Distinguishing wet from dry age-related macular degeneration using three-dimensional computer-automated threshold Amsler grid testing

Background/aims: With the increased efficacy of current therapy for wet age-related macular degeneration (AMD), better ways to detect wet AMD are needed. This study was designed to test the ability of three-dimensional contrast threshold Amsler grid (3D-CTAG) testing to distinguish wet AMD from dry AMD. Methods: Conventional paper Amsler grid and 3D-CTAG tests were performed in 90 eyes: 63 with AMD (34 dry, 29 wet) and 27 controls. Qualitative comparisons were based upon the three-dimensional shapes of central visual field (VF) defects. Quantitative analyses considered the number and volume of the three-dimensional defects. Results: 25/34 (74%) dry AMD and 6/29 (21%) wet AMD eyes had no distortions on paper Amsler grid. Of these, 5/25 (20%) dry and 6/6 (100%) wet (p=0.03) AMD eyes exhibited central VF defects with 3D-CTAG. Wet AMD displayed stepped defects in 16/28 (57%) eyes, compared with only 2/34 (6%) of dry AMD eyes (p=0.002). All three volumetric indices of VF defects were two- to four-fold greater in wet than dry AMD (p<0.006). 3D-CTAG had 83.9% positive and 90.6% negative predictive values for wet AMD. Conclusions: 3D-CTAG has a higher likelihood of detecting central VF defects than conventional Amsler grid, especially in wet AMD. Wet AMD can be distinguished from dry AMD by qualitative and quantitative 3D-CTAG criteria. Thus, 3D-CTAG may be useful in screening for wet AMD, quantitating disease severity, and providing a quantitative outcome measure of therapy

AMD-stability and the classification of planetary systems

We present here in full detail the evolution of the angular momentum deficit (AMD) during collisions as it was described in (Laskar, PRL,2000). Since then, the AMD has been revealed to be a key parameter for the understanding of the outcome of planetary formation models. We define here the AMD-stability criterion that can be easily verified on a newly discovered planetary system. We show how AMD-stability can be used to establish a classification of the multiplanet systems in order to exhibit the planetary systems that are long-term stable because they are AMD-stable, and those that are AMD-unstable which then require some additional dynamical studies to conclude on their stability. The AMD-stability classification is applied to the 131 multiplanet systems from The Extrasolar Planet Encyclopaedia database (exoplanet.eu) for which the orbital elements are sufficiently well known.Comment: 18 pages, 13 figures, A&A in pres

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

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

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 treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD

Cost effectiveness of treatments for wet age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in people aged >= 50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination and Cochrane Library databases were searched for all wet AMD health technology assessments (HTAs). Overall, 44 publications were evaluated in full and included in this review. A broad range of cost-effectiveness analyses were identified for the most commonly used therapies for wet AMD (pegaptanib, ranibizumab and photodynamic therapy [PDT] with verteporfin). Three studies evaluated the cost effectiveness of bevacizumab in wet AMD. A small number of analyses of other treatments, such as laser photocoagulation and antioxidant vitamins, were also found. Ranibizumab was consistently shown to be cost effective for wet AMD in comparison with all the approved wet AMD therapies (four of the five studies identified showed ranibizumab was cost effective vs usual care, PDT or pegaptanib); however, there was considerable variation in the methodology for cost-effectiveness modelling between studies. Findings from the HTAs supported those from the PubMed and EM BASE searches; of the seven HTAs that included ranibizumab, six (including HTAs for Australia, Canada and the UK) concluded that ranibizumab was cost effective for the treatment of wet AMD; most compared ranibizumab with PDT and/or pegaptanib. By contrast, HTAs at best generally recommended pegaptanib or PDT for restricted use in subsets of patients with wet AMD. In the literature analyses, pegaptanib was found to be cost effective versus usual/best supportive care (including PDT) or no treatment in one of five studies; the other four studies found pegaptanib was of borderline cost effectiveness depending on the stage of disease and time horizon. PDT was shown to be cost effective versus usual/best supportive care or no treatment in five of nine studies; two studies showed that PDT was of borderline cost effectiveness depending on baseline visual acuity, and two showed that PDT was not cost effective. We identified no robust studies that properly evaluated the cost effectiveness of bevacizumab in wet AMD

The estimated prevalence and incidence of late stage age related macular degeneration in the UK

BACKGROUND: UK estimates of age related macular degeneration (AMD) occurrence vary. AIMS: To estimate prevalence, number and incidence of AMD by type in the UK population aged ≥50 years. METHODS: Age-specific prevalence rates of AMD obtained from a Bayesian meta-analysis of AMD prevalence were applied to UK 2007-2009 population data. Incidence was estimated from modelled age-specific prevalence. RESULTS: Overall prevalence of late AMD was 2.4% (95% credible interval (CrI) 1.7% to 3.3%), equivalent to 513 000 cases (95% CrI 363 000 to 699 000); estimated to increase to 679 000 cases by 2020. Prevalences were 4.8% aged ≥65 years, 12.2% aged ≥80 years. Geographical atrophy (GA) prevalence rates were 1.3% (95% CrI 0.9% to 1.9%), 2.6% (95% CrI 1.8% to 3.7%) and 6.7% (95% CrI 4.6% to 9.6%); neovascular AMD (NVAMD) 1.2% (95% CrI 0.9% to 1.7%), 2.5% (95% CrI 1.8% to 3.4%) and 6.3% (95% CrI 4.5% to 8.6%), respectively. The estimated number of prevalent cases of late AMD were 60% higher in women versus men (314 000 cases in women, 192 000 men). Annual incidence of late AMD, GA and NVAMD per 1000 women was 4.1 (95% CrI 2.4% to 6.8%), 2.4 (95% CrI 1.5% to 3.9%) and 2.3 (95% CrI 1.4% to 4.0%); in men 2.6 (95% CrI 1.5% to 4.4%), 1.7 (95% CrI 1.0% to 2.8%) and 1.4 (95% CrI 0.8% to 2.4%), respectively. 71 000 new cases of late AMD were estimated per year. CONCLUSIONS: These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments

Antisymmetrized molecular dynamics of wave packets with stochastic incorporation of Vlasov equation

On the basis of the antisymmetrized molecular dynamics (AMD) of wave packets for the quantum system, a novel model (called AMD-V) is constructed by the stochastic incorporation of the diffusion and the deformation of wave packets which is calculated by Vlasov equation without any restriction on the one-body distribution. In other words, the stochastic branching process in molecular dynamics is formulated so that the instantaneous time evolution of the averaged one-body distribution is essentially equivalent to the solution of Vlasov equation. Furthermore, as usual molecular dynamics, AMD-V keeps the many-body correlation and can naturally describe the fluctuation among many channels of the reaction. It is demonstrated that the newly introduced process of AMD-V has drastic effects in heavy ion collisions of 40Ca + 40Ca at 35 MeV/nucleon, especially on the fragmentation mechanism, and AMD-V reproduces the fragmentation data very well. Discussions are given on the interrelation among the frameworks of AMD, AMD-V and other microscopic models developed for the nuclear dynamics.Comment: 26 pages, LaTeX with revtex and epsf, embedded postscript figure