Database

    Dakos, Z.; Ku