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Sample records for macular degeneration amd

  1. [Age-related macular degeneration (AMD)].

    PubMed

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  2. Genetic risk factors and age-related macular degeneration (AMD)

    PubMed Central

    Mousavi, Maryam; Armstrong, Richard A.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available.

  3. New Treatment Greatly Improves Prognosis for Patients with AMD (Age-Related Macular Degeneration)

    MedlinePlus

    ... turn JavaScript on. Feature: Age-related Macular Degeneration New Treatment Greatly Improves Prognosis for Patients with AMD ... Eye Institute Photo Courtesy of: NEI In a new study of nearly 650 people with age-related ...

  4. Protect Your Eyes: Age-Related Macular Degeneration (AMD) Facts and Prevention Tips

    MedlinePlus

    PROTECT YOUR EYES Age-Related Macular Degeneration ( AMD ) FACTS & PREVENTION TIPS A LEADING CAUSE OF VISION LOSS IN THE U.S . AMD is a ... Black 2% Other 89% White As the population ages, the number of cases is expected to increase ...

  5. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  6. Macular Degeneration Partnership

    MedlinePlus

    ... Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To raise awareness of AMD, the Macular Degeneration Partnership (MDP) is distributing a public service announcement (PSA) nationwide. Seen through the eyes of a ...

  7. The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

    PubMed Central

    Wang, Y; Wang, V M; Chan, C-C

    2011-01-01

    Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. PMID:21183941

  8. SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

    PubMed

    Enseleit, Frank; Michels, Stephan; Sudano, Isabella; Stahel, Marc; Zweifel, Sandrine; Schlager, Oliver; Becker, Matthias; Winnik, Stephan; Nägele, Matthias; Flammer, Andreas J; Neidhart, Michel; Graf, Nicole; Matter, Christian M; Seifert, Burkhardt; Lüscher, Thomas F; Ruschitzka, Frank

    2017-09-02

    To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD). In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizumab 1.25 mg at 4-week intervals and were subsequently followed every 4 weeks and treated according to a pro re nata regime for up to 1 year. Patients with dry AMD served as controls. The primary endpoint was the change in EF assessed by flow-mediated dilatation (FMD) after 2 months of treatment with VEGF inhibitors in patients with AMD compared to patients with dry AMD. FMD was assessed with B-mode high-resolution ultrasonography of the left brachial artery. 24 patients with neovascular AMD and 26 patients with dry ADM were included in the trial. Treatment with VEGF inhibitors did not significantly change FMD (from 4.7 ± 2.4 to 3.9 ± 1.9% after 8 weeks, p = 0.07, and to 5.1 ± 2.0% after 1 year; p = 0.93 vs. baseline, respectively). EF did not significantly differ between patients with neovascular AMD treated with intravitreal VEGF inhibition and patients with dry AMD. © 2017 S. Karger AG, Basel.

  9. Overview of Risk Factors for Age-Related Macular Degeneration (AMD).

    PubMed

    Armstrong, Richard A; Mousavi, Maryam

    2015-01-01

    Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make life style choices that may reduce the risk of disease. This review discusses the role of genetics, sunlight, diet, cardiovascular factors, smoking, and alcohol as possible risk factors for AMD. Genetics plays a more significant role in AMD than previously thought, especially in younger patients, histocompatibility locus antigen (HLA) and complement system genes being the most significant. Whether the risk of AMD is increased by exposure to sunlight, cardiovascular risk factors, and diet is more controversial. Smoking is the risk factor most consistently associated with AMD. Current smokers are exposed to a two to three times higher risk of AMD than non-smokers and the risk increases with intensity of smoking. Moderate alcohol consumption is unlikely to increase the risk of AMD. Optometrists as front-line informers and educators of ocular health play a significant role in increasing public awareness of the risks of AMD. Cessation of smoking, the use of eye protection in high light conditions, dietary changes, and regular use of dietary supplements should all be considered to reduce the lifetime risk of AMD.

  10. The genetics of age-related macular degeneration (AMD)--Novel targets for designing treatment options?

    PubMed

    Grassmann, Felix; Fauser, Sascha; Weber, Bernhard H F

    2015-09-01

    Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs.

  11. Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy

    PubMed Central

    Martins, Ana Sofia; Gil, João; Miller, John B.; Marques, Marco; Mesquita, Tânia; Kim, Ivana K.; Cachulo, Maria da Luz; Vavvas, Demetrios; Carreira, Isabel M.; Murta, Joaquim N.; Silva, Rufino; Miller, Joan W.; Husain, Deeba

    2017-01-01

    Purpose To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. Methods Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. Results Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. Conclusion For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted. PMID:28542375

  12. Retinal Ultrastructure of Murine Models of Dry Age-related Macular Degeneration (AMD)

    PubMed Central

    Ramkumar, Hema L.; Zhang, Jun; Chan, Chi-Chao

    2010-01-01

    Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch’s membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr−/− (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1R345W/R345W (Doyne honeycomb retinal dystrophy), and Timp3S156C/S156C (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh−/−, Ccl2−/−, Ccr2−/−, Cx3cr1−/−, and Ccl2−/−/cx3cr1−/−, oxidative stress associated genes such as Sod1−/− and Sod2 knockdown, metabolic pathway genes such as neprilysin −/− (amyloid β), transgenic mcd/mcd (cathepsin D), Cp−/−/Heph−/Y (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically

  13. Recent patents relating to diagnostic advances in age related macular degeneration (AMD).

    PubMed

    Cantsilieris, Stuart; Schache, Maria; Ashdown, M Luisa; Baird, Paul N

    2009-01-01

    Age Related Macular Degeneration (AMD) is a complex neurodegenerative disorder accounting for 50% of blind registrations in the western world. Its substantial impact on quality of life has been a main driver in research to understand its etiology, which up until recently was mostly unknown. In the last three years our understanding of the molecular pathology of AMD has increased dramatically with the identification of two major AMD loci comprising of, Complement Factor H (CFH) and a chromosome 10q26 locus consisting of the Heat Shock Serine Protease (HTRA1) and LOC387715 genes. These two loci have been described as associated with over 50% of disease in certain ethnicities. The rapid pace in our understanding of the complex biology of this disease has placed a large emphasis on gene patenting, especially with the licensing of the CFH and chromosome 10 patents to a private life science company called Optherion Inc. The patents discussed in this review highlight the important discoveries that have contributed to our understanding of AMD and provide valuable information as to where research in this area will be heading in the future.

  14. MP-1 biofeedback: luminous pattern stimulus versus acoustic biofeedback in age related macular degeneration (AMD).

    PubMed

    Vingolo, Enzo M; Salvatore, Serena; Limoli, Paolo G

    2013-03-01

    In this study we evaluated the efficacy of visual rehabilitation by means of two different types of biofeedback techniques in patients with age related macular degeneration (AMD). Thirty patients, bilaterally affected by AMD, were randomly divided in two groups: one group was treated with an acoustic biofeedback (AB group), the other was treated with luminous biofeedback of a black and white checkerboard flickering during the examination (LB group). All patients underwent a complete ophthalmological examination. Rehabilitation consisted of 12 training sessions of 10 min for each eye performed once a week for both groups. Both groups showed better visual performance after rehabilitation and luminous flickering biofeedback stimulus showed a statistically significant improvement in training the patients to modify their preferred retinal locus in comparison to acoustic biofeedback. This suggests that it might be possible in the damaged retina to override dead photoreceptor and outer retinal layers and involve residual surviving cells, as well as amplify and integrate retinal and brain cortex plasticity by using other spared channels towards associative pathways.

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

    PubMed

    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

  16. Clinical outcomes and mechanism of action for rheopheresis treatment of age-related macular degeneration (AMD).

    PubMed

    Pulido, Jose; Sanders, Donald; Winters, Jeffrey L; Klingel, Reinhard

    2005-10-01

    The primary goals are to provide a comprehensive explanation of the potential role of therapeutic apheresis in the treatment of Age-Related Macular Degeneration (AMD). Initial clinical results with this technique and a summary of current literature that addresses the mechanism of action for the Rheopheresis approach are presented. Rheopheresis has been found to be a safe and effective application of double filtration plasmapheresis (DFPP) for extracorporeal hemorheotherapy. In this report, it is proposed that Rheopheresis results in an immediate decrease in the proportion of high molecular weight proteins that could combine with the TIMP-3 fibulin complex allowing for the barely functioning retinal pigment epithelial (RPE) cells to function better and diminish the release of vascular endothelial growth factor (VEGF). Interim results from the randomized, double-masked MIRA-1 clinical trial include (1) improved vision restoration; 28.0% of Treated Primary Eyes increased by > or = 2 lines of best corrected visual acuity (BCVA) compared to 18.2% of Placebo Eyes; (2) a decline in progressive vision loss; 0.0% of treated eyes progressing to worse than 20/200 vision over the 12-month study compared to 18.2% of Placebo Eyes; (3) 57.9% of Treatment Eyes obtained improvement in their BCVA to 20/40 or better (driver's license qualification), compared to only 14.3% of Placebo Eyes 12-month post-treatment. Rheopheresis treatment shows strong promise as a viable clinical option for patients suffering from the dry form of AMD in terms of minimizing vision loss, vision restoration, and overall quality of life factors. Expanded clinical outcomes from the ongoing MIRA-1 clinical study will be valuable in the assessment of this new clinical tool for ophthalmic applications.

  17. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  18. Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images.

    PubMed

    Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

    2016-12-01

    Non-lethal macular diseases greatly impact patients' life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples.

  19. Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

    PubMed Central

    Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

    2016-01-01

    Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples. PMID:28018716

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

    PubMed

    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

    2017-08-28

    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 < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related 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.

  1. Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report.

    PubMed

    Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

    2017-09-01

    To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. In any 5-year duration, 19-28% of unilateral any AMD cases became bilateral and 27-68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. [Serum antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD)--preliminary findings].

    PubMed

    Kubicka-Trzaska, Agnieszka; Wilańska, Joanna

    2009-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. Despite the magnitude of this clinical problem, the pathogenesis of the disease remains still unclear. To determine the tissue specificity and titer of antiretinal antibodies (ARA) in sera of patients with exudative AMD. Forty-six patients (92 eyes) 16 males and 30 women with exudative AMD were stratified arbitrary into four groups of AMD activity/severity: group I (n = 19)--patients with active choroidal neovascularization (CNV) in one eye and with drusen in the other eye; group II (n = 14)--patients with bilateral CNV; group III (n = 10)--patients with CNV in one eye and with disciform scar in the contralateral eye; group IV (n = 3)--patients with bilateral disciform scars. In all patients serum ARA were determined using indirect immunofluorescence detection on normal monkey retina as antigens substrate and FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody. In all patients' serum ARA were present in the range of titres from 1:40 to 1:5120. Control sera (n = 28, 28 males) demonstrated the presence of ARA in titres 1:10 to 1:40 in 46.4% cases. High serum titres of ARA characterized AMD patients with bilateral CNV and CNV in one eye and drusen in the contralateral eye. Low titres of ARA were detected in serum of patients with bilateral disciform scars. Indirect immunofluorescence (IIF) showed eight types histological patterns of patients' sera reactivity against retinal tissue. No correlation was found between serum ARA type and macular lesion activity. Our preliminary observations indicate a common presence of various ARA in serum of patients with AMD. Thus, it cannot exclude that ARA are involved in the pathogenesis or progression of AMD.

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

    PubMed Central

    Vavvas, Demetrios G.; Daniels, Anthony B.; Kapsala, Zoi G.; Goldfarb, Jeremy W.; Ganotakis, Emmanuel; Loewenstein, John I.; Young, Lucy H.; Gragoudas, Evangelos S.; Eliott, Dean; Kim, Ivana K.; Tsilimbaris, Miltiadis K.; Miller, Joan W.

    2016-01-01

    Importance Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. Objective We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD. Design Pilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80 mg of atorvastatin daily and were monitored at baseline and every 3 months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women). Results Twenty-three subjects completed a minimum follow-up of 12 months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+ 3.3 letters, p = 0.06) in 10 patients. No subjects progressed to advanced neovascular AMD. 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. PMID:27077128

  4. Current barriers to treatment for wet age-related macular degeneration (wAMD): findings from the wAMD patient and caregiver survey.

    PubMed

    Varano, Monica; Eter, Nicole; Winyard, Steve; Wittrup-Jensen, Kim U; Navarro, Rafael; Heraghty, Julie

    2015-01-01

    A cross-sectional survey to evaluate the current management of wet age-related macular degeneration (wAMD) and to identify barriers to treatment from a patient and caregiver perspective. An ophthalmologist-devised questionnaire was given to a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections and to caregivers (paid and unpaid) to evaluate the impact of wAMD on their lives. Responders included 910 patients and 890 caregivers; wAMD was diagnosed in both eyes in 45% of patients, and 64% had been receiving injections for > 1 year. Many caregivers were a child/grandchild (47%) or partner (23%) of the patient; only 7% were professional caregivers. Most (73%) patients visited a health care professional within 1 month of experiencing vision changes and 54% began treatment immediately. Most patients and caregivers reported a number of obstacles in managing wAMD, including the treatment itself (35% and 39%, respectively). Sixteen percent of patients also missed a clinic visit. Most patients seek medical assistance promptly for a change in vision; however, about a quarter of them do not. This highlights a lack of awareness surrounding eye health and the impact of a delayed diagnosis. Most patients and caregivers identified a number of obstacles in managing wAMD.

  5. Current barriers to treatment for wet age-related macular degeneration (wAMD): findings from the wAMD patient and caregiver survey

    PubMed Central

    Varano, Monica; Eter, Nicole; Winyard, Steve; Wittrup-Jensen, Kim U; Navarro, Rafael; Heraghty, Julie

    2015-01-01

    Purpose A cross-sectional survey to evaluate the current management of wet age-related macular degeneration (wAMD) and to identify barriers to treatment from a patient and caregiver perspective. Methods An ophthalmologist-devised questionnaire was given to a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections and to caregivers (paid and unpaid) to evaluate the impact of wAMD on their lives. Results Responders included 910 patients and 890 caregivers; wAMD was diagnosed in both eyes in 45% of patients, and 64% had been receiving injections for > 1 year. Many caregivers were a child/grandchild (47%) or partner (23%) of the patient; only 7% were professional caregivers. Most (73%) patients visited a health care professional within 1 month of experiencing vision changes and 54% began treatment immediately. Most patients and caregivers reported a number of obstacles in managing wAMD, including the treatment itself (35% and 39%, respectively). Sixteen percent of patients also missed a clinic visit. Conclusion Most patients seek medical assistance promptly for a change in vision; however, about a quarter of them do not. This highlights a lack of awareness surrounding eye health and the impact of a delayed diagnosis. Most patients and caregivers identified a number of obstacles in managing wAMD. PMID:26664038

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

    PubMed

    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.

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

    PubMed Central

    Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

    2016-01-01

    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. PMID:27941641

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

    PubMed

    Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

    2016-12-08

    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. miRNAs, single nucleotide polymorphisms (SNPs) and age-related macular degeneration (AMD).

    PubMed

    SanGiovanni, John Paul; SanGiovanni, Peter M; Sapieha, Przemysław; De Guire, Vincent

    2017-05-01

    Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD. The presence of certain single nucleotide polymorphisms (SNPs) may influence the explanatory value of these biomarkers. Here we present findings from an integrated approach used to determine whether AAMD-associated SNPs have the capacity to influence miRNA-mRNA pairing and, if so, to what extent such pairing may be manifested in a discrete AAMD transcriptome. Using a panel of 8854 SNPs associated with AAMD at p-values ≤5.0E-7 from a cohort of >30,000 elderly people, we identified SNPs in miRNA target-encoding constituents of: (1) regulator of complement activation (RCA) genes (rs390679, CFHR1, p≤2.14E-214 | rs12140421, CFHR3, p≤4.63E-29); (2) genes of major histocompatibility complex (MHC) loci (rs4151672, CFB, p≤8.91E-41 | rs115404146, HLA-C, p≤6.32E-12 | rs1055821, HLA-B, p≤1.93E-9 | rs1063355, HLA-DQB1, p≤6.82E-14); and (3) genes of the 10q26 AAMD locus (rs1045216, PLEKHA1, p≤4.17E-142 | rs2672603, ARMS2, p≤7.14E-46). We used these findings with existing data on AAMD-related retinal miRNA and transcript profiles for the purpose of making inferences on SNP-mRNA-miRNA-AAMD relationships. Four of 12 miRNAs significantly elevated in AAMD retina (hsa-miR-155-5p, hsa-let-7a-5p, hsa-let-7b-5p hsa-let-7d-5p) also showed strong pairing capacity (TarBase 7.1 context++ score <-0.2, miRanda 3.3 pairing score >150) with miRNA target transcripts encoded by AAMD-associated SNPs resident in HLA-DQB1 (rs1063355, hsa-miR-155-5p) and TGFBR1 (rs868, hsa-let-7). Three of the 12 miRNAs overexpressed in AAMD retina are inducible by NFkB and have high affinity targets in the complement factor H (CFH) mRNA 3' UTR. We used ENSEMBL to identify polymorphic regions in the CFH mRNA 3' UTR with the capacity to disrupt miRNA-mRNA pairing. Two variants (rs766666504 and rs459598) existed in DNA

  10. AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Gheorghe, Andreea; Mahdi, Labib; Musat, Ovidiu

    2015-01-01

    The objective of our study was to review the current knowledge on Age- Related Macular Degeneration, including pathogenesis, ocular manifestations, diagnosis and ancillary testing. Relevant publications on Age-Related Macular Degeneration that were published until 2014. Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterized by the appearance of drusen in the macula, accompanied by choroidal neovascularization (CNV) or geographic atrophy.

  11. Heat shock proteins as gatekeepers of proteolytic pathways-Implications for age-related macular degeneration (AMD).

    PubMed

    Kaarniranta, Kai; Salminen, Antero; Eskelinen, Eeva-Liisa; Kopitz, Jürgen

    2009-04-01

    Age-related macular degeneration (AMD) is the major diagnosis for severe and irreversible central loss of vision in elderly people in the developed countries. The loss of vision involves primarily a progressive degeneration and cell death of postmitotic retinal pigment epithelial cells (RPE), which secondarily evokes adverse effects on photoreceptor cells. The RPE cells are exposed to chronic oxidative stress from three sources: their high levels of oxygen consumption, their exposure to the high levels of lipid peroxidation derived from the photoreceptor outer segments and their exposure to constant light stimuli. Cells increase the expression of heat shock proteins (HSPs) in order to normalize their growth conditions in response to various environmental stress factors, e.g. oxidative stress. The HSPs function as molecular chaperones by preventing the accumulation of cellular cytotoxic protein aggregates and assisting in correct folding of both nascent and misfolded proteins. Increased HSPs levels are observed in the retina of AMD patients, evidence of stressed tissue. A hallmark of RPE cell aging is lysosomal lipofuscin accumulation reflecting a weakened capacity to degrade proteins in lysosomes. The presence of lipofuscin increases the misfolding of intracellular proteins, which evokes additional stress in the RPE cells. If the capacity of HSPs to repair protein damages is overwhelmed, then the proteins are mainly cleared in proteasomes or in lysosomes. In this review, we discuss the role of heat shock proteins, proteasomes, and lysosomes and autophagic processes in RPE cell proteolysis and how these might be involved in development of AMD. In addition to classical lysosomal proteolysis, we focus on the increasing evidence that, HSPs, proteasomes and autophagy regulate protein turnover in the RPE cells and thus have important roles in AMD disease.

  12. Age-Related Macular Degeneration

    MedlinePlus

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  13. [Guidelines of clinical practice of the SERV: treatment of exudative age-related macular degeneration (AMD)].

    PubMed

    Ruiz-Moreno, J M; Arias-Barquet, L; Armadá-Maresca, F; Boixadera-Espax, A; García-Layana, A; Gómez-Ulla-de-Irazazábal, F; Monés-Carilla, J; Piñero-Bustamante, A; Suárez-de-Figueroa, M

    2009-07-01

    Age related macular degeneration (ARMD) in its neovascular form is a serious disease which produces legal blindness in many patients with poor prognosis if left untreated. We intend to establish a clinical guide with the different therapeutic options that exist nowadays, which may help the ophthalmologists in their clinical practice. A group of medical retina experts selected by SERV have evaluated the results of different published studies with the drugs currently available, obtaining an evidence-based consensus. Some recommendations have been established for diagnosis, treatment and monitoring of patients with neovascular ARMD. The intravitreal injection of ranibizumab at a dosage of 0.5 mg produces significant improvement of visual acuity in subfoveal lesions, according to data obtained from studies with the highest level of evidence. It should be considered as a first choice drug. The use of bevacizumab, a drug with not approved indication for intraocular use, nor for the treatment of neovascular ARMD can reach a result which is closer to the ones obtained with ranibizumab than to those obtained with photodynamic therapy (PDT) and pegaptanib. The use of intravitreal pegaptanib sodium in intravitreal injection at a dosage of 0.3 mg as a treatment for subfoveal lesions can obtain similar results to the TFD, but with a wider range of injuries. The results of the evidence-based studies are a good guide for the treatment of this disease.

  14. Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT).

    PubMed

    Hagstrom, Stephanie A; Ying, Gui-Shuang; Pauer, Gayle J T; Sturgill-Short, Gwen M; Huang, Jiayan; Callanan, David G; Kim, Ivana K; Klein, Michael L; Maguire, Maureen G; Martin, Daniel F

    2013-03-01

    To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD. Clinical trial. Eight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P≤0.01 was considered statistically significant. No statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab

  15. Benedictine monastery on the Island of Rab hides the mystery of sunlight influence on development of macular degeneration (AMD). Is a harmful sunlight, risk factor or cause of macular degeneration?

    PubMed

    Vojniković, Bozo; Vojniković, Davor

    2010-04-01

    Benedictine Monastery of St. Andrew is probably the oldest existing Benedictine monastery in this area. According to hundreds of years of legend, it was founded in 1018 year. In clinical examination about the possibility of the macular degeneration occurrence in 15 Benedictine sisters, we found the age-related macular degeneration (AMD) in two cases only. In 13 other sisters aging 27, 60, 67years, the fundus picture was like in a baby, vision, visual field and meridian thresholds were normal. What is the explanation for this phenomenon? Two sisters with AMD work and live as the farm workers, but the other sisters live in closed monastery with very low natural sunlight, approximately 300-500 lx. In conclusion, the earlier author's experimental and clinical works follow the consequence that without exposure of eyes to harmful higher doses of sunlight, it is not possible to develop AMD. The harmful cumulative dose of sunlight is not the risk factor but the cause, including the inheritance, for AMD development.

  16. [Laser photocoagulation and photodynamic therapy (PDT) with verteporfin for retinal angiomatous proliferation (RAP) in age-related macular degeneration (AMD)].

    PubMed

    Stoffelns, B M; Kramann, C; Schoepfer, K

    2008-05-01

    Retinal angiomatous proliferation (RAP) is a subtype of neovascular age-related macular degeneration (AMD) with particularly bad prognosis. Diverse treatment modalities are performed. This is a retrospective review on the treatment results of 41 consecutive patients from 1/2003 to 12/2005 with RAP stage 1-3 (Yannuzzi classification), who were treated with laser photocoagulation, photodynamic therapy (PDT) and intravitreal injection of triamcinolone acetonide (IVT). Follow-up was 12 months minimally. In RAP stage I complete closure of the vascular lesion in 14 / 22 eyes was achieved by 1.2 +/- 0.5 sessions of laser photocoagulation (4 x combined with IVT) and in 3/14 eyes with photodynamic therapy (2 +/- 0.5 sessions). In RAP stage II closure of the lesion was achieved by 3.2 +/- 0.6 sessions of photodynamic therapy in 6/14 eyes (4 x combined with IVT). In RAP stage III closure of the lesion was achieved by 3.2 +/- 0.4 sessions of photodynamic therapy in 0 / 5 eyes (3 x combined with IVT). A rip of the retinal pigment epithelium was observed in 2/14 eyes of RAP stage II and 2/5 eyes of RAP stage III. Visual acuity improved in 9/17 eyes with occlusion of RAP stage I. Without closure of the vascular lesion all eyes got legally blind (visual acuity 1/50 or less). Early detection and subsequent direct treatment of RAP stage I in AMD is recommended. In advanced stages anatomical closure of the vascular complex is rarely achieved and the risk is improved for development of tears in the retinal pigment epithelium and getting legally blind.

  17. Optical coherence tomography angiography reproducibility of lesion size measurements in neovascular age-related macular degeneration (AMD).

    PubMed

    Amoroso, Francesca; Miere, Alexandra; Semoun, Oudy; Jung, Camille; Capuano, Vittorio; Souied, Eric H

    2017-08-30

    To evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA). Prospective non-interventional study. Consecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two sequential OCTA examinations (AngioVue, Optovue, Fremont, California, USA), performed by the same trained examiner. Neovascular lesion area was then measured on both examinations in the choriocapillaris automatic segmentation by two masked readers, using the semiautomated measuring software embedded in the instrument. Two measuring features were used: the first corresponding to the total manually contoured lesion area with the flow draw tool (select area) and the second to the total area of solely vessels with high flow within the lesion (vessel area). These measurements were then compared in order to assess both the reproducibility of OCTA examination and the interuser agreement with the embedded software. Forty-eight eyes of 46 patients (77.4 mean age,+/-8.2 SD, range from 62 to 95 years old, eight men, 38 women) were included in our study. Mean choroidal neovascularisation area was of 0.72+/-0.7 mm(2) for the first measurement and 0.75+/-0.76 mm(2) for the second measurement; difference between the first and the second measurement was 0.03 mm(2). Intrauser agreement was of 0.98 (CI 0.98 to 0.99) for both 'vessel area' and 'select area' features. Interuser agreement was of 0.98 (CI 0.97 to 0.99) for 'select area' and 'vessel area' features. Our data suggest that OCTA provide reproducible imaging for evaluation of the neovascular size in the setting of AMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Neovascular age-related macular degeneration management in the third year: final results from the TREX-AMD randomised trial.

    PubMed

    Wykoff, Charles C; Ou, William C; Croft, Daniel E; Payne, John F; Brown, David M; Clark, W Lloyd; Abdelfattah, Nizar Saleh; Sadda, SriniVas R

    2017-08-04

    Prospectively evaluate outcomes in the third year of neovascular age-related macular degeneration (AMD) management using ranibizumab with continued treat and extend (TREX) dosing compared with monthly visits with retreatment upon evidence of exudative disease activity (PRN, pro re nata). Subjects with treatment-naïve neovascular AMD were randomised 1:2 to Monthly or TREX and managed through 2 years. In the third year, subjects randomised to Monthly were managed PRN while subjects randomised to TREX were continued on TREX dosing or transitioned to PRN after achieving an interval of 12 weeks between visits. Sixty subjects enrolled and 46 (77%) completed month 36 (M36). Transition from Monthly to PRN was associated with a decline in best corrected visual acuity (BCVA) (+10.5 letters (month 24) to +5.4 (M36, p=0.09)); three (15%) subjects required no dosing during year 3, and 47% (114/243) of possible PRN injections were delivered, yielding a mean of 6.1 injections during year 3. Among the 9 (23%) TREX subjects transitioned to PRN, the need for ongoing anti-vascular endothelial growth factor retreatments was small, with 4 (4%) intravitreal injections being delivered among 106 PRN visits; this subgroup displayed an inferior BCVA trajectory compared with the remainder of subjects. Outcomes among subjects continued on TREX were more favourable, with a mean gain of +5.0 letters at M36. Upon transition to PRN, subjects randomised to monthly dosing experienced a decline in BCVA. Among subjects initially randomised to TREX who transitioned to PRN after achieving a 12-week interval between visits, the overall need for additional treatment was low. NCT01748292, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Age-Related Macular Degeneration.

    PubMed

    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.

  20. Dry Macular Degeneration

    MedlinePlus

    ... delay vision loss due to dry macular degeneration. Symptoms Dry macular degeneration symptoms usually develop gradually and without pain. They may ... of printed words Decreased intensity or brightness of ... causes total blindness. Dry macular degeneration is one of two types ...

  1. Macular degeneration (image)

    MedlinePlus

    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 ...

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

    PubMed

    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

  3. A brief discussion on lipid activated nuclear receptors and their potential role in regulating microglia in age-related macular degeneration (AMD)

    PubMed Central

    Choudhary, Mayur; Malek, Goldis

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness and visual impairment in individuals over 60 years of age in the Western World. A common morphological denominator in all forms of AMD is the accumulation of microglia within the sub-retinal space, which is believed to be a contributing factor to AMD progression. However, the signaling pathway and molecular players regulating microglial recruitment have not been completely identified. Multiple in-vitro and in-vivo studies, to date, have highlighted the contributions of nuclear receptor ligands in the treatment of inflammation related disorders such as atherosclerosis and Alzheimer’s disease. Given that inflammation and the immune response play a vital role in the initiation and progression of AMD, in this brief review we will highlight some of these studies with a particular focus on the lipid activated “adopted orphan” nuclear receptors, the liver x receptors (LXRs) and the peroxisome proliferator-activated receptors (PPARs). The results of these studies strongly support the rationale that treatment with LXR and PPAR ligands may ameliorate microglial activation in the sub-retinal space and ultimately slow down or reverse the progression of AMD. PMID:26427392

  4. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical 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 injection PMID:21654887

  5. Macular Degeneration

    MedlinePlus

    ... die. There are two types: wet and dry. Wet AMD happens when abnormal blood vessels grow under the ... new blood vessels often leak blood and fluid. Wet AMD damages the macula quickly. Blurred vision is a ...

  6. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    ClinicalTrials.gov

    2016-10-20

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  7. The major risk alleles of age-related macular degeneration (AMD) in CFH do not play a major role in rheumatoid arthritis (RA).

    PubMed

    Trouw, L A; Böhringer, S; Daha, N A; Stahl, E A; Raychaudhuri, S; Kurreeman, F A; Stoeken-Rijsbergen, G; Houwing-Duistermaat, J J; Huizinga, T W; Toes, R E

    2011-12-01

    Because activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. For this purpose we genotyped single nucleotide polymorphisms (SNPs) in a Dutch set of RA patients and controls. Similarly, a meta-analysis using a Spanish cohort of RA as well as six large genome-wide association studies (GWAS) studies was performed. For these SNPs we analysed more than 6000 patients and 20,000 controls. The CFH variants, I62V, Y402H, IVS1 and IVS10, known to associate strongly with AMD, did not show a significant association with the risk of developing RA despite a strong statistical power to detect such differences. In conclusion, the major risk alleles of AMD in CFH do not have a similar effect on developing RA.

  8. [Influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration (AMD)].

    PubMed

    Włodarek, Dariusz; Głabska, Dominika

    2011-01-01

    The aim of the study was analysis of the influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration The object of conducted analysis were 127 nutrition questionnaires from 64 individuals with AMD (44 female, 20 male) and 63 without AMD--control group (49 female, 14 male). The age of participants was 50-88. The nutrition questionnaire concerned: AMD and its course, consumption of lutein-rich products and lutein supplementation. Lutein supply was assessed on the base of most often consumed products and lutein content in typical servings as well as on the base of applied supplementation. Patients with AMD, in comparison with control group, were significantly more often choosing green bean, parsley, dill (Anethum graveolens) and young beetroot leaves, as well as were consuming more diversified lutein-rich products. Lutein supply from diet was significanly increased in case of spinach consumption (very high in lutein) and broccoli consumption (high in lutein and chosen relatively often). Other products did not cause increase of lutein supply from diet, even if they evoked increase of lutein content in the typical serving or of quantity of servings. Patients with AMD, in comparison with healthy individuals, more often consume lutein-rich products, but lutein supply from diet in both groups do not differ. Significant increase of lutein supply may be achieved only by consumption of products characterized by the highest content of it. Patients with AMD, in comparison with healthy individuals, more often apply lutein supplementation, that influences lutein daily supply.

  9. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  10. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  11. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.

    PubMed

    Schubert, Timm; Gleiser, Corinna; Heiduschka, Peter; Franz, Christoph; Nagel-Wolfrum, Kerstin; Sahaboglu, Ayse; Weisschuh, Nicole; Eske, Gordon; Rohbock, Karin; Rieger, Norman; Paquet-Durand, François; Wissinger, Bernd; Wolfrum, Uwe; Hirt, Bernhard; Singer, Wibke; Rüttiger, Lukas; Zimmermann, Ulrike; Knipper, Marlies

    2015-10-01

    The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms.

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

    PubMed

    Varano, Monica; Eter, Nicole; Winyard, Steve; Wittrup-Jensen, Kim U; Navarro, Rafael; Heraghty, Julie

    2016-01-01

    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). The survey was performed in nine countries using an ophthalmologist-devised questionnaire. 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. wAMD has a significant negative impact on the lives of patients, including vision-related depression, poor mobility, and limitations in day-to-day activities. The impact on nonprofessional caregivers may be underestimated in terms of emotional impact (such as depression) and loss of productivity.

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

    PubMed Central

    Varano, Monica; Eter, Nicole; Winyard, Steve; Wittrup-Jensen, Kim U; Navarro, Rafael; Heraghty, Julie

    2016-01-01

    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. Conclusion wAMD has a significant negative impact on the lives of patients, including vision-related depression, poor mobility, and limitations in day-to-day activities. The impact on nonprofessional caregivers may be underestimated in terms of emotional impact (such as depression) and loss of productivity. PMID:26893539

  16. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  17. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  18. A Candidate Gene Association Study Identifies DAPL1 as a Female-Specific Susceptibility Locus for Age-Related Macular Degeneration (AMD).

    PubMed

    Grassmann, Felix; Friedrich, Ulrike; Fauser, Sascha; Schick, Tina; Milenkovic, Andrea; Schulz, Heidi L; von Strachwitz, Claudia N; Bettecken, Thomas; Lichtner, Peter; Meitinger, Thomas; Arend, Nicole; Wolf, Armin; Haritoglou, Christos; Rudolph, Guenther; Chakravarthy, Usha; Silvestri, Giuliana; McKay, Gareth J; Freitag-Wolf, Sandra; Krawczak, Michael; Smith, R Theodore; Merriam, John C; Merriam, Joanna E; Allikmets, Rando; Heid, Iris M; Weber, Bernhard H F

    2015-06-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among white caucasians over the age of 50 years with a prevalence rate expected to increase markedly with an anticipated increase in the life span of the world population. To further expand our knowledge of the genetic architecture of the disease, we pursued a candidate gene approach assessing 25 genes and a total of 109 variants. Of these, synonymous single nucleotide polymorphism (SNP) rs17810398 located in death-associated protein-like 1 (DAPL1) was found to be associated with AMD in a joint analysis of 3,229 cases and 2,835 controls from five studies [combined PADJ = 1.15 × 10(-6), OR 1.332 (1.187-1.496)]. This association was characterized by a highly significant sex difference (Pdiff = 0.0032) in that it was clearly confined to females with genome-wide significance [PADJ = 2.62 × 10(-8), OR 1.541 (1.324-1.796); males: PADJ = 0.382, OR 1.084 (0.905-1.298)]. By targeted resequencing of risk and non-risk associated haplotypes in the DAPL1 locus, we identified additional potentially functional risk variants, namely a common 897-bp deletion and a SNP predicted to affect a putative binding site of an exonic splicing enhancer. We show that the risk haplotype correlates with a reduced retinal transcript level of two, less frequent, non-canonical DAPL1 isoforms. DAPL1 plays a role in epithelial differentiation and may be involved in apoptotic processes thereby suggesting a possible novel pathway in AMD pathogenesis.

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

    SciTech Connect

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

    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.

  20. UK Age-Related Macular Degeneration Electronic Medical Record System (AMD EMR) Users Group Report IV: Incidence of Blindness and Sight Impairment in Ranibizumab-Treated Patients.

    PubMed

    Johnston, Robert L; Lee, Aaron Y; Buckle, Miranda; Antcliff, Richard; Bailey, Clare; McKibbin, Martin; Chakravarthy, Usha; Tufail, Adnan

    2016-11-01

    To study the incidence of blindness and sight impairment in treatment-naive patients receiving ranibizumab (Lucentis) for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) National Health Service. Multicenter nAMD database study. A total of 11 135 patients who collectively received 92 976 treatment episodes to 12 951 eyes. Data were extracted from 14 UK centers using the same electronic medical record system (EMR). The EMR-mandated collection of a data set (defined before first data entry) including: age, Early Treatment Diabetic Retinopathy Study visual acuity letter score (VA) for both eyes at all visits, and injection episodes. Participating centers used overwhelmingly a pro re nata re-treatment posology at intended monthly follow-up visits following a loading phase of 3 monthly injections. Incidence of blindness and sight impairment (VA in the better-seeing eye <38 letters [≤20/200 Snellen, approximately], and <68 letters [≤20/50 Snellen, approximately] at 2 consecutive visits, or 1 visit if no further follow-up data) in each year after initiating treatment. Information from >300 000 clinic visits (2.8 million data points) collected over 5 years was collated from 14 centers. Mean age at first treatment was 79.7 years (standard deviation = 9.19 years), with a female preponderance (63%). The mean (median) VA at baseline in the better-seeing eye was 67.2 (72.0) letters, 20/40- (20/40+) approximate Snellen conversion. The cumulative incidence of new blindness and sight impairment in patients with treated nAMD in at least 1 eye at years 1 to 4 after first injection were 5.1%, 8.6%, 12% and 15.6% for new blindness and 29.6%, 41.0%, 48.7%, and 53.7% for new sight impairment, but with significant reductions in the rates between year cohorts initiating treatment (blindness [P = 4.72 × 10(-08)], sight impaired [P = 3.27 × 10(-06)]). To the best of our knowledge, this is the first multicenter real-world study on the

  1. Combination of Aflibercept and Bromfenac Therapy in Age-Related Macular Degeneration: A Pilot Study Aflibercept and Bromfenac in AMD.

    PubMed

    Wyględowska-Promieńska, Dorota; Piotrowska-Gwóźdź, Anna; Piotrowska-Seweryn, Agnieszka; Mazur-Piotrowska, Grażyna

    2015-12-15

    BACKGROUND Among many protocols for treatment of exudative AMD, combined therapy of anti-VEGF agents and non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an ideal alternative to monotherapy based on ranibizumab or bevacizumab. The aim of this study was to evaluate the effectiveness of aflibercept and bromfenac in the treatment of exudative AMD. MATERIAL AND METHODS The study was conducted on a group of 27 patients with exudative AMD who were administered intravitreal aflibercept and topical bromfenac (study group) once a month. Additional injections were administered up to 3 months after the third administration, depending on response to treatment. The control group consisted of subjects treated with aflibercept only. Visual acuity and anatomical outcomes in optical coherence tomography (OCT) were assessed at baseline visit, 4 months after the first dose, and 6 months after the start of the treatment. RESULTS Visual acuity improved over time in the study group and the differences between the groups were statistically significant. No statistically significant differences were found in OCT parameters. CONCLUSIONS Combined therapy of aflibercept and bromfenac in the treatment of wet AMD is more effective than single aflibercept therapy.

  2. MicroRNA Expression Analysis in Serum of Patients with Congenital Hemochromatosis and Age-Related Macular Degeneration (AMD).

    PubMed

    Szemraj, Maciej; Oszajca, Katarzyna; Szemraj, Janusz; Jurowski, Piotr

    2017-08-22

    BACKGROUND Congenital hemochromatosis is a disorder caused by mutations of genes involved in iron metabolism, leading to increased levels of iron concentration in tissues and serum. High concentrations of iron can lead to the development of AMD. The aim of this study was to analyze circulating miRNAs in the serum of congenital hemochromatosis patients with AMD and their correlation with the expression of genes involved in iron metabolism. MATERIAL AND METHODS Peripheral blood monolayer cells and serum were obtained from patients with congenital hemochromatosis, congenital hemochromatosis and AMD, AMD patients without congenital hemochromatosis, and healthy controls. Serum miRNAs expressions were analyzed by RT-PCR (qRT-PCR) using TaqMan MicroRNA probes, and proteins levels were measured by ELSA kits. Gene polymorphisms in TF and TFRC genes were determined using the TaqMan discrimination assay. RESULTS Statistical analysis of the miRNAs expressions selected for further study the miR-31, miR-133a, miR-141, miR-145, miR-149, and miR-182, which are involved in the posttranscriptional expression of iron-related genes: TF, TFRI, DMT1, FTL, and FPN1. It was discovered that the observed changes in the expressions of the miRNAs was correlated with the level of protein in the serum of the analyzed genes. There were no statistically significant differences in the distribution of genotype and allele frequencies in TF and TFRC genes between analyzed groups of patients. CONCLUSIONS The differences studied in the miRNA serum profile, in conjunction with the changes in the analyzed protein levels, may be useful in the early detection of congenital hemochromatosis in patients who may develop AMD disease.

  3. Wet Macular Degeneration

    MedlinePlus

    ... has a hereditary component. Researchers have identified several genes related to developing the condition. Smoking. Smoking cigarettes or being regularly exposed to smoke significantly increases your risk of macular degeneration. Obesity. Research indicates that being obese increases the chance ...

  4. [Age related macular degeneration].

    PubMed

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  5. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  8. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    MedlinePlus

    ... point to same risk gene for age-related macular degeneration NIH-funded research helps unravel the biology of ... rare, but powerful risk factor for age-related macular degeneration (AMD), a common cause of vision loss in ...

  9. A Retrospective Study of Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration (nAMD) in Australia and the United Kingdom.

    PubMed

    Johnston, Robert L; Carius, Hans-Joachim; Skelly, Adrian; Ferreira, Alberto; Milnes, Fran; Mitchell, Paul

    2017-03-01

    Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss among persons aged 65 years and older. Anti-vascular endothelial growth factor (anti-VEGF) treatment is the recommended standard of care. The current study compares the effectiveness of ranibizumab in routine clinical practice in two countries that generally apply two different treatment regimens, treat-and-extend (T&E) in Australia or pro re nata (PRN) in the UK. This retrospective, comparative, non-randomised cohort study is based on patients' data from electronic medical record (EMR) databases in Australia and the UK. Treatment regimens were defined based on location, with Australia as a proxy for analysing T&E and UK as a proxy for analysing PRN. The study included patients with a diagnosis of nAMD who started treatment with ranibizumab between January 2009 and July 2014. A total of 647 eyes of 570 patients in Australia and 3187 eyes of 2755 patients in the UK with complete 12-months follow-up were analysed. Baseline patient characteristics were comparable between the two cohorts. After 1 year of treatment, T&E-treated eyes achieved higher mean (±SE) visual acuity (VA) gains (5.00 ± 0.54 letters [95% confidence interval (CI) 3.93-6.06]) than PRN-treated eyes [3.04 ± 0.24 letters (95% CI 2.57-3.51); difference in means 2.07 ± 0.69 (95% CI 0.73-3.41), p < 0.001]. Non-inferiority of T&E compared to PRN was concluded based on the change in mean visual acuity gains at 12 months. Over the 12-month follow-up, T&E-treated eyes received a higher mean [±standard deviation (SD)] number of injections (9.29 ± 2.43) than PRN-treated eyes (6.04 ± 2.19) (p < 0.0001). Australian patients had a lower mean (±SD) number of total clinic visits (10.29 ± 2.90) than UK patients (11.47 ± 2.93) (p < 0.0001). The higher injection frequency in the T&E cohort may account for the trend toward improved vision. Novartis Pharma AG, Basel, Switzerland.

  10. Cataracts and macular degeneration.

    PubMed

    Shoch, D

    1979-09-01

    The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.

  11. Depression in Age-Related Macular Degeneration.

    PubMed

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depression, and summarizes interventions for preventing depression in this high-risk group.

  12. Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

    PubMed Central

    Kang, Eui Chun; Koh, Hyoung Jun

    2015-01-01

    Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA. PMID:26425354

  13. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  14. Smoking and age-related macular degeneration: review and update.

    PubMed

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Dolz-Marco, Rosa; Pons-Vázquez, Sheila; Pinazo-Durán, M Dolores; Gómez-Ulla, Francisco; Arévalo, J Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  15. Complement pathway biomarkers and age-related macular degeneration

    PubMed Central

    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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  17. Nutritional modulation of age-related macular degeneration

    USDA-ARS?s Scientific Manuscript database

    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...

  18. Prevention of age-related macular degeneration

    PubMed Central

    Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2010-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

  19. Genetics Home Reference: Stargardt macular degeneration

    MedlinePlus

    ... Genetics Home Health Conditions Stargardt macular degeneration Stargardt macular degeneration Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Stargardt macular degeneration is a genetic eye disorder that causes progressive ...

  20. Method development to quantify Bv8 expression in circulating CD11b+ cells in patients with neovascular age-related macular degeneration (nvAMD) exhibiting Anti-VEGF refractoriness.

    PubMed

    Catchpole, Timothy; Daniels, Tad; Perkins, Jill; Csaky, Karl G

    2016-07-01

    A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. Prokineticin-2 (Bv8) expression in CD11b(+) cells has been linked to anti-VEGF response. We have developed a reproducible method to quantify gene expression in circulating CD11b + cells. Utilizing this method we tested the hypothesis that high Bv8 expression in circulating CD11b(+) cells is associated with anti-VEGF refractoriness in nvAMD patients. Two groups of nvAMD subjects undergoing treatment with anti-VEGF agents were recruited and classified as refractory or non-refractory to anti-VEGF treatment (n = 33 for each group). Two blood draws were obtained from each subject 1-9 months apart. Peripheral blood mononuclear cells (PBMCs) were isolated and CD11b(+) cells were purified via magnetic bead separation. RNA was purified, and relative expression of Bv8 among the subjects was compared via quantitative PCR analysis. Utilizing this approach no significant difference was detected in the mean LogRQ values between the first and second blood draws (t-test, p = 0.826) indicating low intra-patient variability and demonstrating good reproducibility of the assay. There was no significant difference in Bv8 expression between nvAMD subjects classified as refractory versus non-refractory. We were unable to find a correlation between Bv8 expression in CD11b + cells and anti-VEGF refractoriness in human nvAMD subjects. Relatively high expression in Bv8 in these subjects did not correlate with clinical treatment history, as measured by the frequency of injections. Utilizing this well characterized technique, studies are underway to examine alternative gene expression profiles in various circulating cell populations that may contribute to anti-VEGF refractoriness.

  1. Vitreomacular traction and age-related macular degeneration.

    PubMed

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  2. Age-related macular degeneration and the aging eye

    PubMed Central

    Ehrlich, Rita; Harris, Alon; Kheradiya, Nisha S; Winston, Diana M; Ciulla, Thomas A; Wirostko, Barbara

    2008-01-01

    Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch’s membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly. PMID:18982917

  3. Macular degeneration in an arc welder.

    PubMed

    Kim, Eun A; Kim, Byung-Gyu; Yi, Cheol-Ho; Kim, Il Gon; Chae, Chang-Ho; Kang, Seong-Kyu

    2007-04-01

    A male welder who had been working in an industrial machine plant for more than 20 years experienced acute intense pain in his left eye with continuous lacrimation while performing arc welding in 1997. Later in 1997, at the age of 39 yr, macular edema was found in his left eye. He was diagnosed with macular degeneration (MD) of the left eye in 2002, and with right eye MD in 2004. Radiation in the visible and near infrared (IR) spectra penetrates the eye and is absorbed by the retina, possibly causing thermal or photochemical damage. Such retinal damage may be permanent and, therefore, sight-threatening. The young age and history of an acute painful eye injury are not consistent with age related macular degeneration (AMD) but rather is likely maculopathy caused by welding arc exposure.

  4. Animal models of age related macular degeneration.

    PubMed

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

    2012-08-01

    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.

  5. Animal models of age related macular degeneration

    PubMed Central

    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

  6. The genetics of age-related macular degeneration.

    PubMed

    Guymer, Robyn

    2001-07-01

    AIM: To review the genetics of age-related macular degeneration (AMD). The pathogenesis of AMD, the leading cause of severe visual disability and blindness in our community, remains unknown. However, AMD is regarded as a genetic disease where family history of AMD is a significant risk factor for the disease. Understanding the genetic factors associated with AMD offers the greatest chance for understanding the underlying disease processes. METHODS: Through a review of the literature and the use of original research findings, the current knowledge of the genetics of AMD is explored. CONCLUSION: AMD is increasing in prevalence and remains a major challenge for eye heath providers. Finding the genes that are associated with AMD offers the greatest chance for the development of preventative strategies and treatments.

  7. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  8. Cognitive dysfunction and age-related macular degeneration.

    PubMed

    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.

  9. Juvenile-Onset Macular Degeneration and Allied Disorders

    PubMed Central

    North, Victoria; Gelman, Rony; Tsang, Stephen H.

    2015-01-01

    While age-related macular degeneration (AMD) is a leading cause of central vision loss among the elderly, many inherited diseases that present earlier in life share features of AMD. These diseases of juvenile-onset macular degeneration include Stargardt disease, Best disease, retinitis pigmentosa, X-linked retinoschisis, and other allied disorders. In particular, they can be accompanied by the appearance of drusen, geographic atrophy, macular hyperpigmentation, choroidal neovascularization, and disciform scarring just as in AMD, and often may be confused for the adult form of the disease. Diagnosis based on funduscopic findings alone can be challenging. However, the use of diagnostic studies such as electroretinography, electrooculography, optical coherence tomography, and fundus autofluorescence in conjunction with genetic testing can lead to an accurate diagnosis. PMID:24732760

  10. Nutritional supplements for age-related macular degeneration

    PubMed Central

    Krishnadev, Nupura; Meleth, Annal D.; Chew, Emily Y.

    2010-01-01

    Purpose of review Age-related macular degeneration, a leading cause of visual loss in older adults, has limited therapeutic options. This review describes the current literature on the role of nutritional supplementation in primary and secondary prevention of AMD. Recent findings Many observational studies have explored the association between diet, nutrient intake, and AMD. In particular, high dietary intakes of omega 3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalent and incident AMD. However, the Age-Related Eye Disease Study (AREDS) is the only large-scale randomized controlled clinical trial to show a 25% beneficial effect of nutritional supplementation in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye at 5 years of follow-up. Based on the results of AREDS, these patients are recommended to take AREDS formulation of vitamins C, E, beta-carotene, and zinc with copper. Summary At the present time, there is insufficient evidence in the literature to recommend routine nutritional supplementation in healthy adults for primary prevention of AMD. However, patients with intermediate risk of AMD or advanced AMD in one eye should consider taking AREDS-type supplements. Observational studies have also suggested benefit from increased dietary intake of macular xanthophylls and omega-3 fatty acids. These are currently being evaluated prospectively in a randomized controlled clinical trial, the Age-Related Eye Disease Study 2 (AREDS2). PMID:20216418

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Fosse, Per; Valberg, Arne

    2004-01-01

    This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

  13. Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

    2005-01-01

    Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

  14. Early detection of age related macular degeneration: current status.

    PubMed

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  15. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  16. Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex.

    PubMed

    Bhutto, Imran; Lutty, Gerard

    2012-08-01

    There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch's membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85-90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10-15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex.

  17. Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex

    PubMed Central

    Bhutto, Imran; Lutty, Gerard

    2012-01-01

    There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch’s membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85–90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10–15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex. PMID:22542780

  18. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  19. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    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.

  20. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  1. Age-related macular degeneration

    PubMed Central

    Coleman, Hanna R; Chan, Chi-Chao; Ferris, Frederick L; Chew, Emily Y

    2008-01-01

    Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration. PMID:19027484

  2. Highly Penetrant Alleles in Age-Related Macular Degeneration

    PubMed Central

    den Hollander, Anneke I.; de Jong, Eiko K.

    2015-01-01

    Age-related macular degeneration (AMD) is a complex disease caused by a combination of genetic and environmental factors. Genome-wide association studies have identified several common genetic variants associated with AMD, which together account for 15%–65% of the heritability of AMD. Multiple hypotheses to clarify the unexplained portion of genetic variance have been proposed, such as gene–gene interactions, gene–environment interactions, structural variations, epigenetics, and rare variants. Several studies support a role for rare variants with large effect sizes in the pathogenesis of AMD. In this work, we review the methods that can be used to detect rare variants in common diseases, as well as the recent progress that has been made in the identification of rare variants in AMD. In addition, the relevance of these rare variants for diagnosis, prognosis, and treatment of AMD is highlighted. PMID:25377141

  3. A Revised Hemodynamic Theory of Age-Related Macular Degeneration

    PubMed Central

    Gelfand, Bradley D.; Ambati, Jayakrishna

    2016-01-01

    Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

  4. Highly penetrant alleles in age-related macular degeneration.

    PubMed

    den Hollander, Anneke I; de Jong, Eiko K

    2014-11-06

    Age-related macular degeneration (AMD) is a complex disease caused by a combination of genetic and environmental factors. Genome-wide association studies have identified several common genetic variants associated with AMD, which together account for 15%-65% of the heritability of AMD. Multiple hypotheses to clarify the unexplained portion of genetic variance have been proposed, such as gene-gene interactions, gene-environment interactions, structural variations, epigenetics, and rare variants. Several studies support a role for rare variants with large effect sizes in the pathogenesis of AMD. In this work, we review the methods that can be used to detect rare variants in common diseases, as well as the recent progress that has been made in the identification of rare variants in AMD. In addition, the relevance of these rare variants for diagnosis, prognosis, and treatment of AMD is highlighted.

  5. American Macular Degeneration Foundation

    MedlinePlus

    ... vs. Treatment Eylea Injection Treatment Amsler Chart to Test Your Sight Good Food Recommended Supplements Lutein Zeaxanthin Ten Habits for Eye Health Technology for Low Vision Depression and AMD Service Providers ...

  6. [Progression of treatment and researches in dry age related macular degeneration].

    PubMed

    Zhang, Kaiyan; Tang, Shibo

    2015-03-01

    Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

  7. [Serum antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD) treated with transpupillary thermotherapy (TTT) alone and with transpupillary thermotherapy (TTT) combined with injection of triamcinolone acetonide (sTTA) under posterior Tenon's capsule].

    PubMed

    Kubicka-Trzaska, Agnieszka; Wilańska, Joanna

    2011-01-01

    To assess serum level changes of antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD), treated with transpupillary thermotherapy (TTT) alone and with TTT combined with injection of triamcinolone acetonide (sTTA) under posterior Tenon's capsule and to compare the efficacy of TTT and TTT+sTTA. The purpose of the study was also to estimate if serum ARA may act as the biomarker of AMD. This prospective study comprised 46 patients (46 eyes) with exudative AMD. Patients were assigned into: group I (n = 24) received TTT alone and group II (n = 20) received TTT with sTTA. Follow-up was at 3, 6, 9 and 12 months, when best-corrected visual acuity (BCVA), Amsler grid-test, intraocular pressure (IOP), fluorescein angiography (FA) and central retinal thickness (CRT) by optical coherence tomography (OCT) were assessed. In all patients serum ARA was determined using indirect immunofluorescence (IIF) method on normal monkey retina as antigens substrate and FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody. Baseline serum ARA titres in group I ranged from 1: 40 to 1: 5120 and in group II--1: 40 to 1: 1280 (p = 0.1). In control group serum ARA was present in 46.4% of sera in titres from 1: 10 to 1: 40. These differences were statistcally significant (p < 0.001). Nine fluorescence patterns of ARA were detected by IIF method in both groups of AMD patients, while control sera showed only three types of reaction. Statistically significant correlation was found between CNV size, CRT and serum ARA titres in both groups of patients (p < 0.01). In a follow-up period decreasing serum ARA titres were noted, specially for subjects treated with combined therapy, however it was not statistically significant at 3, 6 and 9 months while achieved significance (p < 0.01) at month 12. BCVA improvement or stabilization was observed in 64% of eyes in group I and in 75%--in group II (p = 0.1). No leakage on FA was found in 66.7% and 70

  8. Age-related macular degeneration: Complement in action.

    PubMed

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  9. The genetics of age-related macular degeneration.

    PubMed

    Gorin, M B; Breitner, J C; De Jong, P T; Hageman, G S; Klaver, C C; Kuehn, M H; Seddon, J M

    1999-11-03

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  10. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2014-12-18

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD.

  11. Race, iris color, and age-related macular degeneration.

    PubMed

    Frank, R N; Puklin, J E; Stock, C; Canter, L A

    2000-01-01

    While most observers agree that age-related macular degeneration (AMD) is much more common in white persons than in persons of black African ancestry, the influence of iris color has been more controversial. We reexamined relationships between race, iris color, and AMD in a series of patients from our retina clinic. We evaluated, in masked fashion, stereoscopic photographs of the retinas and irides in 306 sequential patients 60 years of age or older from our retina clinics. Four readers judged whether AMD was present, absent, or questionable in the retinal photographs and labeled iris color as blue, hazel, or brown. Presence or absence of AMD and presence and severity of the various macular lesions were determined by "majority vote" of the readers. We evaluated inter-rater agreement using the kappa statistic. We compared the prevalence of AMD and of specific AMD lesions as a function of race, sex, and iris color by contingency table analysis. The kappa statistic showed good inter-observer agreement, being 0.466 (P < 10(-6)) for definite or questionable AMD and ranging from 0.185 to 0.522 (P = 0.0047 to P < 10(-6)) for most lesions. We found significantly more AMD in white patients than in black patients (X2 = 27.54, P < 10(-4)). There was no significant difference in AMD prevalence by sex. In white patients, AMD was significantly more prevalent in individuals with blue or hazel irides than in those with brown irides (X2 = 15.04, P = .02). We confirm previous findings of a higher prevalence of AMD in white persons than in black persons. We also agree with those observers who claim that white subjects with light-colored irides have a higher prevalence of AMD than those with dark-colored irides. We suggest that differences in the association between iris pigmentation and AMD in different studies using different research methods may reflect genetic difference in the groups being studied.

  12. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2014-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search strategy We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE and LILACS on 30 April 2009 and the WHO International Clinical Trials Registry Platform on 11 May 2009. We searched reference lists and the Science Citation Index. There were no language or date restrictions in the search for trials. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and

  13. Update on geographic atrophy in age-related macular degeneration.

    PubMed

    Biarnés, Marc; Monés, Jordi; Alonso, Jordi; Arias, Luis

    2011-07-01

    Age-related macular degeneration (AMD) is the main cause of legal blindness in older patients in developed countries, and geographic atrophy (GA) represents the advanced form of dry AMD. Although it accounts for one third of the cases of late AMD and is responsible for 20% of the cases of severe visual loss due to the disorder. GA currently lacks effective treatment, whereas antiangiogenic therapies have been shown to be successful in managing choroidal neovascularization, the other form of late AMD. Recent advances in GA epidemiology, etiology, genetics, and imaging techniques have renewed the interest in this entity, which is a cause of progressive visual loss even in treated patients with neovascular AMD. This knowledge has triggered many clinical trials targeting different molecules shown to be associated with the disease, and it is hoped that this research will translate into effective drugs for GA in the near future.

  14. [Molecular genetic basis of age-related macular degeneration].

    PubMed

    Boĭko, É V; Churashov, S V; Kamilova, T A

    2013-01-01

    Visual loss due to age-related macular degeneration (AMD) is caused by one or both forms of advanced disease: "wet" (neovascular) or "dry" (geographic atrophy). Immune system plays a central role in pathogenesis and progression of both AMD forms. Main genetic polymorphisms associated with risk of AMD development and progression were found to be genes that regulate inflammation especially in complement factor H gen (1q31 locus) and 10q26 locus (PLEKHAI/ARMS2/HTRA1). Association of response to treatment and genotype was shown in patients with AMD. Complete characterization of both common and rare alleles that influence AMD risk is necessary for accurate determination of individual genetic risk as well as identification of new targets for therapeutic intervention.

  15. Gene-Diet Interactions in Age-Related Macular Degeneration.

    PubMed

    Rowan, Sheldon; Taylor, Allen

    2016-01-01

    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 is the only available treatment option for the dry form of the disease known to slow progression of AMD. Despite an excellent understanding of genes and nutrition in AMD, there is remarkably little known about gene-diet interactions that may identify efficacious approaches to treat individuals. This review will summarize our current understanding of gene-diet interactions in AMD with a focus on animal models and human epidemiological studies.

  16. Mechanisms of age-related macular degeneration and therapeutic opportunities.

    PubMed

    van Lookeren Campagne, Menno; LeCouter, Jennifer; Yaspan, Brian L; Ye, Weilan

    2014-01-01

    As the age of the population increases in many nations, age-related degenerative diseases pose significant socioeconomic challenges. One of the key degenerative diseases that compromise quality of life is age-related macular degeneration (AMD). AMD is a multi-faceted condition that affects the central retina, which ultimately leads to blindness in millions of people worldwide. The pathophysiology and risk factors for AMD are complex, and the symptoms manifest in multiple related but distinct forms. The ability to develop effective treatments for AMD will depend on a thorough understanding of the underlying pathophysiology, risk factors, and driver molecular pathways, as well as the ability to develop useful animal models. This review provides an overview of the aforementioned aspects in AMD.

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

    PubMed Central

    Ebrahimi, Katayoon B.; Handa, James T.

    2011-01-01

    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. PMID:21822496

  18. [Chronic central serous chorioretinopathy (cCSC): differential diagnosis to choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD)].

    PubMed

    Inhoffen, W; Ziemssen, F; Bartz-Schmidt, K U

    2012-09-01

    Central neurosensory detachments (NSD) with time-dependent height constitute a disease called central serous chorioretinopathy (CSC), if not arising from uveitis, choroidal neovascularisations (CNV) or leaking retinal vessels. In 10 % of these patients, CSC develops into a chronic disease with recurrent NSD, atrophy of photoreceptors and severe drop in visual acuity. This review article summarises recent progress in understanding this disease and its appearance in funduscopy, FLA, ICG, OCT, autofluorescence as well as its progress, therapy and possible development into secondary CNV. The provided examples illustrate the progression of acute CSC into chronic CSC and with CNV over years. The different appearance of polypoidal choroidal vasculopathy (PCV) in ICG and some of the signs of atypical chronic CSC are discussed. To distinguish between cCSC and wet AMD--both exhibiting leakage in FLA--typical signs are helpful, e.g., "gravitational tracks", retinal precipitates and missing drusen. However, in small lesions, it may be difficult or almost impossible to ensure the correct diagnosis of the underlying disease. The same holds for occult and classic secondary CNV in cCSC vs. CNV in AMD, where photodynamic therapy (PDT) can be successful only in cCSC-CNV and in cCSC without CNV. Corticosteroids often lead to further impairment, even in cases of atypical cCSC, when frequently misdiagnosed as uveitis. As a duration of NSD of more than 4 months is suspected to induce an impairment of photoreceptors, regular examinations are necessary not only in chronic CSC but also after acute CSC (as this form can develop into chronic CSC), while effective therapies are available to resolve the NSD (PDT, anti-VEGF).

  19. Age related macular degeneration and visual disability.

    PubMed

    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

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

    PubMed

    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.

  1. Rehabilitation Approaches in Macular Degeneration Patients

    PubMed Central

    Maniglia, Marcello; Cottereau, Benoit R.; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient’s visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients. PMID:28082876

  2. Rehabilitation Approaches in Macular Degeneration Patients.

    PubMed

    Maniglia, Marcello; Cottereau, Benoit R; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient's quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient's visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients.

  3. The role of epigenetics in age-related macular degeneration.

    PubMed

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  4. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  5. Wearable diagnostic system for age-related macular degeneration.

    PubMed

    Mohaghegh, N; Zadeh, E Ghafar; Magierowski, S

    2016-08-01

    This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

  6. Ocular surface temperature in age-related macular degeneration.

    PubMed

    Sodi, Andrea; Matteoli, Sara; Giacomelli, Giovanni; Finocchio, Lucia; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    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.

  7. Ocular Surface Temperature in Age-Related Macular Degeneration

    PubMed Central

    Sodi, Andrea; Giacomelli, Giovanni; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    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. PMID:25436140

  8. Diminishing risk for age related macular degeneration with nutrition: A current view

    USDA-ARS?s Scientific Manuscript database

    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...

  9. A Qualitative Analysis of Reading Rehabilitation of Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Feely, Mary; Vetere, Arlene; Myers, Lynn B.

    2007-01-01

    One of the most prevalent visual impairments of people aged 60 and older is age-related macular degeneration (AMD), which ranks third globally as a cause of visual impairment (World Health Organization, 2006). The purpose of this study was to conduct a tentative subjective assessment of eccentric viewing by persons with AMD. The authors recruited…

  10. Vitamin E supplementation and macular degeneration: randomised controlled trial

    PubMed Central

    Taylor, Hugh R; Tikellis, Gabriella; Robman, Luba D; McCarty, Catherine A; McNeil, John J

    2002-01-01

    Objective To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD). Design Prospective randomised placebo controlled clinical trial. Setting An urban study centre in a residential area supervised by university research staff. Participants 1193 healthy volunteers aged between 55 and 80 years; 73% completed the trial on full protocol. Interventions Vitamin E 500 IU or placebo daily for four years. Main outcome measures Primary outcome: development of early age related macular degeneration in retinal photographs. Other measures included alternative definitions of age related macular degeneration, progression, changes in component features, visual acuity, and visual function Results The incidence of early age related macular degeneration (early AMD 3) was 8.6% in those receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95% confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus 0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in secondary outcomes. Conclusion Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration. What is already known on this topicAge related macular degeneration is the leading cause of loss of vision and blindness in elderly people; for people aged ⩾90 years, two out of every three will be affected and one in four will become blindCurrently, there are no methods of prevention or treatment in most cases, though a third of cases are due to cigarette smokingAntioxidant vitamins have been suggested as a possible preventionWhat this study addsDaily supplementation with 500 mg vitamin E for four years did not alter the incidence or progression of AMD PMID:12098721

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. [Cell Transplantation in Age-related Macular Degeneration].

    PubMed

    Kirchhof, Bernd

    2017-09-01

    Robert Machemer offers a surgical approach to age-related macular degeneration with his retinal rotation. There is already considerable experimental and clinical knowledge available in Europe and the US on transplantation techniques for age-related macular degeneration. On average, initial visual acuity can be preserved. When photodynamic therapy was standard for exudative AMD, transplantation was superior. Photodynamic therapy could not stop, but was instead able to slow down visual loss. Currently, VEGF-blocker therapy has priority, because the visual acuity can be improved. However, this advantage does not last much longer than two years. Therefore, in the future, transplantation with new cells and less surgical risk may be reconsidered. At present, homologous RPE stem cells show promising results. They may be delivered as "sheets" or as single cells. For dry AMD only, a prophylactic approach seems reasonable, because, thus far, we are unable to reverse the atrophy on the retinal side. Georg Thieme Verlag KG Stuttgart · New York.

  13. Genetics of immunological and inflammatory components in age-related macular degeneration.

    PubMed

    Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao

    2012-02-01

    Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch's membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD.

  14. Solar radiation and age-related macular degeneration.

    PubMed

    Young, R W

    1988-01-01

    Age-related macular degeneration (AMD) involves a progressive impairment of the outer layers in the center of the retina. Experimental studies have demonstrated that bright light preferentially damages precisely the region that degenerates in AMD. The evidence that solar radiation is responsible for some of the deteriorative changes that lead to AMD is examined in this review. In the primate eye, the high-energy portion of the solar spectrum is most hazardous to retinal molecules, with damaging effects increasing as photon energy rises. This action spectrum is explicable by the quantum laws which describe the interaction of radiation with matter. High-energy visible and ultraviolet photons can produce molecular damage by a photochemical mechanism. The lesion is exacerbated by oxygen, which initiates free-radical chain reactions (photodynamic effects). Melanin exerts a protective effect against damage from sunlight. In the human retina, documented lesions from solar radiation range from the acute effects of sun-gazing to injuries resulting from prolonged periods of exposure in brightly illuminated environments. The damage occurs in the same region that degenerates in AMD. A cataractous lens and ocular melanin both protect the retina against AMD, as predicted by the radiation hypothesis. Identification of an environmental factor that evidently plays a role in the etiology of AMD provides the basis for a program of preventive medicine.

  15. Targeting MAPK Signaling in Age-Related Macular Degeneration

    PubMed Central

    Kyosseva, Svetlana V.

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease. PMID:27385915

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

    PubMed Central

    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

  17. [Pathogenesis of age-related macular degeneration].

    PubMed

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  18. Genetics Home Reference: age-related macular degeneration

    MedlinePlus

    ... Health Conditions age-related macular degeneration age-related macular degeneration Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Age-related macular degeneration is an eye disease that is a leading ...

  19. Therapeutic Modalities of Exudative Age-related Macular Degeneration

    PubMed Central

    Mavija, Milka; Alimanovic, Emina; Jaksic, Vesna; Kasumovic, Sanja Sefic; Cekic, Sonja; Stamenkovic, Miroslav

    2014-01-01

    Introduction: Age-related macular degeneration (AMD) is a leading cause of irreversible serious vision damage in persons over 50 years of age. In treating AMD many medicaments are applied such as inhibitors of vascular endothelial growth factor (VEGF), have been very carefully included over the last few years after a series of study research. Aims: To analyze the past methods of treatment, discuss emerging therapies which could advance the treatment of exudative AMD. The past anti-VEGF therapies require frequent repetitions of administration, with uncertain visual acuity recovery, as not all patients react to anti-VEGF therapy. Consequently, there is a need to find out additional therapies which could improve the treatment of exudative AMD. The real aim in the treating of AMD is to prevent CNV development. Methods: A survey of the current clinical research and results in the field of the present and future treatments of exudative AMD. Results: There are many areas of research into new methods of the exudative AMD treatment. Conclusion: The future therapies for exudative AMD treatment have a potential not only to reduce the frequency of administration and follow-up visits, but also to improve effects of treatment by targeting additional ways of CNV development, increasing the aptitude of target binding and extending durability of treatment. PMID:25568535

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

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT 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. PMID:26035859

  1. Fundus autofluorescence in exudative age-related macular degeneration.

    PubMed

    Peng, Q; Dong, Y; Zhao, P Q

    2013-12-02

    The aim of this study was to investigate the characteristics of fundus autofluorescence (FAF) in patients with wet (exudative) age-related macular degeneration (AMD). Color fundus photographs, fundus fluorescein angiograms, indocyanine green angiograms, and FAF images were obtained from 61 patients (72 eyes) with exudative AMD. The FAF results for different patterns of exudative AMD were compared to those revealed by other fundus images. Of the 72 eyes evaluated, which were classified into three patterns based on the results of fundus fluorescein angiography, 68 had abnormal FAF. Forty-six eyes (63.9%) had classic wet AMD with abnormal FAF. Among these, 10 exhibited a slightly decreased FAF with near-normal or background FAF signal at the center of the lesion area; 36 demonstrated not only decreased FAF at the center of the lesion but also an increased FAF signal toward the lesion edge. Sixteen eyes (22.2%) had occult wet AMD, of which 12 exhibited heterogeneous fluorescence at the lesion site; 4 yielded normal FAF images. Ten eyes (13.9%) had a mixed pattern of wet AMD with abnormal FAF. FAF imaging suggested that the areas of blood and exudates decreased; however, fluorescence angiography revealed that lesions with hyperfluorescence had background or slightly increased FAF. These results showed that various patterns of wet AMD exhibit different autofluorescence characteristics. These represent the functional and metabolic features of retinal pigment epithelial cells. Therefore, FAF can be used to monitor disease development and evaluate the severity and prognosis of AMD.

  2. [Effects of diabetes mellitus on the occurrence of age-related macular degeneration].

    PubMed

    Li, Xia; Wang, Yu-sheng

    2011-03-01

    Diabetes mellitus causing long term disturbed glucose metabolism could result in tissue injury and multiple complications. According to recent studies, diabetes mellitus might be regarded as one of the risk factors of age related macular degeneration (AMD). Diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. By studying epidemiological investigation and basic research on this subject comprehensively, it is required to review the correlation between diabetes mellitus and AMD.

  3. Epidemiology and quality of life of patients with age-related macular degeneration.

    PubMed

    Synek, Svatopluk; Vojniković, Bozo; Pahor, Dana

    2010-04-01

    It is well known that age-related macular degeneration (AMD), besides glaucoma and diabetic retinopathy, represents a major cause of low vision and blindness throughout the world. In this study, specific causal factors of AMD are analyzed, emphasizing the causal role and effects of sunlight, no matter which part of its spectrum, in a longer exposition through life. The accent is also put on the influence of lifestyle as well as vitamin and antioxidants supplementation in development or prevention of AMD.

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

    PubMed

    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] < 0.001) and noncentral geographic atrophy (GA; P[static and flicker] < 0.001) had significant reductions in static and 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.

  5. Dry age-related macular degeneration: A currently unmet clinical need

    PubMed Central

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-01-01

    Summary Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need. PMID:25343081

  6. Dry age-related macular degeneration: A currently unmet clinical need.

    PubMed

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-08-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.

  7. Perceptual learning in patients with macular degeneration.

    PubMed

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rühle, Sabine; Greenlee, Mark W

    2014-01-01

    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 = 0.001) 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 = 0.014). 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 = 0.014, 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.

  8. Perceptual learning in patients with macular degeneration

    PubMed Central

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rühle, Sabine; Greenlee, Mark W.

    2014-01-01

    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 = 0.001) 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 = 0.014). 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 = 0.014, 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. PMID:25368597

  9. Nutritional modulation of age-related macular degeneration.

    PubMed

    Weikel, Karen A; Chiu, Chung-Jung; Taylor, Allen

    2012-08-01

    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 with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro- and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/week of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available.

  10. Nutritional Modulation of Age-Related Macular Degeneration

    PubMed Central

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    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 with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

  11. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2013-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), 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). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the

  12. CYP4F2 (rs2108622) Gene Polymorphism Association with Age-Related Macular Degeneration

    PubMed Central

    Kriauciuniene, Loresa; Balciuniene, Vilma Jurate; Buteikiene, Dovile; Miniauskiene, Goda; Liutkeviciene, Rasa

    2016-01-01

    Background. Age-related macular degeneration is the leading cause of blindness in elderly individuals where aetiology and pathophysiology of age-related macular degeneration are not absolutely clear. Purpose. To determine the frequency of the genotype of rs2108622 in patients with early and exudative age-related macular degeneration. Methods. The study enrolled 190 patients with early age-related macular degeneration, 181 patients with exudative age-related macular degeneration (eAMD), and a random sample of 210 subjects from the general population (control group). The genotyping of rs2108622 was carried out using the real-time polymerase chain reaction method. Results. The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the early AMD group, the eAMD group, and the control group. The CYP4F2 (1347C>T) T/T genotype was more frequent in males with eAMD compared to females (10.2% versus 0.8%; p = 0.0052); also T/T genotype was less frequently present in eAMD females compared to healthy control females (0.8% versus 6.2%; p = 0.027). Conclusion. Rs2108622 gene polymorphism had no predominant effect on the development of early AMD and eAMD. The T/T genotype was more frequent in males with eAMD compared to females and less frequently present in eAMD females compared to healthy females. PMID:27652291

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

    PubMed Central

    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

  14. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... To Protect Against Macular Degeneration Jan 27, 2016 Eye Exercises May Improve Vision Around Blind Spot Sep 29, 2015 Could Stem Cells Cure Blindness Caused by Macular Degeneration? Sep 29, 2015 Fighting the Signs of Aging? Don’t Forget the Eyes Sep 11, ... Follow The Academy Professionals: Education ...

  15. Treatment of macular degeneration, according to Bangerter.

    PubMed

    Teichmann, K D

    1997-10-30

    Age-related macular degeneration (AMD) is a common cause of visual loss among elderly patients. Although some risk factors have been determined, the ultimate cause of the disease is not known. For a long time, therapeutic nihilism has been the rule among ophthalmologists confronted with such patients. Bangerter has not shared this attitude, especially since the time that he incidentally discovered, more than 40 years ago, the beneficial effects of radiotherapy, in discouraging the growth of new vessels at the posterior pole of the eye. A variety of approaches are combined and used by Bangerter in the treatment of the different types of AMD, including retrobulbar injections of either vasodilating medications (in the dry - or atrophic - type) or corticosteroids (in the wet - or exudative - type), general medical measures aimed at improving metabolic and vascular functions such as supplementation with trace elements, antioxidants, and vitamins; ozone therapy; advice to increase physical fitness, improve nutrition, and abstain from smoking; and protection from excessive light exposure. Being convinced of the usefulness of his type of combination treatment, he has always rejected undertaking controlled clinical trials, of only single aspects of the therapy, as unethical and invalid. For this reason, scientific journals have not proven cooperative in several attempts at publishing his results, as collected in retrospective surveys. Recently, however, some of the several approaches combined by Bangerter in treating AMD have been pronounced effective by other investigators. We present here an overview of his treatment approaches, as few people are aware of them, to clear up misconceptions and to set records straight.

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

    PubMed Central

    2016-01-01

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

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

    PubMed

    Das, Undurti N

    2016-10-01

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

  18. Effects of Age-Related Macular Degeneration on Postural Sway

    PubMed Central

    Chatard, Hortense; Tepenier, Laure; Jankowski, Olivier; Aussems, Antoine; Allieta, Alain; Beydoun, Talal; Salah, Sawsen; Bucci, Maria P.

    2017-01-01

    Purpose: To compare the impact of unilateral vs. bilateral age-related macular degeneration (AMD) on postural sway, and the influence of different visual conditions. The hypothesis of our study was that the impact of AMD will be different between unilateral and bilateral AMD subjects compared to age-matched healthy elderly. Methods: Postural stability was measured with a platform (TechnoConcept®) in 10 elderly unilateral AMD subjects (mean age: 71.1 ± 4.6 years), 10 elderly bilateral AMD subjects (mean age: 70.8 ± 6.1 years), and 10 healthy age-matched control subjects (mean age: 69.8 ± 6.3 years). Four visual conditions were tested: both eyes viewing condition (BEV), dominant eye viewing (DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the surface area, the length, the mean speed, the anteroposterior (AP), and mediolateral (ML) displacement of the center of pressure (CoP). Results: Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest that ADM subjects could have poor postural adaptive mechanisms leading to increase their postural instability. Further studies will aim to improve knowledge on such issue and to develop reeducation techniques in these patients. PMID:28408876

  19. Sunlight exposure, antioxidants, and age-related macular degeneration.

    PubMed

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

    2008-10-01

    To examine the association of sunlight exposure and antioxidant level with age-related macular degeneration (AMD). Four thousand seven hundred fifty-three participants aged 65 years or older in the European Eye Study underwent fundus photography, were interviewed for adult lifetime sunlight exposure, and gave blood for antioxidant analysis. Blue light exposure was estimated by combining meteorologic and questionnaire data. Data on sunlight exposure and antioxidants were available in 101 individuals with neovascular AMD, 2182 with early AMD, and 2117 controls. No association was found between blue light exposure and neovascular or early AMD. Significant associations were found between blue light exposure and neovascular AMD in individuals in the quartile of lowest antioxidant level-vitamin C, zeaxanthin, vitamin E, and dietary zinc-with an odds ratio of about 1.4 for 1 standard deviation unit increase in blue light exposure. Higher odds ratios for blue light were observed with combined low antioxidant levels, especially vitamin C, zeaxanthin, and vitamin E (odds ratio, 3.7; 95% confidence interval, 1.6-8.9), which were also associated with early stages of AMD. Although it is not possible to establish causality between sunlight exposure and neovascular AMD, our results suggest that people in the general population should use ocular protection and follow dietary recommendations for the key antioxidant nutrients.

  20. Reticular pseudodrusen in age-related macular degeneration.

    PubMed

    Hogg, Ruth Esther

    2014-08-01

    Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

  1. Recent developments in age-related macular degeneration: a review.

    PubMed

    Al-Zamil, Waseem M; Yassin, Sanaa A

    2017-01-01

    Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease "wet AMD" into a more favorable outcome.

  2. Resonance Raman Measurement of Macular Carotenoids in Normal Subjects and in Age-related Macular Degeneration Patients

    PubMed Central

    Bernstein, Paul S.; Zhao, Da-You; Wintch, Steven W.; Ermakov, Igor V.; McClane, Robert W.; Gellermann, Werner

    2011-01-01

    Purpose Dietary carotenoids lutein and zeaxanthin may play a protective role against visual loss from age-related macular degeneration (AMD) through antioxidant and light screening mechanisms. We used a novel noninvasive objective method to quantify lutein and zeaxanthin in the human macula using resonance Raman spectroscopy and compared macular pigment levels in AMD and normal subjects. Design Observational study of an ophthalmology clinic-based population. Participants and Controls Ninety-three AMD eyes from 63 patients and 220 normal eyes from 138 subjects. Methods Macular carotenoid levels were quantified by illuminating the macula with a low-power argon laser spot and measuring Raman backscattered light using a spectrograph. This technique is sensitive, specific, and repeatable even in subjects with significant macular pathologic features. Main Outcome Measure Raman signal intensity at 1525 cm−1 generated by the carbon–carbon double-bond vibrations of lutein and zeaxanthin. Results Carotenoid Raman signal intensity declined with age in normal eyes (P < 0.001). Average levels of lutein and zeaxanthin were 32% lower in AMD eyes versus normal elderly control eyes as long as the subjects were not consuming high-dose lutein supplements (P = 0.001). Patients who had begun to consume supplements containing high doses of lutein (≥4 mg/day) regularly after their initial diagnosis of AMD had average macular pigment levels that were in the normal range (P = 0.829) and that were significantly higher than in AMD patients not consuming these supplements (P = 0.038). Conclusions These findings are consistent with the hypothesis that low levels of lutein and zeaxanthin in the human macula may represent a pathogenic risk factor for the development of AMD. Resonance Raman measurement of macular carotenoid pigments could play an important role in facilitating large-scale prospective clinical studies of lutein and zeaxanthin protection against AMD, and this technology may

  3. The burden of age-related macular degeneration.

    PubMed

    Schmier, Jordana K; Jones, Mechelle L; Halpern, Michael T

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, both those associated with ophthalmic care and those associated with other care, have been conducted and have identified increased medical care associated with AMD. Direct non-medical costs include the cost for vision aids; while these costs may be substantial, they are difficult to quantify as no comprehensive sources track the distribution or use of vision aids. Because AMD is uncommon among people of working age, there is less concern regarding the impact of indirect (workplace) costs among AMD patients. However, indirect costs are incurred by caregivers who leave the workforce early or change their work patterns in order to provide assistance to AMD patients; the magnitude of caregiver-related costs is unknown. The cost effectiveness of some interventions for AMD has been explored. Supplementation with zinc and antioxidants for non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY and is considered cost effective. Studies suggest that laser photocoagulation is cost effective but that photodynamic therapy with verteporfin appears to be cost effective only among patients with good visual acuity at baseline or when models extend longer than 5 years. Further research is needed to integrate the information on various components of AMD-related costs into a comprehensive burden of illness estimate and to evaluate basic utility assumptions in existing models.

  4. Autophagy regulating kinases as potential therapeutic targets for age-related macular degeneration.

    PubMed

    Kaarniranta, Kai; Kauppinen, Anu; Blasiak, Janusz; Salminen, Antero

    2012-11-01

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly in the developed countries. The number of AMD patients will double during the next decades due to increasing number of aged people. Chronic oxidative stress, inflammation and accumulation of protein-rich deposits both in the retinal pigment epithelium lysosomes and under the retinal pigment epithelium herald the onset of AMD. The disease can be divided into dry and wet AMD forms. The dry form of the disease is more prevalent accounting for up to 90% of all cases. Continued intraocular injections are the current treatment strategy to prevent progression of wet AMD. It is a major challenge to develop new drugs that could prevent or at least ease the symptoms of the increasing population of AMD patients. Since AMD pathology is clearly associated with accumulated protein deposits, the autophagy clearance system might represent a potential future therapeutic target for AMD as is thoroughly discussed here.

  5. [Urgent action needed to raise public awareness of age-related macular degeneration in China].

    PubMed

    Chen, You-xin

    2009-05-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The impact of AMD to the economics, society and the patients are huge. However, the awareness of AMD is alarmingly low. Even in developed countries, the awareness of AMD is below 30%. In terms of the risk factors of AMD, the awareness is also quite low, e.g., only 32% were aware of the causal link between smoking and AMD. Although cataract is the leading cause of the blindness in China, as the economic and social progress, as the coming of the aging society, as people pursuing higher quality of life, AMD will become a unignoring public health problem. Thus, it is urgent to take action now to increase the public awareness of AMD.

  6. Anxiety and depression in patients with advanced macular degeneration: current perspectives

    PubMed Central

    Cimarolli, Verena R; Casten, Robin J; Rovner, Barry W; Heyl, Vera; Sörensen, Silvia; Horowitz, Amy

    2016-01-01

    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 screen for these two prevalent mental health problems and how to facilitate appropriate treatment for patients with AMD. PMID:26766899

  7. Age-related macular degeneration and the role of the complement system.

    PubMed

    McHarg, Selina; Clark, Simon J; Day, Anthony J; Bishop, Paul N

    2015-09-01

    Age-related macular degeneration (AMD) is a leading cause of visual impairment. It is characterised by damage to a tissue complex composed of the retinal pigment epithelium, Bruch's membrane and choriocapillaris. In early AMD extracellular debris including drusen accumulates in Bruch's membrane and then in late AMD geographic atrophy and/or neovascularisation develop. Variants in genes encoding components of the alternative pathway of the complement cascade have a major influence on AMD risk, especially at the RCA locus on chromosome 1, which contains CFH and the CFHR genes. Immunohistochemical studies have demonstrated complement components in unaffected and AMD macular tissue. Whilst other factors, including oxidative stress, play important roles in AMD pathogenesis, evidence for the central role played by complement dysregulation is discussed in this review.

  8. Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration

    PubMed Central

    Shiragami, Chieko; Miyake, Masahiro; Fujiwara, Atsushi; Morizane, Yuki; Tsujikawa, Akitaka; Yamashita, Ayana; Shiraga, Fumio

    2017-01-01

    Abstract Background: To evaluate the efficacy and safety of topical isopropyl unoprostone (IU) in treating macular atrophy in age-related macular degeneration (AMD) patients. Methods: Fifty-two AMD patients with macular atrophy were included and randomly assigned (1:1) to the treatment (topical 0.15% IU) or placebo group. Subjects used study eye drops 3 times a day for 54 weeks. The macular atrophy was documented on fundus autofluorescence photographs and measured using RegionFinder. The enlargement rate of macular atrophy and the changes in visual acuity were examined statistically between baseline and 54 weeks. Results: Forty-eight subjects were included in the analyses because 4 subjects withdrew from the study. The differences between the IU and placebo groups in mean and median area of macular atrophy were not statistically significant at baseline. The baseline median lesion size of macular atrophy was 2.33 mm2 in the IU group and 1.63 mm2 in the placebo group (P = 0.51). The intergroup difference in the enlargement ratio of macular atrophy (21 ± 15% in the IU group and 111 ± 96% in the placebo group) was statistically significant (P < 0.001). Additionally, visual acuity tended to improve over baseline in the IU group. No serious adverse events were observed. Conclusions: Topical IU therapy is safe and effective for treating macular atrophy in AMD patients. PMID:28328847

  9. Light and macular degeneration: a biophysical and clinical perspective.

    PubMed

    Mainster, M A

    1987-01-01

    The evidence linking photic retinopathy to ageing macular degeneration (AMD) is compelling but circumstantial. The biophysical foundations of ageing theory are presented, in addition to an analysis of retinal senescence and the potential contributory role of photochemical retinal damage. Although there is pressure to implement clinical therapy for AMD based on laboratory studies of photic retinopathy, there is no evidence at this time that any such therapy is effective. Nonetheless, until the relationship between photic retinopathy and AMD is better understood, it is appropriate for individuals to use ultraviolet and deep blue protective sunglasses in bright environments, particularly if they have reduced ocular pigmentation or if they are aphakes or pseudophakes without an ultraviolet-protective intraocular lens.

  10. Mediated-reality magnification for macular degeneration rehabilitation

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

  12. Emphysema, airflow limitation, and early age-related macular degeneration.

    PubMed

    Klein, Ronald; Knudtson, Michael D; Klein, Barbara E K; Wong, Tien Y; Cotch, Mary Frances; Barr, Graham

    2010-04-01

    To describe the associations of lung function and emphysema, measured with spirometry and computed tomography (CT), with early age-related macular degeneration (AMD) in a sample of white, black, Hispanic, and Chinese subjects. Three thousand three hundred ninety-nine persons aged 45 to 84 years residing in 6 US communities participated in a period cross-sectional study. Age-related macular degeneration was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in 1 second (FEV(1)) and FEV(1) to forced vital capacity (FVC) ratio were measured at the third or fourth MESA examination. Percent emphysema was measured from cardiac CT scans at baseline. Apical and basilar lung segments were defined as the cephalad or caudal regions of the lung on the cardiac CT scan. Logistic regression models were used to examine the association of lung function and structure with AMD, controlling for age, sex, and other factors. The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV(1) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.58-1.15; P = .25), FEV(1):FVC ratio (OR, 0.92; 95% CI, 0.76-1.12; P = .43), percent emphysema (OR, 1.13; 95% CI, 0.91-1.40; P = .26), and apical-basilar difference in percent emphysema (OR, 1.14; 95% CI, 0.95-1.37; P = .17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among those who ever smoked (OR, 1.28; 95% CI, 1.02-1.60; P = .03). Associations were not modified by race/ethnicity. Lung function and emphysema on CT scan were not cross-sectionally associated with AMD; this might be explained by the relatively low smoking exposure in this cohort.

  13. Updates on the Epidemiology of Age-Related Macular Degeneration.

    PubMed

    Jonas, Jost B; Cheung, Chui Ming Gemmy; Panda-Jonas, Songhomitra

    2017-09-14

    This meta-analysis reports on current estimates of the prevalence of age-related macular degeneration (AMD) based on a review of recent meta-analyses and literature research. Within an age of 45-85 years, global prevalences of any AMD, early AMD, and late AMD were 8.7% [95% credible interval (CrI), 4.3‒17.4], 8.0% (95% CrI, 4.0‒15.5), and 0.4% (95% CrI, 0.2-0.8). Early AMD was more common in individuals of European ancestry (11.2%) than in Asians (6.8%), whereas prevalence of late AMD did not differ significantly. AMD of any type was less common in individuals of African ancestry. The number of individuals with AMD was estimated to be 196 million (95% CrI, 140‒261) in 2020 and 288 million (95% CrI, 205‒399) in 2040. The worldwide number of persons blind (presenting visual acuity < 3/60) or with moderate to severe vision impairment (MSVI; presenting visual acuity < 6/18 to 3/60 inclusive) due to macular disease in 2010 was 2.1 million [95% uncertainty interval (UI), 1.9‒2.7] individuals out of 32.4 million individuals blind and 6.0 million (95% UI, 5.2‒8.1) persons out of 191 million people with MSVI. Age-standardized prevalence of macular diseases as cause of blindness in adults aged 50+ years worldwide decreased from 0.2% (95% UI, 0.2‒0.2) in 1990 to 0.1% (95% UI, 0.1‒0.2) in 2010; as cause for MSVI, it remained mostly unchanged (1990: 0.4%; 95% UI, 0.3‒0.5; 2010: 0.4%; 95% UI, 0.4‒0.6), with no significant sex difference. In 2015, AMD was the fourth most common cause of blindness globally (in approximately 5.8% of blind individuals) and third most common cause for MSVI (3.9%). These data show the globally increasing importance of AMD. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  14. Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

    PubMed Central

    Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

    2011-01-01

    Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

  15. Fundus Autofluorescence in Age-related Macular Degeneration

    PubMed Central

    Ly, Angelica; Nivison-Smith, Lisa; Assaad, Nagi; Kalloniatis, Michael

    2017-01-01

    ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

  16. Mechanism of inflammation in age-related macular degeneration.

    PubMed

    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.

  17. Recent developments in age-related macular degeneration: a review

    PubMed Central

    Al-Zamil, Waseem M; Yassin, Sanaa A

    2017-01-01

    Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

  18. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    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. Gene therapy for age-related macular degeneration.

    PubMed

    Moore, Nicholas A; Bracha, Peter; Hussain, Rehan M; Morral, Nuria; Ciulla, Thomas A

    2017-10-01

    In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the treatment burden of chronic intravitreal therapy and improve limited visual outcomes associated with 'real world' undertreatment. Areas covered: In this review, the authors assess the evolution of gene therapy for AMD. Adeno-associated virus (AAV) vectors can transduce retinal pigment epithelium; one such early application was a phase I trial of AAV2-delivered pigment epithelium derived factor gene in advanced nAMD. Subsequently, gene therapy for AMD shifted to the investigation of soluble fms-like tyrosine kinase-1 (sFLT-1), an endogenously expressed VEGF inhibitor, binding and neutralizing VEGF-A. After some disappointing results, research has centered on novel vectors, including optimized AAV2, AAV8 and lentivirus, as well as genes encoding other anti-angiogenic proteins, including ranibizumab, aflibercept, angiostatin and endostatin. Also, gene therapy targeting the complement system is being investigated for geographic atrophy due to non-neovascular AMD. Expert opinion: The success of gene therapy for AMD will depend on the selection of the most appropriate therapeutic protein and its level of chronic expression. Future investigations will center on optimizing vector, promoter and delivery methods, and evaluating the risks of the chronic expression of anti-angiogenic or anti-complement proteins.

  20. Complement Factor D in Age-Related Macular Degeneration

    PubMed Central

    Stanton, Chloe M.; Yates, John R.W.; den Hollander, Anneke I.; Seddon, Johanna M.; Swaroop, Anand; Stambolian, Dwight; Fauser, Sascha; Hoyng, Carel; Yu, Yi; Atsuhiro, Kanda; Branham, Kari; Othman, Mohammad; Chen, Wei; Kortvely, Elod; Chalmers, Kevin; Hayward, Caroline; Moore, Anthony T.; Dhillon, Baljean; Ueffing, Marius

    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 binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay. Results. Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females. Conclusions. CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis. PMID:22003108

  1. Systemic complement activation in age-related macular degeneration.

    PubMed

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  2. The role of epigenetics in age-related macular degeneration

    PubMed Central

    Gemenetzi, M; Lotery, A J

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: ‘ocular epigenetic mechanisms', ‘human disease epigenetics', and ‘age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was ‘epigenetics in ocular disease', and to restrict search, we used

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

    PubMed

    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.

  4. Parainflammation, chronic inflammation and age-related macular degeneration

    PubMed Central

    Chen, Mei; Xu, Heping

    2016-01-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

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

    PubMed Central

    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

  6. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), 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 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

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

    PubMed Central

    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

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

    PubMed

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

    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

  9. A twin study on age-related macular degeneration.

    PubMed Central

    Meyers, S M

    1994-01-01

    A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD

  10. Age-related macular degeneration: a guide for the primary care physician.

    PubMed

    Hazin, Ribhi; Freeman, P David; Kahook, Malik Y

    2009-02-01

    Age-related macular degeneration (AMD) is the leading cause of visual loss in Americans over the age of 50 years. AMD often results in profound disability due to the disease destroying the macula, the part of the retina responsible for central visual acuity and color vision. Risk factors for AMD include age greater than 50, female gender, Caucasian race, cigarette smoking, and family history of AMD. African Americans and other racial or ethnic groups can be affected by AMD. Although there is no cure for AMD, early diagnosis and treatment may slow disease progression and minimize irreversible visual dysfunction. Individuals suffering from central vision loss from AMD often retain peripheral vision. These affected individuals can benefit from low vision therapy, visual rehabilitation, or both to maintain or enhance activities of daily living.

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

    PubMed

    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.

  12. Relationships of orientation discrimination threshold and visual acuity with macular lesions in age-related macular degeneration.

    PubMed

    Fu, Haojie; Zhang, Bin; Tong, Jianliang; Bedell, Harold; Zhang, Hecheng; Yang, Yating; Nie, Chaochao; Luo, Yingdong; Liu, Xiaoling

    2017-01-01

    To measure visual acuity and metamorphopsia in patients with age-related macular degeneration (AMD) and to explore their relationship with macular lesions. In this cross-sectional study, a total of 32 normal subjects (32 eyes) and 35 AMD patients (35 eyes) were recruited. They were categorized into 4 groups: normal, dry AMD, non-active wet AMD, and active wet AMD. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol. Metamorphopsia was quantified with the orientation discrimination threshold (ODT). Macular lesions, including drusen, sub-retinal fluid (SRF), intra-retinal fluid (IRF), pigmented epithelium detachment (PED), and scarring, were identified with spectral-domain optical coherence tomography (SD-OCT). A linear regression model was established to identify the relationships between the functional and structural changes. BCVA progressively worsened across the normal, dry AMD, non-active wet AMD, and active wet AMD groups (P < 0.001), and ODT increased across the groups (P < 0.001). The correlation between BCVA and ODT varied among the groups. The partial correlation between BCVA and ODT was -0.61 (P < 0.001). Linear regression showed that ODT significantly depended on IRF (β = 0.61, P < 0.001), SRF (β = 0.34, P = 0.003), and scarring (β = 0.26, P = 0.050), while BCVA significantly depended only on scarring (β = -0.52, P < 0.001), and IRF (β = -0.36, P = 0.016). From dry AMD to active wet AMD, BCVA gradually worsened while ODT increased. The correlation between BCVA and ODT varied among these groups, indicating that AMD lesions affect them differently. ODT and BCVA should be used concurrently for better monitoring of the disease.

  13. Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration.

    PubMed

    Robman, Luba; Mahdi, Olaimatu; McCarty, Catherine; Dimitrov, Peter; Tikellis, Gabriella; McNeil, John; Byrne, Gerald; Taylor, Hugh; Guymer, Robyn

    2005-06-01

    Recent studies have found an association between exposure to Chlamydia pneumoniae infection and risk of age-related macular degeneration (AMD). To assess a potential risk of AMD progression posed by exposure to C. pneumoniae, the authors reexamined Australian residents in 2001-2002 who were aged 51-89 years with early AMD at baseline (1992-1995). Examination included macular photography and an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. AMD progression was assessed quantitatively, using both coarse and fine progression steps following an international classification for AMD grading, and also qualitatively, by side-by-side comparison of baseline and follow-up macular photographs. Serologic data were available for 246 of 254 (97%) subjects. AMD progression was associated with a higher antibody titer. After adjustment for age, smoking, family history of AMD, history of cardiovascular diseases, and source study, the subjects in the upper tertiles of antibody titers were 2.1 (95% confidence interval: 0.92, 4.69), 2.6 (95% confidence interval: 1.24, 5.41), and 3.0 (95% confidence interval: 1.46, 6.37) times more at risk of progression than those in the lowest tertile, using three definitions of progression, respectively. The fact that seroreactivity to C. pneumoniae was independently associated with the risk of AMD progression suggests that C. pneumoniae infection may be an additional risk factor for AMD progression.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    USDA-ARS?s Scientific Manuscript database

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

    ERIC Educational Resources Information Center

    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…

  17. Traditional Chinese Medicine (TCM) for the treatment of Age-related Macular Degeneration--Evaluation of WO2012079419

    PubMed Central

    Cunnusamy, Khrishen

    2013-01-01

    A pharmaceutical composition composed of several traditional Chinese medicines is claimed to treat Age-related Macular Degeneration (AMD). This represents a novel and alternative therapeutic solution for wet AMD, with the potential advantage of treating both the symptoms and the underlying causes of this devastating degenerative retinal disease. PMID:23215532

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

    ERIC Educational Resources Information Center

    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…

  19. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    USDA-ARS?s Scientific Manuscript database

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  20. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    PubMed Central

    Fong, Angie HC; Lai, Timothy YY

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

  1. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema.

    PubMed

    Fong, Angie H C; Lai, Timothy Y Y

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed.

  2. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD.

    PubMed

    Datta, Sayantan; Cano, Marisol; Ebrahimi, Katayoon; Wang, Lei; Handa, James T

    2017-09-01

    The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch's membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies. Oxidative stress and inflammation have both physiological and potentially pathological roles in RPE degeneration. Given the central role of the RPE, this review will focus on the impact of oxidative stress and inflammation on the RPE with AMD pathobiology. Physiological sources of oxidative stress as well as unique sources from photo-oxidative stress, the phagocytosis of photoreceptor outer segments, and modifiable factors such as cigarette smoking and high fat diet ingestion that can convert oxidative stress into a pathological role, and the negative impact of impairing the cytoprotective roles of mitochondrial dynamics and the Nrf2 signaling system on RPE health in AMD will be discussed. Likewise, the response by the innate immune system to an inciting trigger, and the potential role of local RPE production of inflammation, as well as a potential role for damage by inflammation with chronicity if the inciting trigger is not neutralized, will be debated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Nanoceria: a Potential Therapeutic for Dry AMD.

    PubMed

    Cai, Xue; McGinnis, James F

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of blinding diseases. The "dry" form of AMD is the most common form of AMD. In contrast to the treatable neovascular (wet) AMD, no effective treatment is available for dry AMD. In this review, we summarize the animal models and therapeutic strategies for dry AMD. The novel candidates as potential treatment targets and the potential effectiveness of nanoceria as a treatment of dry AMD are also discussed.

  4. Imaging Polarimetry in Age-Related Macular Degeneration

    PubMed Central

    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

  5. Seven New Loci Associated with Age-Related Macular Degeneration

    PubMed Central

    2013-01-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

  6. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  7. Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

    PubMed

    Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

    2014-09-01

    To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Meta-analysis. setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD. The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. New approaches and potential treatments for dry age-related macular degeneration.

    PubMed

    Damico, Francisco Max; Gasparin, Fabio; Scolari, Mariana Ramos; Pedral, Lycia Sampaio; Takahashi, Beatriz Sayuri

    2012-01-01

    Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  9. The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

    2008-01-01

    Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

  10. Suspected macular degeneration in a captive Western lowland gorilla (Gorilla gorilla gorilla).

    PubMed

    Steinmetz, Andrea; Bernhard, Andreas; Sahr, Sabine; Oechtering, Gerhard

    2012-09-01

    The case of a 31-year-old captive female Western lowland gorilla (Gorilla gorilla gorilla) with decreased near vision but good distance vision is presented. Examination of the fundus revealed drusen-like bodies in the macula presumably because of an age-related macular degeneration (AMD). © 2012 American College of Veterinary Ophthalmologists.

  11. The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

    2008-01-01

    Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration

    PubMed Central

    Herzlich, Alexandra A.; Tuo, Jingsheng; Chan, Chi-Chao

    2008-01-01

    Age-related macular degeneration (AMD) is the leading cause of new blindness in the western world and is becoming more of a socio-medical problem as the proportion of the aged population increases. There are multiple efforts underway to better understand this disease process. AMD involves the abnormal retinal pigment epithelium (RPE), drusen formation, photoreceptor atrophy, and choroidal neovascularization. Peroxisome proliferator-activated receptors (PPARs) play an important role in lipid degeneration, immune regulation, regulation of reactive oxygen species (ROSs), as well as regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and docosahexaenoic acid (DHA). These molecules have all been implicated in the pathogenesis of AMD. In addition, PPAR gamma is expressed in RPE, an essential cell in photoreceptor regeneration and vision maintenance. This review summarizes the interactions between PPAR, AMD-related molecules, and AMD-related disease processes. PMID:18288287

  15. Estrogen signalling in the pathogenesis of age-related macular degeneration.

    PubMed

    Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

    2015-02-01

    Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

  16. Divergence in the lived experience of people with macular degeneration.

    PubMed

    McCloud, Christine; Khadka, Jyoti; Gilhotra, Jagjit Singh; Pesudovs, Konrad

    2014-08-01

    The aim of this study was to understand people's experience with age-related macular degeneration (AMD) in light of new treatment successes. An interpretive qualitative methodology was used to facilitate understanding of the experience of people with AMD. Rich in-depth data were collected using focus groups and individual interviews. Thematic analysis of the data occurred through the processes of line-by-line coding, aggregation, and theme development using the NVivo 10 software. A total of 4 focus groups and 16 individual interviews were conducted with 34 people (median age = 81 years; range = 56 to 102 years; 19 females) with AMD. Four major themes arose from the narratives of the participants: cautious optimism, enduring, adaptation, and profound loss. Cautious optimism resonated for participants who had received successful treatment and stabilization of AMD. Enduring emerged as participants with exudative AMD described an ongoing need for invasive and frequent treatments (anti-vascular endothelial growth factor injections) that maintained their vision. Adaptation was evident in the narratives of all participants and was directly related to the physical and psychological limitations that were a consequence of visual disability. Profound loss encompassed both physical and emotional aspects of deteriorating vision and was most evident in patients for whom treatment had failed or had not been considered appropriate for their disease. The findings of this study shed new light on the influence of underlying pathology, disease trajectory, and success of new treatments on quality of life of people living with AMD. Optimism toward maintaining vision in the presence of exudative AMD was described by participants, moderated by ongoing caution and a need for endurance of frequent and often problematic intravitreal treatments. These findings add a deeper understanding of this complex and life-changing experience.

  17. Combined treatment modalities for age related macular degeneration.

    PubMed

    Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

    2011-02-01

    Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of

  18. Postreceptor Neuronal Loss in Intermediate Age-related Macular Degeneration.

    PubMed

    Borrelli, Enrico; Abdelfattah, Nizar Saleh; Uji, Akihito; Nittala, Muneeswar Gupta; Boyer, David S; Sadda, SriniVas R

    2017-09-01

    To investigate the relationship between ganglion cell complex (GCC) thickness and photoreceptor alterations in eyes with intermediate age-related macular degeneration (AMD). Retrospective case-control study. We collected data from 68 eyes with intermediate AMD from 68 patients with spectral-domain optical coherence tomography (SDOCT) imaging. A control group of 50 eyes from 50 healthy subjects was included for comparison. Our main outcome measures for comparison between groups were (1) the average and minimum GCC thickness and (2) the "normalized" reflectivity of the ellipsoid zone (EZ) en face image. The average and minimum GCC thicknesses were thinner in AMD patients (69.54 ± 9.30 μm and 63.22 ± 14.11 μm, respectively) than in healthy controls (78.57 ± 6.28 μm and 76.28 ± 6.85 μm, P < .0001 and P < .0001, respectively). Agreement was found to be excellent in the "normalized" EZ reflectivity assessment (intraclass correlation coefficient = 0.986, coefficient of variation = 1.11). The EZ "normalized" reflectivity was 0.67 ± 0.11 in controls and 0.61 ± 0.09 in the AMD group (P = .006). In univariate analysis, EZ "normalized" reflectivity was found to have a significant direct relationship with average (P < .0001) and minimum (P < .0001) GCC thickness in AMD patients, but not in controls (P = .852 and P = .892, respectively). Eyes with intermediate AMD exhibit GCC thinning, as well as a reduced EZ "normalized" reflectivity, and these parameters are correlated. This study supports the concept of postreceptor retinal neuronal loss as a contributor to retinal thinning in intermediate AMD. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration

    PubMed Central

    Swaroop, Anand; Chew, Emily Y.; Rickman, Catherine Bowes; Abecasis, Gonçalo R.

    2012-01-01

    Aging-associated neurodegenerative diseases significantly influence the quality of life of affected individuals. Genetic approaches, combined with genomic technology, have provided powerful insights into common late-onset diseases, such as age-related macular degeneration (AMD). Here, we discuss current findings on the genetics of AMD to highlight areas of rapid progress and new challenges. We also attempt to integrate available genetic and biochemical data with cellular pathways involved in aging to formulate an integrated model of AMD pathogenesis. PMID:19405847

  20. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    PubMed

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    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 (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  1. Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration.

    PubMed

    Cheung, Chui Ming Gemmy; Gan, Alfred; Fan, Qiao; Chee, Miao Ling; Apte, Rajendra S; Khor, Chiea Chuen; Yeo, Ian; Mathur, Ranjana; Cheng, Ching-Yu; Wong, Tien Yin; Tai, E Shyong

    2017-09-01

    Disturbance in lipid metabolism has been suggested as a major pathogenic factor for age-related macular degeneration (AMD). Conventional lipid measures have been inconsistently associated with AMD. Other factors that can alter lipid metabolism include lipoprotein phenotype and genetic mutations. We performed a case-control study to examine the association between lipoprotein profile and neovascular AMD (nAMD) and whether the cholesterylester transfer protein (CETP) D442G mutation modulates these associations. Patients with nAMD had significantly higher concentrations of HDL and IDL compared with controls. The increase in HDL particles in nAMD patients was driven by an excess of medium-sized particles. Concurrently, patients with nAMD also had lower Apo A-1, lower VLDL and chylomicron lipoprotein. Many of these associations showed a dose-dependent association between controls, early AMD cases, and nAMD cases. Adjustment for the presence of the D442G mutation at the CETP locus did not significantly alter the increased AMD risk associated with HDL particle concentration. AMD is associated with variation in many lipoprotein subclasses, including increased HDL and IDL particles and decreased Apo A-1, VLDL, and chylomicron particles. These data suggest widespread systemic disturbance in lipid metabolism in the pathogenesis of AMD, including possible alterations in lipoprotein carrier capacity. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  2. Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

    PubMed Central

    Grassmann, Felix; Heid, Iris M.; Weber, Bernhard H. F.

    2017-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 1.0 × 10−773 and 6.7 × 10−5. This now allows prioritization of the gene of interest for subsequent functional studies. PMID:27879347

  3. The NLRP3 Inflammasome and its Role in Age-Related Macular Degeneration.

    PubMed

    Ildefonso, Cristhian J; Biswal, Manas R; Ahmed, Chulbul M; Lewin, Alfred S

    2016-01-01

    Age related macular degeneration (AMD) is the most common cause of blindness among people of 65 years and older in developed countries (Klein and Klein, Invest Ophthalmol Vis Sci 54:7395-7401, 2013). Recent advances in dry AMD research points towards an important role of the inflammatory response in the development of the disease. The presence of inflammatory cells, antibodies, complement factors and pro-inflammatory cytokines in AMD retinas and drusen indicates that the immune system could be an important driving force in dry AMD. The NLRP3 inflammasome has been proposed as an integrator of process associated with AMD and the induction of inflammation. Herein we summarize the most recent studies that attempt to understand the role of the NLRP3 inflammasome in AMD.

  4. Visual-function tests for self-monitoring of age-related macular degeneration.

    PubMed

    Liu, Lei; Wang, Yi-Zhong; Bedell, Harold E

    2014-08-01

    Age-related macular degeneration (AMD) is one of the leading causes of severe visual impairment in the United States. Changes in lifestyle can slow the progression of AMD, and new therapies that arrest choroidal neovascularization can preserve vision in patients who progress to the neovascular form of advanced AMD. Appropriate timing is required for these interventions to be optimally effective, which, in turn, depends critically on early diagnosis. Because annual or semiannual eye examinations may not be sufficient to ensure an early diagnosis, the preferred practice for AMD management must include self-monitoring by patients for disease onset or progression. In this review, we discuss a number of visual functions that have been shown to be impaired in eyes with AMD and specify desirable characteristics of visual-function tests that can be used for self-monitoring by populations at risk for AMD.

  5. Loss of endothelial planar cell polarity and cellular clearance mechanisms in age-related macular degeneration.

    PubMed

    Campos, Maria Mercedes; Abu-Asab, Mones S

    2017-01-01

    Apoptosis, autophagosomes, and lysosomes are lacking in the retinal pigment epithelium (RPE) of age-related macular degeneration (AMD) eyes. Necrosis, not apoptosis, appeared to be the prominent type of cell death in RPE, which led to the accumulation of cell debris within and on both sides of Bruch's membrane. The endothelium of the choriocapillaris had an altered planar cell polarity which encompassed the disappearance of fenestrations, the thickening of cytoplasm, and anterior nuclear dislocation. There were no significant differences in RPE and choroidal aberrations between macular and temporal regions. Loss of endothelial polarity could be at the crux of AMD initiation and progression.

  6. Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.

    PubMed

    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.

  7. Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration.

    PubMed

    Katz, Martin L

    2002-01-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment in developed countries. The vision loss associated with AMD is the result of degenerative changes in the central region of the retina called the macula. Maintenance of normal structure and function of the macular retina, and of the remainder of the retina as well, is critically dependent on the supporting role of the adjacent retinal pigment epithelium (RPE). Impairment of normal RPE functions is known to result in retinal degeneration and loss of visual function. Thus, it has been hypothesized that the retinal degeneration that characterizes AMD is secondary to age-related deterioration in RPE support functions. Like many other postmitotic cell types, the RPE accumulates autofluorescent lysosomal storage bodies (lipofuscin) during senescence. In human eyes, lipofuscin comes to occupy a substantial fraction of the RPE cytoplasmic volume in the elderly. Does this lipofuscin accumulation contribute to the development of AMD? This question is a specific case of the broader question of whether lipofuscin accumulation in general is detrimental to cells. Unfortunately, definitive data do not exist to allow these questions to be answered. Although a correlation between RPE lipofuscin content and AMD has been reported, a cause-and-effect relationship between RPE lipofuscin accumulation and the development of this disease has not been established. It has been reported that a mutation in a gene encoding a photoreceptor-specific protein results in massive RPE lipofuscin accumulation and early-onset macular degeneration. However, again the accelerated RPE lipofuscin accumulation has not been shown to be the cause of the accompanying macular degeneration. The lack of a definitive link between RPE lipofuscin accumulation and AMD illustrates one of the biggest challenges remaining in lipofuscin research-determining whether lipofuscin accumulation per se has an impact on cell function.

  8. Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis.

    PubMed

    Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan

    2016-06-01

    Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Prevalence of age-related macular degeneration in rural southern China: the Yangxi Eye Study.

    PubMed

    Jin, Guangming; Ding, Xiaohu; Xiao, Wei; Xu, Xiao; Wang, Lanhua; Han, Xiaotong; Xiao, Ou; Liu, Ran; Wang, Wei; Yan, William; An, Lei; Zhao, Jialiang; He, Mingguang

    2017-08-28

    To describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China. Eligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations. Of 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%). AMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive, late-onset disorder of the macula affecting central vision. It is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown that AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2016), EMBASE (January 1980 to March 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2016), PubMed (January 1946 to March 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 5 June 2014), 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 31 March 2016. Selection criteria We included randomized controlled trials (RCTs) and quasi-randomized trials that compared statins with other treatments, no treatment, or placebo in people who were diagnosed as having the early stages of AMD. Data collection and analysis We used standard methodological procedures expected by Cochrane. Two review authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to

  11. Do nutritional supplements have a role in age macular degeneration prevention?

    PubMed

    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.

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

    PubMed Central

    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

  13. Seven new loci associated with age-related macular degeneration.

    PubMed

    Fritsche, Lars G; Chen, Wei; Schu, Matthew; Yaspan, Brian L; Yu, Yi; Thorleifsson, Gudmar; Zack, Donald J; Arakawa, Satoshi; Cipriani, Valentina; Ripke, Stephan; Igo, Robert P; Buitendijk, Gabriëlle H S; Sim, Xueling; Weeks, Daniel E; Guymer, Robyn H; Merriam, Joanna E; Francis, Peter J; Hannum, Gregory; Agarwal, Anita; Armbrecht, Ana Maria; Audo, Isabelle; Aung, Tin; Barile, Gaetano R; Benchaboune, Mustapha; Bird, Alan C; Bishop, Paul N; Branham, Kari E; Brooks, Matthew; Brucker, Alexander J; Cade, William H; Cain, Melinda S; Campochiaro, Peter A; Chan, Chi-Chao; Cheng, Ching-Yu; Chew, Emily Y; Chin, Kimberly A; Chowers, Itay; Clayton, David G; Cojocaru, Radu; Conley, Yvette P; Cornes, Belinda K; Daly, Mark J; Dhillon, Baljean; Edwards, Albert O; Evangelou, Evangelos; Fagerness, Jesen; Ferreyra, Henry A; Friedman, James S; Geirsdottir, Asbjorg; George, Ronnie J; Gieger, Christian; Gupta, Neel; Hagstrom, Stephanie A; Harding, Simon P; Haritoglou, Christos; Heckenlively, John R; Holz, Frank G; Hughes, Guy; Ioannidis, John P A; Ishibashi, Tatsuro; Joseph, Peronne; Jun, Gyungah; Kamatani, Yoichiro; Katsanis, Nicholas; N Keilhauer, Claudia; Khan, Jane C; Kim, Ivana K; Kiyohara, Yutaka; Klein, Barbara E K; Klein, Ronald; Kovach, Jaclyn L; Kozak, Igor; Lee, Clara J; Lee, Kristine E; Lichtner, Peter; Lotery, Andrew J; Meitinger, Thomas; Mitchell, Paul; Mohand-Saïd, Saddek; Moore, Anthony T; Morgan, Denise J; Morrison, Margaux A; Myers, Chelsea E; Naj, Adam C; Nakamura, Yusuke; Okada, Yukinori; Orlin, Anton; Ortube, M Carolina; Othman, Mohammad I; Pappas, Chris; Park, Kyu Hyung; Pauer, Gayle J T; Peachey, Neal S; Poch, Olivier; Priya, Rinki Ratna; Reynolds, Robyn; Richardson, Andrea J; Ripp, Raymond; Rudolph, Guenther; Ryu, Euijung; Sahel, José-Alain; Schaumberg, Debra A; Scholl, Hendrik P N; Schwartz, Stephen G; Scott, William K; Shahid, Humma; Sigurdsson, Haraldur; Silvestri, Giuliana; Sivakumaran, Theru A; Smith, R Theodore; Sobrin, Lucia; Souied, Eric H; Stambolian, Dwight E; Stefansson, Hreinn; Sturgill-Short, Gwen M; Takahashi, Atsushi; Tosakulwong, Nirubol; Truitt, Barbara J; Tsironi, Evangelia E; Uitterlinden, André G; van Duijn, Cornelia M; Vijaya, Lingam; Vingerling, Johannes R; Vithana, Eranga N; Webster, Andrew R; Wichmann, H-Erich; Winkler, Thomas W; Wong, Tien Y; Wright, Alan F; Zelenika, Diana; Zhang, Ming; Zhao, Ling; Zhang, Kang; Klein, Michael L; Hageman, Gregory S; Lathrop, G Mark; Stefansson, Kari; Allikmets, Rando; Baird, Paul N; Gorin, Michael B; Wang, Jie Jin; Klaver, Caroline C W; Seddon, Johanna M; Pericak-Vance, Margaret A; Iyengar, Sudha K; Yates, John R W; Swaroop, Anand; Weber, Bernhard H F; Kubo, Michiaki; Deangelis, Margaret M; Léveillard, Thierry; Thorsteinsdottir, Unnur; Haines, Jonathan L; Farrer, Lindsay A; Heid, Iris M; Abecasis, Gonçalo R

    2013-04-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

  14. Object crowding in age-related macular degeneration

    PubMed Central

    Wallace, Julian M.; Chung, Susana T. L.; Tjan, Bosco S.

    2017-01-01

    Crowding, the phenomenon of impeded object identification due to clutter, is believed to be a key limiting factor of form vision in the peripheral visual field. The present study provides a characterization of object crowding in age-related macular degeneration (AMD) measured at the participants' respective preferred retinal loci with binocular viewing. Crowding was also measured in young and age-matched controls at the same retinal locations, using a fixation-contingent display paradigm to allow unlimited stimulus duration. With objects, the critical spacing of crowding for AMD participants was not substantially different from controls. However, baseline contrast energy thresholds in the noncrowded condition were four times that of the controls. Crowding further exacerbated deficits in contrast sensitivity to three times the normal crowding-induced contrast energy threshold elevation. These findings indicate that contrast-sensitivity deficit is a major limiting factor of object recognition for individuals with AMD, in addition to crowding. Focusing on this more tractable deficit of AMD may lead to more effective remediation and technological assistance. PMID:28129416

  15. Gene transfer for neovascular age-related macular degeneration.

    PubMed

    Campochiaro, Peter A

    2011-05-01

    Age-related macular degeneration (AMD) is a complex disease that has two phases: a degenerative phase often referred to as nonneovascular AMD (non-NVAMD) or dry AMD and a phase dominated by growth of new blood vessels in the subretinal space, referred to as NVAMD or wet AMD. Advances in the understanding of the molecular pathogenesis of NVAMD have led to new drug therapies that have provided major benefits to patients. However, those treatments require frequent intraocular injections that in many patients must be continued indefinitely to maintain visual benefits. Gene transfer to augment expression of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term stability in patients with NVAMD. Studies in animal models that mimic aspects of NVAMD have identified several possible transgenes, and a clinical trial in patients with advanced NVAMD has suggested that the approach may be feasible. Many important questions remain, but the rationale and preliminary data are compelling. The results of two ongoing clinical trials may answer several of the questions and help direct future research.

  16. Activity loss and depression in age-related macular degeneration.

    PubMed

    Rovner, Barry W; Casten, Robin J

    2002-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of severe vision loss in older persons and is associated with high rates of disability and depression. The authors evaluated 51 patients with bilateral AMD to investigate the interrelationships of disease severity, disability, and depression and focused on loss of valued activities as an emblematic disabling consequence of AMD. They characterized depression by the Center for Epidemiologic Studies-Depression (CES-D) score, a syndromal state based on the CES-D, and as a level of distress (Index of Affective Suffering; IAS). Thirty subjects (58.8%) had loss of a valued, discretionary activity. They had worse visual acuity and more depressive symptoms and were represented in higher IAS levels than other subjects. Visual acuity was significantly correlated with IAS levels, but not with CES-D scores or syndromal depression. A regression model demonstrated that activity loss mediated the relationship between visual acuity and IAS level. Affective distress occurs in AMD, largely to the extent that valued activities are relinquished because of vision loss. IAS levels best illuminated this relationship, suggesting the value of this dimension of affective functioning in studies of the consequences of chronic disease.

  17. Treatment of age-related macular degeneration: focus on ranibizumab

    PubMed Central

    Spitzer, Martin S; Ziemssen, Focke; Bartz-Schmidt, Karl U; Gelisken, Faik; Szurman, Peter

    2008-01-01

    Ranibizumab, a humanized antigen-binding fragment (Fab) that binds all isoforms of VEGF-A, significantly slows down loss of vision and causes significant visual improvement in many patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD). These benefits of intravitreal ranibizumab apply to all angiographic subtypes of neovascular AMD and across all lesion sizes when the drug is injected at monthly intervals as shown in two pivotal phase III trials (ANCHOR and MARINA). The results from the PrONTO study suggest that less frequent treatment with ranibizumab through a variable dosing regimen dependent on optical coherence tomography (OCT) findings is a treatment option that results in comparably favorable visual outcomes. Currently, it is unclear whether combination therapy of ranibizumab with photodynamic therapy (PDT) provides any significant advantage over ranibizumab monotherapy (FOCUS trial); however, the combination of PDT and ranibizumab may decrease the need for frequent retreatment. This question will be addressed in the SUMMIT trial. Therapy with ranibizumab is generally very well tolerated with a low rate of seriously adverse ocular events or systemic side-effects. The advent of vascular endothelial growth factor (VEGF) inhibitors has revolutionized the therapy of neovascular AMD. Ranibizumab at the moment appears to be the most effective approved treatment for neovascular AMD. PMID:19668384

  18. Fear of falling in age-related macular degeneration.

    PubMed

    van Landingham, Suzanne W; Massof, Robert W; Chan, Emilie; Friedman, David S; Ramulu, Pradeep Y

    2014-01-28

    Prior studies have shown age-related macular degeneration (AMD) to be associated with falls. The purpose of this study is to determine if (AMD) and AMD-related vision loss are associated with fear of falling, an important and distinct outcome. Sixty-five persons with AMD with evidence of vision loss in one or both eyes and 60 glaucoma suspects with normal vision completed the University of Illinois at Chicago Fear of Falling questionnaire. Responses were Rasch analyzed. Scores were expressed in logit units, with lower scores demonstrating lesser ability and greater fear of falling. Compared to glaucoma suspect controls, AMD subjects had worse visual acuity (VA) (median better-eye VA = 20/48 vs. 20/24, p < 0.001) and worse contrast sensitivity (CS) (binocular CS = 1.9 vs. 1.5 log units, p < 0.001). AMD subjects were also older, more likely to be Caucasian, and less likely to be employed (p < 0.05 for all), but were similar with regards to other demographic and health measures. In multivariable models controlling for age, gender, body habitus, strength, and comorbid illnesses, AMD subjects reported greater fear of falling as compared to controls (β = -0.77 logits, 95% CI = -1.5 to -0.002, p = 0.045). In separate multivariable models, fear of falling increased with worse VA (β = -0.15 logits/1 line decrement, 95% CI = -0.28 to -0.03, p = 0.02) and CS (β = -0.20 logits/0.1 log unit decrement, 95% CI = -0.31 to -0.09, p = 0.001). Greater fear of falling was also associated with higher BMI, weaker grip, and more comorbid illnesses (p < 0.05 for all). AMD and AMD-related vision loss are associated with greater fear of falling in the elderly. Development, validation, and implementation of methods to address falls and fear of falling for individuals with vision loss from AMD are important goals for future work.

  19. Fear of falling in age-related macular degeneration

    PubMed Central

    2014-01-01

    Background Prior studies have shown age-related macular degeneration (AMD) to be associated with falls. The purpose of this study is to determine if (AMD) and AMD-related vision loss are associated with fear of falling, an important and distinct outcome. Methods Sixty-five persons with AMD with evidence of vision loss in one or both eyes and 60 glaucoma suspects with normal vision completed the University of Illinois at Chicago Fear of Falling questionnaire. Responses were Rasch analyzed. Scores were expressed in logit units, with lower scores demonstrating lesser ability and greater fear of falling. Results Compared to glaucoma suspect controls, AMD subjects had worse visual acuity (VA) (median better-eye VA = 20/48 vs. 20/24, p < 0.001) and worse contrast sensitivity (CS) (binocular CS = 1.9 vs. 1.5 log units, p < 0.001). AMD subjects were also older, more likely to be Caucasian, and less likely to be employed (p < 0.05 for all), but were similar with regards to other demographic and health measures. In multivariable models controlling for age, gender, body habitus, strength, and comorbid illnesses, AMD subjects reported greater fear of falling as compared to controls (β = -0.77 logits, 95% CI = -1.5 to -0.002, p = 0.045). In separate multivariable models, fear of falling increased with worse VA (β = -0.15 logits/1 line decrement, 95% CI = -0.28 to -0.03, p = 0.02) and CS (β = -0.20 logits/0.1 log unit decrement, 95% CI = -0.31 to -0.09, p = 0.001). Greater fear of falling was also associated with higher BMI, weaker grip, and more comorbid illnesses (p < 0.05 for all). Conclusions AMD and AMD-related vision loss are associated with greater fear of falling in the elderly. Development, validation, and implementation of methods to address falls and fear of falling for individuals with vision loss from AMD are important goals for future work. PMID:24472499

  20. Binocular contrast inhibition in subjects with age-related macular degeneration.

    PubMed

    Valberg, Arne; Fosse, Per

    2002-01-01

    In subjects with normal vision, binocular contrast sensitivity is generally higher than monocular sensitivity, indicating summation of contrast in the two eyes. We have compared monocular and binocular contrast sensitivity and acuity for a group of 13 subjects with age-related macular degeneration (AMD). Relative to a normal control group, many of the AMD subjects showed reduced binocular contrast summation, and binocular inhibition was found for eight subjects for a narrow or an extended frequency band. A better monocular than binocular function may have practical implications for reading and orientation in AMD.

  1. What can we learn about age-related macular degeneration from other retinal diseases?

    PubMed

    Zack, D J; Dean, M; Molday, R S; Nathans, J; Redmond, T M; Stone, E M; Swaroop, A; Valle, D; Weber, B H

    1999-11-03

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  2. [New aspects in age related macular degeneration].

    PubMed

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  3. Inferring diagnosis and trajectory of wet age-related macular degeneration from OCT imagery of retina

    NASA Astrophysics Data System (ADS)

    Irvine, John M.; Ghadar, Nastaran; Duncan, Steve; Floyd, David; O'Dowd, David; Lin, Kristie; Chang, Tom

    2017-03-01

    Quantitative biomarkers for assessing the presence, severity, and progression of age-related macular degeneration (AMD) would benefit research, diagnosis, and treatment. This paper explores development of quantitative biomarkers derived from OCT imagery of the retina. OCT images for approximately 75 patients with Wet AMD, Dry AMD, and no AMD (healthy eyes) were analyzed to identify image features indicative of the patients' conditions. OCT image features provide a statistical characterization of the retina. Healthy eyes exhibit a layered structure, whereas chaotic patterns indicate the deterioration associated with AMD. Our approach uses wavelet and Frangi filtering, combined with statistical features that do not rely on image segmentation, to assess patient conditions. Classification analysis indicates clear separability of Wet AMD from other conditions, including Dry AMD and healthy retinas. The probability of correct classification of was 95.7%, as determined from cross validation. Similar classification analysis predicts the response of Wet AMD patients to treatment, as measured by the Best Corrected Visual Acuity (BCVA). A statistical model predicts BCVA from the imagery features with R2 = 0.846. Initial analysis of OCT imagery indicates that imagery-derived features can provide useful biomarkers for characterization and quantification of AMD: Accurate assessment of Wet AMD compared to other conditions; image-based prediction of outcome for Wet AMD treatment; and features derived from the OCT imagery accurately predict BCVA; unlike many methods in the literature, our techniques do not rely on segmentation of the OCT image. Next steps include larger scale testing and validation.

  4. Bevasiranib for the treatment of wet, age-related macular degeneration.

    PubMed

    Garba, Adinoyi O; Mousa, Shaker A

    2010-01-01

    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. MACULAR DEGENERATION AND ASPIRIN USE.

    PubMed

    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.

  6. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

    PubMed

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

    2017-02-01

    To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration

    PubMed Central

    Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). Methods 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Results Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). Conclusions MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. Trial registration number ISRCTN13894787. PMID:27091854

  8. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    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.

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

    PubMed Central

    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

  10. Age-Related Macular Degeneration and Incident Stroke: A Systematic Review and Meta-Analysis

    PubMed Central

    Fernandez, Antonio B.; Panza, Gregory A.; Cramer, Benjamin; Chatterjee, Saurav; Jayaraman, Ramya; Wu, Wen-Chih

    2015-01-01

    Background Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over 65 years old in the United States and has been associated with cardiovascular risk and decreased survival. There is conflicting data, however, regarding the contribution of AMD to the prediction of stroke. Aim To determine whether AMD is a risk indicator for incident stroke in a meta-analysis of available prospective and retrospective cohort studies published in the English literature. Methods We performed a systematic literature search of all studies published in English with Pub Med and other databases from 1966 to August 2014, reporting stroke incidence in patients with macular degeneration. Two investigators independently extracted the data. A random effects model was used to report Odds ratios (OR), with corresponding 95% confidence intervals (CI). Meta-regression using a mixed linear model was used to understand potential heterogeneity amongst studies. Results We identified 9 studies that reported stroke incidence in patients with and without early AMD (N = 1,420,978). No significant association was found between early AMD with incident stroke. Combined, these 9 studies demonstrated random effects (OR, 1.12; CI, 0.86–1.47; I2 = 96%). Meta-regression on baseline covariates of age, sex, and year of publication did not significantly relate to heterogeneity. Conclusions We found no significant relationship between AMD and incident stroke. Further studies are needed to clarify other causes of decreased survival in patients with AMD. PMID:26580396

  11. Lifestyle modification, nutritional and vitamins supplements for age-related macular degeneration.

    PubMed

    Sin, Helena P Y; Liu, David T L; Lam, Dennis S C

    2013-02-01

    To provide a systematic review of the published studies pertaining to the lifestyle modification, dietary, nutritional and vitamins supplements for preventing occurrence or halting deterioration of age-related macular degeneration (AMD). The literature searches from 1990 to December 2010 with following keywords, 'age related macular degeneration', 'nutrition', 'antioxidant', 'diet' and 'vitamins supplements' using search engines Pubmed, Google Scholar, Medline and the Cochrane Library. Meta-analyses, population-based cohort studies and case-controlled trials were reviewed, whereas small cases series, case reports, commentaries, abstracts in proceedings or personal observations were excluded. Smoking and obesity are identified risk factors for AMD. High dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalence and incidence in AMD. Vitamin B and extracts from wolfberry, Gingko biloba and berry anthocyanins were also subjects of intense research interests, but there has been no concluding scientific evidence yet. The Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show beneficial effect of AREDS formulation of vitamins C, E, beta-carotene and zinc with copper in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye. Quit smoking is an important advice to patients to prevent or slow the progress of AMD. There is no recommendation for routine nutritional or vitamins supplementation for primary prevention. However, patients with documented intermediate risk of AMD or advanced AMD in one eye are recommended to take AREDS-type vitamin supplements. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

  12. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  13. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  14. MACULAR ATROPHY AND MACULAR MORPHOLOGY IN AFLIBERCEPT-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Kuroda, Yoshimasa; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Oishi, Akio; Nakanishi, Hideo; Miyata, Manabu; Hata, Masayuki; Takahashi, Ayako; Wakazono, Tomotaka; Yoshimura, Nagahisa; Tsujikawa, Akitaka

    2017-07-04

    To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients. This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy. This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment. Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.

  15. Genetic studies of Age-related macular degeneration: lessons, challenges and opportunities for disease management

    PubMed Central

    Ratna Priya, Rinki; Chew, Emily Y.; Swaroop, Anand

    2012-01-01

    Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals over 55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic and non-genetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from human genome project, genomewide association studies and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Here, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher a new era of personalized medicine in the clinical management of AMD. PMID:23009893

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

    PubMed Central

    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

  17. Emerging roles for nuclear receptors in the pathogenesis of age-related macular degeneration

    PubMed Central

    Malek, Goldis; Lad, Eleonora M.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly in the Western world. Over the last 30 years, our understanding of the pathogenesis of the disease has grown exponentially thanks to the results of countless epidemiology, genetic, histo-logical, and biochemical studies. This information, in turn, has led to the identification of multiple biologic pathways potentially involved in development and progression of AMD, including but not limited to inflammation, lipid and extracellular matrix dysregulation, and angiogenesis. Nuclear receptors are a superfamily of transcription factors that have been shown to regulate many of the pathogenic pathways linked with AMD and as such they are emerging as promising targets for therapeutic intervention. In this review, we will present the fundamental phenotypic features of AMD and discuss our current understanding of the pathobiological disease mechanisms. We will introduce the nuclear receptor superfamily and discuss the current literature on their effects on AMD-related pathophysiology. PMID:25156067

  18. The role of molecular genetic factors in age-related macular degeneration.

    PubMed

    Almeida, Luciana Negrão Frota de; Carolino, Rachel Melilo; Sperandio, Diogo Cazelli; Nehemy, Márcio Bittar; De Marco, L A

    2009-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Although the etiology of AMD remains largely unknown, numerous studies have suggested that both genes and environmental risk factors significantly influence the risk of developing AMD. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement factor H (CFH) gene, have been found to be strongly associated with the development of AMD. Several other genes have had at least one positive association finding and deserve further exploration. The purpose of this review is to provide an extensive report of the current data of AMD genetics and the contribution of this knowledge helps to the better understanding of its pathophysiology.

  19. Age-related macular degeneration-clinical review and genetics update.

    PubMed

    Ratnapriya, R; Chew, E Y

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients.

  20. Age-related macular degeneration: genetic and environmental factors of disease.

    PubMed

    Chen, Yuhong; Bedell, Matthew; Zhang, Kang

    2010-10-01

    Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as the population ages; however, treatment options remain limited because the etiology and pathogenesis of AMD are incompletely defined. Recently, much progress has been made in gene discovery and mechanistic studies, which clearly indicate that AMD involves the interaction of multiple genetic and environmental factors. The identification of genes that have a substantial impact on the risk for AMD is not only facilitating the diagnosis and screening of populations at risk but is also elucidating key molecular pathways of pathogenesis. Pharmacogenetic studies of treatment responsiveness among patients with the "wet" form of AMD are increasingly proving to be clinically relevant; pharmacogenetic approaches hold great promise for both identifying patients with the best chance for vision recovery as well as tailoring individualized therapies.

  1. Efficacy of vitrectomy and epiretinal membrane peeling in eyes with dry age-related macular degeneration.

    PubMed

    Mason, John O; Patel, Shyam A

    2015-01-01

    To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry age-related macular degeneration (AMD). We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD. Eyes with concurrent dry AMD and with a good preoperative best-corrected visual acuity (BCVA) (better than or equal to 20/50) had a statistically significant mean BCVA improvement at 6 months after ERM peeling. There was a statistical increase in mean BCVA from 20/95 to 20/56 in dry AMD eyes, and no eyes showed worsening in BCVA at 6 months or at most recent follow-up. Five/seventeen (29.4%) eyes had cataract formation or progression. There were no other complications, reoperations, or reoccurrences. ERM peeling in eyes with dry AMD may show significant improvement, especially in eyes with good preoperative BCVA. The procedure is relatively safe with low complications and reoccurrences.

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

    PubMed Central

    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

  3. The vitreomacular interface in different types of age-related macular degeneration

    PubMed Central

    El-Hifnawy, Mohamed Abd ElMonaem; Ibrahim, Hisham Ali; Gomaa, Amir Ramadan; Elmasry, Mohamed A

    2017-01-01

    AIM To evaluate the vitreomacular interface in cases with wet age-related macular degeneration (AMD) and to compare them to eyes with dry AMD and normal eyes. METHODS This was a cross-sectional comparative study that included 87 eyes with wet AMD, 42 eyes with dry AMD and 40 eyes without AMD as a control group. Optical coherence tomography (OCT) examination was performed for all patients to assess the vitreomacular interface. RESULTS In the wet AMD group, 34.5% of cases had vitreomacular adhesion (VMA). Only 14.3% of dry AMD cases and 10% of control cases had VMA. There was a significant difference between the control group and the wet AMD group (P=0.004) as well as the dry and wet AMD group (P=0.017). There was also a significant difference between the incidence of VMA in patients with subretinal choroidal neovascularization (CNV, type 1) and intraretinal CNV (type 2 or type 3) (P=0.020). CONCLUSION There is an association between posterior vitreous attachment and AMD. There is also an increased incidence of VMA with intra-retinal CNV. PMID:28251084

  4. Decreased Thickness and Integrity of the Macular Elastic Layer of Bruch’s Membrane Correspond to the Distribution of Lesions Associated with Age-Related Macular Degeneration

    PubMed Central

    Chong, N.H. Victor; Keonin, Jason; Luthert, Phil J.; Frennesson, Christina I.; Weingeist, David M.; Wolf, Rachel L.; Mullins, Robert F.; Hageman, Gregory S.

    2005-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch’s membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease. PMID:15632016

  5. Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related Macular Degeneration.

    PubMed

    Cipriani, Valentina; Hogg, Ruth E; Sofat, Reecha; Moore, Anthony T; Webster, Andrew R; Yates, John R W; Fletcher, Astrid E

    2017-09-01

    C-reactive protein (CRP) is a circulating inflammatory marker associated with late age-related macular degeneration (AMD). It remains uncertain whether the association between CRP concentrations and AMD is causal. To assess whether CRP (OMIM 123260) single-nucleotide polymorphisms that influence circulating CRP concentrations are associated with late AMD. Participants in 2 UK, hospital-based, case-control studies (Cambridge AMD study and Moorfields Eye Hospital AMD study) and 1 pan-European, cross-sectional, population-based study (the European Eye [EUREYE] Study) were recruited between November 6, 2000, and April 30, 2007. Participants underwent dilated stereo-digital fundus photography graded according to the International Classification of Age-related Maculopathy and Macular Degeneration. There were 1727 cases of late AMD (1151 neovascular, 384 geographic atrophy, and 192 mixed [neovascular AMD and geographic atrophy]) and 1153 controls. Early AMD cases (n = 574) were included only from the EUREYE Study. Data analysis was performed from August 1 to November 30, 2016. Four common single-nucleotide polymorphisms (rs1205, rs1130864, rs1800947, and rs3093077) were selected based on demonstrated influence on circulating CRP concentrations in the literature. In one study, genotyping of rs3093077 failed, and rs1800947 was typed in only 1 study. A genetic multiplicative model was used for the association of single-nucleotide polymorphisms with late AMD adjusted for age and sex. Among the 1727 patients with late AMD, the mean (SD) age was 78.7 (7.4) years, and 668 (38.7%) were men. The mean (SD) age of the controls was 74.9 (7.0) years, and 510 (44.2%) were men. In the pooled results of all 3 studies, neither rs1205 (odds ratio [OR], 0.99; 95% CI, 0.86-1.14) nor rs1130864 (OR, 0.96; 95% CI, 0.83-1.11) was associated with late AMD. For geographic atrophy, rs1205 had an OR of 0.91 (95% CI, 0.74-1.13) and rs1130864 had an OR of 0.94 (95% CI, 0.76-1.16). For neovascular

  6. Impact of age related macular degeneration on quality of life

    PubMed Central

    Hassell, J B; Lamoureux, E L; Keeffe, J E

    2006-01-01

    Aims To describe the impact of age related macular degeneration (AMD) on quality of life and explore the association with vision, health, and demographic variables. Methods Adult participants diagnosed with AMD and with impaired vision (visual acuity <6/12) were assessed with the Impact of Vision Impairment (IVI) questionnaire. Participants rated the extent that vision restricted participation in activities affecting quality of life and completed the Short Form General Health Survey (SF‐12) and a sociodemographic questionnaire. Results The mean age of the 106 participants (66% female) was 83.6 years (range 64–98). One quarter had mild vision impairment, (VA<6/12–6/18) and 75% had moderate or severely impaired vision. Participants reported from at least “a little” concern on 23 of the 32 IVI items including reading, emotional health, mobility, and participation in relevant activities. Those with mild and moderate vision impairment were similarly affected but significantly different from those with severe vision loss (p<0.05). Distance vision was associated with IVI scores but not age, sex, or duration of vision loss. Conclusion AMD affects many quality of life related activities and not just those related to reading. Referral to low vision care services should be considered for people with mild vision loss and worse. PMID:16622089

  7. Stereotactic radiotherapy in neovascular age-related macular degeneration

    PubMed Central

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

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

    PubMed Central

    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

  9. Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration

    PubMed Central

    Grunin, Michelle; Hagbi-Levi, Shira-; Rinsky, Batya; Smith, Yoav; Chowers, Itay

    2016-01-01

    Mononuclear phagocytes (MPs), including monocytes/macrophages, play complex roles in age-related macular degeneration (AMD) pathogenesis. We reported altered gene-expression signature in peripheral blood mononuclear cells from AMD patients, and a chemokine receptor signature on AMD monocytes. To obtain comprehensive understanding of MP involvement, particularly in peripheral circulation in AMD, we performed global gene expression analysis in monocytes. We separated monocytes from treatment-naïve neovascular AMD (nvAMD) patients (n = 14) and age-matched controls (n = 15), and performed microarray and bioinformatics analysis. Quantitative real-time PCR was performed on other sets of nvAMD (n = 25), atrophic AMD (n = 21), and controls (n = 28) for validation. This validated microarray genes (like TMEM176A/B and FOSB) tested, including differences between nvAMD and atrophic AMD. We identified 2,165 differentially-expressed genes (P < 0.05), including 79 genes with log2 fold change ≥1.5 between nvAMD and controls. Functional annotation using DAVID and TANGO demonstrated immune response alterations in AMD monocytes (FDR-P <0.05), validated by randomized data comparison (P < 0.0001). GSEA, ISMARA, and MEME analysis found immune enrichment and specific involved microRNAs. Enrichment of differentially-expressed genes in monocytes was found in retina via SAGE data-mining. These genes were enriched in non-classical vs. classical monocyte subsets (P < 0.05). Therefore, global gene expression analysis in AMD monocytes reveals an altered immune-related signature, further implicating systemic MP activation in AMD. PMID:27374485

  10. Do blue light filters confer protection against age-related macular degeneration?

    PubMed

    Margrain, T H; Boulton, M; Marshall, J; Sliney, D H

    2004-09-01

    Age-related macular degeneration (AMD) is a major health problem in the developed world accounting for approximately half of all blind registrations. Current treatment options are unsuitable for the majority of patients and therefore the identification of modifiable risk factors that may inform disease prevention programmes is a priority. This review evaluates the long-held belief that blue light exposure has a role in the pathogenesis of AMD. Laboratory evidence has demonstrated that photochemical reactions in the oxygen-rich environment of the outer retina lead to the liberation of cytotoxic reactive oxygen species (ROS). These ROS cause oxidative stress which is known to contribute to the development of AMD. The precise chromopore that may be involved in the pathogenesis of AMD is unclear but the age pigment lipofuscin is a likely candidate. Its aerobic photoreactivity and adverse effects on antioxidant activity combined with its gradual accumulation over time suggests that its in vivo phototoxicity increases with age despite changes in the absorption characteristics of the crystalline lens. Evidence from animal studies confirms blue light's damaging potential but the results are not directly applicable to macular degeneration in humans. Studies of human macular pigment density and the risk of AMD progression following cataract surgery lend further weight to the hypothesis that blue light exposure has a role in the pathogenesis of AMD but the epidemiological evidence is equivocal. On balance the evidences suggests but does not yet confirm that blue light is a risk factor for AMD. Given the socio-economic impact of this disease and urgent need to identify modifiable risk factors, future work should include a large-scale clinical trial to evaluate the effect of blue blocking filters on AMD progression rates. Copyright 2004 Elsevier Ltd.

  11. The prevalence of age-related macular degeneration in Alzheimer's disease.

    PubMed

    Williams, Michael A; Silvestri, Vittorio; Craig, David; Passmore, A Peter; Silvestri, Giuliana

    2014-01-01

    Age-related macular degeneration (AMD) and Alzheimer's disease (AD) share several features, including the presence of extracellular abnormal deposits associated with neuronal degeneration, drusen, and plaques, respectively. Investigation of any association of AMD and specifically AD is worthwhile but has rarely been done. The aim of this study was to determine the prevalence of AMD in subjects with AD in comparison with an age-matched cognitively normal cohort. Cases were defined as those diagnosed with AD using standardized criteria as part of their clinical care, while controls were cognitively intact individuals aged 65 years or more. Dilated retinal photographs were taken, and a range of potentially confounding factors measured including APOE genotype. AMD features were recorded and AMD grades given. Data was collected on 322 controls and 258 cases. While AMD was associated with AD, and the proportion of cases of advanced AMD in AD cases was twice that of controls, when corrected the association was lost. AD was associated with age, the presence of an APOE allele, and smoking, while being 'generally unwell recently' was associated with a reduced risk of AD. AD and AMD are both associated with age, but our study does not find evidence they are associated with each other. However the retina offers an opportunity to non-invasively image neuronal tissue, and more sophisticated imaging techniques may shed light on ocular biomarkers of AD.

  12. Measurement of the economic impact of visual impairment from age-related macular degeneration in Australia.

    PubMed

    Hopley, Charles; Carter, Rob; Mitchell, Paul

    2003-12-01

    The purpose of this report was to: (i) outline the potential value of health economic studies into age-related macular degeneration (AMD); (ii) provide an overview of health economic studies pertinent to AMD; and (iii) outline the basic frame work of cost-of-illness studies (a useful first step in applying economic methods). The detection and management of sensory loss in the elderly plays a key role in the Australian Government's Healthy Ageing Strategy. Age-related macular degeneration is currently the leading cause of blindness in elderly Australians. Although a large proportion of AMD cases remain untreatable, the introduction of photo-dynamic therapy provides a relatively expensive and possibly cost-effective innovation for others. Antioxidant therapy has also been proven effective in reducing progression of early to late disease. The discipline of economics can contribute to an understanding of AMD prevention and treatment through: (i) describing the current burden of disease; (ii) predicting the changes in the burden of disease over time, and (iii) evaluating the efficiency of different interventions. Cost-of-illness studies have been performed in many fields of medicine. Little work, however, has been done on describing the economic impact from AMD. A number of different economic evaluation methods can be used in judging the efficiency of possible interventions to reduce the disease burden of AMD. Although complementary in nature, each has specific uses and limitations. Studies of the economic impact of eye diseases are both feasible and necessary for informed health care decision-making.

  13. STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration

    PubMed Central

    Chen, Mei; Lechner, Judith; Zhao, Jiawu; Toth, Levente; Hogg, Ruth; Silvestri, Giuliana; Kissenpfennig, Adrien; Chakravarthy, Usha; Xu, Heping

    2016-01-01

    Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular age-related macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laser-induced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD. PMID:27009107

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

    PubMed Central

    Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    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. PMID:28243361

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

    PubMed

    Matsuura, Toshiyuki; Takayama, Kei; Kaneko, Hiroki; Ye, Fuxiang; Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    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.

  16. The Role of the Immune Response in Age-Related Macular Degeneration

    PubMed Central

    Whitcup, Scott M.; Atkinson, John P.; Rohrer, Bärbel; Dick, Andrew D.

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD. PMID:23762772

  17. Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment.

    PubMed

    Cheung, C M G; Wong, T Y

    2014-08-01

    Age-related macular degeneration (AMD) is a common vision-threatening condition affecting the elderly. AMD shares common risk factors and processes, including vascular and inflammatory pathways, with many systemic disorders. Associations have been reported between AMD and hypertension, cardiovascular disease, cerebrovascular disease, dyslipidaemia, chronic kidney disease and neurodegenerative disorders. An increasing amount of evidence suggests that individuals with AMD are also at risk of systemic diseases such as stroke. In this review, we summarize the latest evidence to support the notion that AMD is an ocular manifestation of systemic disease processes, and discuss the potential systemic side effects of ocular AMD therapy of which general physicians should be aware. Recent genetic discoveries and understanding of the pathogenic pathways in AMD in relation to systemic disorders are also highlighted. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  18. Electrophysiological changes after 360° retinotomy and macular translocation for subfoveal choroidal neovascularisation in age related macular degeneration

    PubMed Central

    Luke, C.; Aisenbrey, S.; Luke, M.; Marzella, G.; Bartz-Schmidt, K. U.; Walter, P.

    2001-01-01

    AIM—To evaluate electrophysiological changes after 360° retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age related macular degeneration (AMD).
METHODS—A consecutive series of 32 patients suffering from subfoveal choroidal neovascularisation secondary to AMD underwent 360° retinotomy and macular translocation. The ERG served as the main parameter of the study and was recorded 1 day before the translocation surgery and no earlier than 4 weeks after the silicone oil removal.
RESULTS—The scotopic ERG amplitudes were significantly reduced after translocation surgery. Depending on the applied flash luminance the mean b-wave amplitude reduction of the scotopic ERG varied between 67% (0.2 cd.s/m2) and 74% (0.03 cd.s/m2). The a-waves and b-waves of the saturating light response decreased significantly by 46% and 59%, respectively. The photopic a-wave and b-wave amplitudes were significantly lower after the translocation surgery resulting in a mean reduction of 27% and 43%, respectively.
CONCLUSIONS—Although macular translocation may provide the potential of preserving and even restoring vision in patients with subfoveal choroidal neovascular membranes secondary to AMD the present study indicates that a significant electrophysiological decrease is caused by surgical procedures associated with this technique. Further research is necessary to clarify if certain modifications of the surgical procedure are able to substantially reduce the neuroretinal trauma.

 PMID:11466247

  19. Risk factors for age-related macular degeneration in elderly Chinese population in Shenyang of China.

    PubMed

    Jia, LiHong; Shen, XueLi; Fan, Rui; Sun, Yan; Pan, XingYue; Yanh, HongMei; Liu, Lu

    2011-10-01

    The paper aims to evaluate the risk factors for age-related macular degeneration (AMD) in elderly Chinese population in Shenyang, a northeast city of China. A case-control study was conducted to investigate the risk factors for the prevalence of AMD. Ninety three AMD patients diagnosed by a complete ophthalmic examination were recruited as cases from the outpatient departments of two eye hospitals in Shenyang, while 108 normal subjects of similar age and sex were recruited as controls. A questionnaire was administered among both cases and controls. AMD patients aged 60 years and older accounted for 75.3%. There were significantly higher educational levels, shorter smoking history, less sunlight exposure and cataract, and higher proportion of antioxidants intake in controls than in AMD patients. The frequency of intake of fruits, legumes, fish and shrimps was significantly higher in controls than in AMD patients. In a binary logistic regression analysis, smoking and cataract were the risk factors for AMD (OR: 4.44, 95% CI: 2.27-8.69; OR: 4.47, 95% CI: 2.26-8.85 respectively). The high educational background was a protective factor for AMD (OR: 0.761, 95% CI: 0.51-0.98). A low educational background, smoking and cataract are associated with a higher prevalence of AMD. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

  20. Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

    PubMed

    Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

    2010-11-03

    Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.

  1. Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration.

    PubMed

    Lechner, Judith; Chen, Mei; Hogg, Ruth E; Toth, Levente; Silvestri, Giuliana; Chakravarthy, Usha; Xu, Heping

    2015-11-17

    Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b(+) cells and CD16(hi)HLA-DR(-) neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4(+) T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b(+) cells and neutrophils are associated with nAMD and that reduced levels of CD4(+) T-cells are associated with the absence of subretinal fibrosis in nAMD.

  2. Case-control study of the risk factors for age related macular degeneration

    PubMed Central

    Chaine, G.; Hullo, A.; Sahel, J.; Soubrane, G.; Espinasse-Berrod, M.; Schutz, D.; Bourguignon, C.; Harpey, C.; Brault, Y.; Coste, M.; Moccatti, D.; Bourgeois, H.

    1998-01-01

    AIM—A case-control study was initiated to determine the risk factors for the development of age related macular degeneration (AMD).
METHODS—Study participants, who were all white, aged 50-85 years, and were recruited from private ophthalmology practices. Each practitioner enrolled patients with bilateral AMD, who were then matched with controls for sex and age. Environmental factors and systemic and ocular histories were screened. All patients had bilateral red-free fundus photographs and fluorescein angiography. Photographs were classified into pigment epithelium alterations, drusen, geographic atrophy, and exudative AMD. Statistical analysis included the identification of risk factors for AMD. A multivariate analysis was performed at the end of the study. Analysis included the entire study population and was carried out for each stage of AMD.
RESULTS—1844 controls were compared with 1844 patients with AMD. Mean age was 71 years for controls and 72 for cases. Logistic regression identified six major risk factors for AMD (whole population): arterial hypertension (odds ratio (OR) =1.28), coronary disease (OR=1.31), hyperopia (OR=1.33), light coloured irises (OR=1.22), and lens opacities or previous cataract surgery (OR=1.55). The significance of vascular risk factors was increased for late stages of AMD, especially the atrophic forms (coronary disease, OR=3.19).
CONCLUSIONS—This large case-control study confirms some of the risk factors previously identified and may contribute to the determination of methods for prevention of AMD.

 Keywords: age related macular degeneration; risk factors; case-control study PMID:9893587

  3. Present and future treatment possibilities in macular degeneration

    NASA Astrophysics Data System (ADS)

    Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

    2005-11-01

    Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  6. Serum autoantibody biomarkers for age-related macular degeneration and possible regulators of neovascularization.

    PubMed

    Morohoshi, Kei; Patel, Nishal; Ohbayashi, Masaharu; Chong, Victor; Grossniklaus, Hans E; Bird, Alan C; Ono, Santa J

    2012-02-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Its pathogenesis is at least partially mediated by immunological factors, including a possible autoimmune response. To date, only a few antibodies have been identified in sera from patients with AMD. In order to reveal an autoantibody profile for AMD and identify biomarkers for progression of this disease, we have performed an antigen microarray analysis of serum samples from patients with AMD and healthy controls. Sera from the AMD groups contained high levels of IgG and IgM autoantibodies to some systemic antigens when compared to the normal group. Targeted antigens included cyclic nucleotide phosphodiesterase, phosphatidylserine (PS) and proliferating cell nuclear antigen. The IgG/IgM ratio for antibodies to PS was notably elevated in the AMD group compared to the normal group, and this ratio correlated best with the stage of AMD patients with an anti-PS ratio greater than the cut-off value had a 44-fold risk for advanced AMD with choroidal neovascularization. PS immunoreactivity was also elevated in AMD retina. Moreover, IgG autoantibodies purified from sera of AMD patients induced more tube formation on choroidal-retinal endothelial cells compared to those of healthy donors. Hence, sera from patients with AMD contain specific autoantibodies which may be used as biomarkers for AMD, and the IgG/M ratio for autoantibodies to PS might allow better monitoring of AMD progression. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Bioptic Telescope Use and Driving Patterns of Drivers with Age-Related Macular Degeneration

    PubMed Central

    Bowers, Alex R.; Sheldon, Sarah S.; DeCarlo, Dawn K.; Peli, Eli

    2016-01-01

    Purpose To investigate the telescope use and driving patterns of bioptic drivers with age-related macular degeneration (AMD). Methods A questionnaire addressing telescope use and driving patterns was administered by telephone interview to three groups of bioptic drivers: AMD (n = 31; median 76 years); non-AMD first licensed with a bioptic (n = 38; 53 years); and non-AMD first licensed without a bioptic (n = 47; 37 years). Driving patterns of bioptic AMD drivers were also compared with those of normal vision (NV) drivers (n = 36; 74 years) and nonbioptic AMD drivers (n = 34; 79 years). Results Bioptic usage patterns of AMD drivers did not differ from those of the younger bioptic drivers and greater visual difficulty without the bioptic was strongly correlated with greater bioptic helpfulness. Bioptic AMD drivers were more likely to report avoidance of night driving than the age-similar NV drivers (P = 0.06). However, they reported less difficulty than the nonbioptic AMD drivers in all driving situations (P ≤ 0.02). Weekly mileages of bioptic AMD drivers were lower than those of the younger bioptic drivers (P < 0.001), but not the NV group (P = 0.54), and were higher than those of the nonbioptic AMD group (P < 0.001). Conclusions Our results suggest that bioptic telescopes met the visual demands of drivers with AMD and that those drivers had relatively unrestricted driving habits. Translational Relevance Licensure with a bioptic telescope may prolong driving of older adults with AMD; however, objective measures of bioptic use, driving performance, and safety are needed. PMID:27642541

  8. Bioptic Telescope Use and Driving Patterns of Drivers with Age-Related Macular Degeneration.

    PubMed

    Bowers, Alex R; Sheldon, Sarah S; DeCarlo, Dawn K; Peli, Eli

    2016-09-01

    To investigate the telescope use and driving patterns of bioptic drivers with age-related macular degeneration (AMD). A questionnaire addressing telescope use and driving patterns was administered by telephone interview to three groups of bioptic drivers: AMD (n = 31; median 76 years); non-AMD first licensed with a bioptic (n = 38; 53 years); and non-AMD first licensed without a bioptic (n = 47; 37 years). Driving patterns of bioptic AMD drivers were also compared with those of normal vision (NV) drivers (n = 36; 74 years) and nonbioptic AMD drivers (n = 34; 79 years). Bioptic usage patterns of AMD drivers did not differ from those of the younger bioptic drivers and greater visual difficulty without the bioptic was strongly correlated with greater bioptic helpfulness. Bioptic AMD drivers were more likely to report avoidance of night driving than the age-similar NV drivers (P = 0.06). However, they reported less difficulty than the nonbioptic AMD drivers in all driving situations (P ≤ 0.02). Weekly mileages of bioptic AMD drivers were lower than those of the younger bioptic drivers (P < 0.001), but not the NV group (P = 0.54), and were higher than those of the nonbioptic AMD group (P < 0.001). Our results suggest that bioptic telescopes met the visual demands of drivers with AMD and that those drivers had relatively unrestricted driving habits. Licensure with a bioptic telescope may prolong driving of older adults with AMD; however, objective measures of bioptic use, driving performance, and safety are needed.

  9. Awareness of Age-related Macular Degeneration and Its Risk Factors among Beijing Residents in China

    PubMed Central

    Zhang, Chen-Xi; Zhang, Gu-Muyang; Ma, Nan; Xia, Song; Yang, Jing-Yuan; Chen, You-Xin

    2017-01-01

    Background: Age-related macular degeneration (AMD) is a major cause of irreversible blindness, and awareness of this disease is important in the prevention of blindness. However, lack of public awareness of AMD was shown in previous studies, and there was no report of AMD awareness in the Mainland of China. Therefore, the aim of our study was to assess the awareness of AMD and its risk factors among Beijing residents in China. Methods: A cross-sectional, computer-assisted, telephone investigation was conducted to measure the awareness of AMD among Beijing residents. All the contacts of potential respondents were randomly generated by computer. Only those above 18 years of age and willing to participate in the study were included. The questionnaire for the study was modified from the AMD Alliance International Global Report. Pearson's Chi-square test and binary logistic regression analysis were used to identify the factors that affected the knowledge of AMD. Results: Among 385 Beijing residents who agreed to participate, the awareness of AMD was 6.8%, far below than that of cataract and glaucoma. Participants who were above 30 years of age (odds ratio [OR] 6.17, confidence interval [CI] 1.44–26.57), with experience of health-related work (OR 8.11, CI 3.25–20.27), and whose relatives/friends or themselves suffering from AMD (OR 32.18, CI 11.29–91.68) had better AMD awareness. Among those familiar with AMD, only 35% of them identified smoking as a risk factor, and only 23.1% of the residents believed that smoking could lead to blindness. Conclusions: The sample of Chinese population had limited knowledge of AMD. Educational programs need to be carried out to raise public awareness of AMD. PMID:28091406

  10. Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.

    PubMed

    Kalayoglu, Murat V; Bula, Deisy; Arroyo, Jorge; Gragoudas, Evangelos S; D'Amico, Donald; Miller, Joan W

    2005-11-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

  11. Visual hallucinations in patients with macular degeneration.

    PubMed

    Holroyd, S; Rabins, P V; Finkelstein, D; Nicholson, M C; Chase, G A; Wisniewski, S C

    1992-12-01

    This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory.

  12. Increased serum IgA concentration and plasmablast frequency in patients with age-related macular degeneration.

    PubMed

    Yu, Honghua; Yuan, Ling; Yang, Yahan; Ma, Suihong; Peng, Lianghong; Wang, Yong; Zhang, Chu; Li, Tao

    2016-05-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among senior citizens of developed countries, with currently unknown etiology. Despite the close associations between AMD development and inhibitory complement factor H mutations, the first step of complement activation, which is the antibody response in AMD patients, has not been studied. Here, we obtained blood and tear samples from AMD patients and Non-AMD controls. We found that compared to Non-AMD controls, AMD subjects had increased IgA titers in serum and tear, and had elevated levels of circulating antibody-secreting plasmablasts. The increase in antibody titer was limited to the IgA isotype, since no significant differences were observed in IgM and IgG isotypes between AMD patients and Non-AMD controls. Interestingly, this increased antibody response in AMD patients was correlated with disease severity, as late AMD patients had increased IgA titers in serum and tear, as well as elevated plasmablast frequency after staphylococcal enterotoxin B stimulation, compared to early AMD patients. Together, our results implicated a role of overreactive IgA responses in AMD pathogenesis. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration

    PubMed Central

    Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

    2012-01-01

    Purpose To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). Methods The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. Results In the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149±0.105 logMAR units, which significantly improved to 0.69±0.06 logMAR units at 1 year (P<0.001). This BCVA was maintained at 0.633±0.083 logMAR units on their final examination. In the 17 eyes with mCNV followed for ≥5 years, the mean preoperative BCVA was 1.083±0.119 logMAR units, which was significantly improved to 0.689±0.121 logMAR units at 1 year (P=0.001). This BCVA was maintained at 0.678±0.142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Conclusions Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years. PMID:22173070

  14. Development of quantitative diagnostic observables for age-related macular degeneration using Spectral Domain OCT

    NASA Astrophysics Data System (ADS)

    Bower, Bradley A.; Chiu, Stephanie J.; Davies, Emily; Davis, Anjul M.; Zawadzki, Robert J.; Fuller, Alfred R.; Wiley, David F.; Izatt, Joseph A.; Toth, Cynthia A.

    2007-02-01

    We report on the development of quantitative, reproducible diagnostic observables for age-related macular degeneration (AMD) based on high speed spectral domain optical coherence tomography (SDOCT). 3D SDOCT volumetric data sets (512 x 1000 x 100 voxels) were collected (5.7 seconds acquisition time) in over 50 patients with age-related macular degeneration and geographic atrophy using a state-of-the-art SDOCT scanner. Commercial and custom software utilities were used for manual and semi-automated segmentation of photoreceptor layer thickness, total drusen volume, and geographic atrophy cross-sectional area. In a preliminary test of reproducibility in segmentation of total drusen volume and geographic atrophy surface area, inter-observer error was less than 5%. Extracted volume and surface area of AMD-related drusen and geographic atrophy, respectively, may serve as useful observables for tracking disease state that were not accessible without the rapid 3D volumetric imaging capability unique to retinal SDOCT.

  15. Wet age related macular degeneration management and follow-up.

    PubMed

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies.

  16. Measurement of Perceived Stress in Age-Related Macular Degeneration.

    PubMed

    Dougherty, Bradley E; Cooley, San-San L; Davidorf, Frederick H

    2017-03-01

    To validate the Perceived Stress Scale (PSS) in patients with age-related macular degeneration (AMD) using Rasch analysis. Study participants with AMD were recruited from the retina service of the Department of Ophthalmology at the Ohio State University during clinical visits for treatment or observation. Visual acuity with habitual distance correction was assessed. A 10-item version of the PSS was administered in large print or by reading the items to the patient. Rasch analysis was used to investigate the measurement properties of the PSS, including fit to the model, ability to separate between people with different levels of perceived stress, category response structure performance, and unidimensionality. A total of 137 patients with a diagnosis of AMD were enrolled. The mean (±SD) age of participants was 82 ± 9 years. Fifty-four percent were female. Median Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity of the better eye was 65 letters (Snellen 20/50), with a range of approximately 20/800 to 20/15. Forty-seven percent of participants were receiving an anti-VEGF injection on the day of the study visit. The response category structure was appropriate. One item, "How often have you felt confident in your ability to handle your personal problems?" was removed due to poor fit statistics. The remaining nine items showed good fit to the model, acceptable measurement precision as assessed by the Rasch person separation statistic, and unidimensionality. There was some evidence of differential item functioning by age and visual acuity. The Perceived Stress Scale demonstrated acceptable measurement properties and may be useful for the measurement of perceived stress in patients with AMD.

  17. Serum carotenoids and risk of age-related macular degeneration in a chinese population sample.

    PubMed

    Zhou, Haiying; Zhao, Xianfeng; Johnson, Elizabeth J; Lim, Apiradee; Sun, Erdan; Yu, Jie; Zhang, Yinbo; Liu, Xipu; Snellingen, Torkel; Shang, Fu; Liu, Ningpu

    2011-06-17

    It has been hypothesized that the macular carotenoids protect against age-related macular degeneration (AMD). In this study, the association between serum concentrations of carotenoids and the presence of AMD was evaluated in a case-control sample of elderly Chinese subjects. Two hundred sixty-three individuals aged between 50 and 88 years enrolled in the study. Subjects included 82 cases with exudative AMD, 92 cases with early AMD, and 89 control individuals. Serum carotenoids (lutein, zeaxanthin, lycopene, α- and β-carotenes, and β-cryptoxanthin) and retinol were measured with reversed-phase high-performance liquid chromatography (HPLC). Serum levels of carotenoids and retinol were significantly lower in the cases with exudative AMD than in the controls. Median levels of lutein and zeaxanthin were 0.538 and 0.101 μM, respectively, in the control subjects, and 0.488 and 0.076 μM, respectively, in cases with exudative AMD. After adjustment for age, sex, smoking status, and body mass index (BMI), a significant inverse association was observed for exudative AMD with serum zeaxanthin (relative risk ratio [RRR], 0.04; 95% confidence interval [CI], 0-0.35), lycopene (RRR, 0.22; 95% CI, 0.1-0.48), and α-carotene (RRR, 0.24; 95% CI, 0.12-0.51). Early AMD was inversely associated only with lycopene (RRR, 0.49; 95% CI, 0.28-0.86) but was positively associated with α-carotene (RRR, 2.22; 95% CI, 1.37-3.58). No significant associations were observed between serum lutein and cases with early or exudative AMD. The data suggest that higher levels of serum carotenoids, in particular zeaxanthin and lycopene, are associated with a lower likelihood of having exudative AMD. Serum levels of carotenoids were relatively higher in this Chinese cohort than in samples of other ethnicities in previous reports.

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

    PubMed Central

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

    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 factors and different AMD stages depending on unilateral and bilateral disease severity. Methods 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. Results 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 p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages 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). Conclusion 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

  19. Gene ontology and KEGG enrichment analyses of genes related to age-related macular degeneration.

    PubMed

    Zhang, Jian; Xing, ZhiHao; Ma, Mingming; Wang, Ning; Cai, Yu-Dong; Chen, Lei; Xu, Xun

    2014-01-01

    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.

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

    PubMed Central

    Schleicher, Molly; Weikel, Karen; Garber, Caren; Taylor, Allen

    2013-01-01

    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. PMID:23820727

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration.

    PubMed

    Johnson, Elizabeth J; Schaefer, Ernst J

    2006-06-01

    Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily.

  3. [The pharmacogenomics of CFH Y402H and wet age-related macular degeneration].

    PubMed

    Chen, L L; Chen, Y Y

    2017-02-11

    Age-related macular degeneration(AMD) is one of the main leading causes of irreversible vision damage in patients over 50 years old. Genetic factors play an important role in the occurrence and development of AMD. Since the significant correlation between complement factor H (CFH) gene and AMD was found, the pharmacogenomics of CFH polymorphism was paid close attention by academic circles. Among which, studies concerning CFH Y402H were more deeply. Studies have found CFH Y402H genotypes might lead to differences toward the outcome of PDT and anti-VEGF treatment. In this article, we review the researches on the pharmacogenomics of CFH Y402H in wet AMD treatment. (Chin J Ophthalmol, 2017, 53: 144-147).

  4. Current knowledge on reticular pseudodrusen in age-related macular degeneration.

    PubMed

    Alten, F; Eter, N

    2015-06-01

    Drusen are focal deposits of extracellular material located between the retinal pigment epithelium (RPE) and Bruch's membrane and represent the major phenotypic characteristic of age-related macular degeneration (AMD). Due to evolving imaging techniques and recent histological studies, reticular pseudodrusen (RPD) have received increasing attention and have been recently identified as an additional phenotypic entity in AMD. In contrast to conventional drusen, RPD proved to be located internal to the RPE. In the past few years, numerous studies collected new findings on RPD related to their pathogenesis, imaging properties and impact on retinal function. While most former natural history studies as well as interventional studies in early AMD did not include imaging RPD beyond colour fundus photography, this phenotype must be included in every future large-scale study on AMD. This review summarises the current knowledge on RPD.

  5. Choroid, Haller's, and Sattler's Layer Thickness in Intermediate Age-Related Macular Degeneration With and Without Fellow Neovascular Eyes

    PubMed Central

    Esmaeelpour, Marieh; Ansari-Shahrezaei, Siamak; Glittenberg, Carl; Nemetz, Susanne; Kraus, Martin F.; Hornegger, Joachim; Fujimoto, James G.; Drexler, Wolfgang; Binder, Susanne

    2014-01-01

    Purpose. To analyze choroidal, Sattler's, and Haller's layer thickness maps in age-related macular degeneration (AMD) patients having eyes with bilateral large drusen and pigment changes (intermediate AMD), in patients having intermediate AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). Methods. Automatically generated choroidal thickness (ChT), retinal thickness, and Sattler's and Haller's layer thickness maps were statistically analyzed in 67 subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36° × 36° field of view. Results. The mean ± SD (μm) subfoveal ChT for healthy subjects and for bilateral intermediate AMD, unilateral intermediate AMD, and their nAMD fellow eyes was 259 ± 95 and 222 ± 98, 149 ± 60, and 171 ± 78, respectively. Choroidal thickness maps demonstrated significant submacular thinning in unilateral intermediate AMD in comparison to healthy and bilateral intermediate AMD eyes (P < 0.001, ANOVA, post hoc P < 0.001 and P < 0.05, respectively). Sattler's and Haller's layers were thinnest in intermediate AMDs that presented with nAMD fellow eyes (Kruskal-Wallis test P < 0.01). For the choroid and its sublayers, there was no difference between the intermediate AMD eyes and their fellow nAMD eyes (paired testing, P < 0.05). Conclusions. The 3D 1060-nm OCT choroidal imaging visualized significant changes in choroidal, Sattler's, and Haller's layer thickness in relation to the progression of AMD. This may be important for understanding the choroidopathy in the pathophysiology of AMD. PMID:25052997

  6. The Macular Degeneration and Aging Study: Design and Research Protocol of a Randomized Trial for a Psychosocial Intervention with Macular Degeneration Patients

    PubMed Central

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

    2015-01-01

    Age-related Macular Degeneration (AMD) is the leading cause of irreversible and predictable blindness among older adults and creates serious physical and mental health consequences for this population. 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) is 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. PMID:25812482

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

    PubMed

    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.

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

    PubMed

    Schick, Tina; Ersoy, Lebriz; Lechanteur, Yara T E; Saksens, Nicole T M; Hoyng, Carel B; den Hollander, Anneke I; Kirchhof, Bernd; Fauser, Sascha

    2016-04-01

    To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). 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 about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.

  9. Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

    PubMed

    McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

    2014-12-18

    To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  10. Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes.

    PubMed

    Thompson, Cheryl L; Klein, Barbara E K; Klein, Ronald; Xu, Zhiying; Capriotti, Jennifer; Joshi, Tripti; Leontiev, Dmitry; Lee, Kristine E; Elston, Robert C; Iyengar, Sudha K

    2007-09-01

    In this study, we investigated the associations of complement factor H (CFH) and hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales, measuring the course of AMD and drusen development, were examined in two samples: the Family Age-Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that its role is not phenotype-specific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD. The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (P = 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR [beta = -0.90 (P = 0.022)]. Associations between rs743137 (P = 0.05) and rs680638 (P = 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal pathophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.

  11. Genome-wide analysis of copy number variants in age-related macular degeneration

    PubMed Central

    Meyer, Kacie J.; Davis, Lea K.; Schindler, Emily I.; Beck, John S.; Rudd, Danielle S.; Grundstad, A. Jason; Scheetz, Todd E.; Braun, Terry A.; Fingert, John H.; Alward, Wallace L.; Kwon, Young H.; Folk, James C.; Russell, Stephen R.; Stone, Edwin M.; Sheffield, Val C.

    2012-01-01

    Age-related macular degeneration (AMD) is a complex genetic disease, with many loci demonstrating appreciable attributable disease risk. Despite significant progress toward understanding the genetic and environmental etiology of AMD, identification of additional risk factors is necessary to fully appreciate and treat AMD pathology. In this study, we investigated copy number variants (CNVs) as potential AMD risk variants in a cohort of 400 AMD patients and 500 AMD-free controls ascertained at the University of Iowa. We used three publicly available copy number programs to analyze signal intensity data from Affymetrix® GeneChip SNP Microarrays. CNVs were ranked based on prevalence in the disease cohort and absence from the control group; high interest CNVs were subsequently confirmed by qPCR. While we did not observe a single-locus “risk CNV” that could account for a major fraction of AMD, we identified several rare and overlapping CNVs containing or flanking compelling candidate genes such as NPHP1 and EFEMP1. These and other candidate genes highlighted by this study deserve further scrutiny as sources of genetic risk for AMD. PMID:20981449

  12. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans.

    PubMed

    Al Gwairi, Othman; Thach, Lyna; Zheng, Wenhua; Osman, Narin; Little, Peter J

    2016-01-01

    Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD.

  13. Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways.

    PubMed

    Logue, Mark W; Schu, Matthew; Vardarajan, Badri N; Farrell, John; Lunetta, Kathryn L; Jun, Gyungah; Baldwin, Clinton T; Deangelis, Margaret M; Farrer, Lindsay A

    2014-06-01

    Several lines of inquiry point to overlapping molecular mechanisms between late-onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We evaluated summarized results from large genome-wide association studies for AD and AMD to test the hypothesis that AD susceptibility loci are also associated with AMD. We observed association of both disorders with genes in a region of chromosome 7, including PILRA and ZCWPW1 (peak AMD SNP rs7792525, minor allele frequency [MAF] = 19%, odds ratio [OR] = 1.14, p = 2.34 × 10(-6)), and with ABCA7 (peak AMD SNP rs3752228, MAF = 0.054, OR = 1.22, p = 0.00012). Next, we evaluated association of AMD with genes in AD-related pathways identified by canonical pathway analysis of AD-associated genes. Significant associations were observed with multiple previously identified AMD risk loci and 2 novel genes: HGS (peak SNP rs8070488, MAF = 0.23, OR = 0.91, p = 7.52 × 10(-5)), which plays a role in the clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590, MAF = 0.34, OR = 0.89, p = 1.17 × 10(-5)), which is a member of the atherosclerosis signaling and the LXR/RXR activation pathways. Our results suggest that AMD and AD share genetic mechanisms.

  14. The role of omega-3 and micronutrients in age-related macular degeneration.

    PubMed

    Querques, Giuseppe; Souied, Eric H

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD.

  15. Area deprivation and age related macular degeneration in the EPIC-Norfolk Eye Study.

    PubMed

    Yip, Jennifer L Y; Khawaja, Anthony P; Chan, Michelle P Y; Broadway, David C; Peto, Tunde; Luben, Robert; Hayat, Shabina; Bhaniani, Amit; Wareham, Nick; Foster, Paul J; Khaw, Kay-Tee

    2015-02-01

    To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). Cross sectional study nested within a longitudinal cohort study. Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7-13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36-0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Area deprivation and age related macular degeneration in the EPIC-Norfolk Eye Study

    PubMed Central

    Yip, Jennifer L.Y.; Khawaja, Anthony P.; Chan, Michelle P.Y.; Broadway, David C.; Peto, Tunde; Luben, Robert; Hayat, Shabina; Bhaniani, Amit; Wareham, Nick; Foster, Paul J.; Khaw, Kay-Tee

    2015-01-01

    Objectives To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). Study design Cross sectional study nested within a longitudinal cohort study. Methods Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. Results 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7–13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36–0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. Conclusions The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD. PMID:25687711

  17. Nutritional and smoking advice recalled by patients attending a UK age-related macular degeneration clinic.

    PubMed

    Bott, Deborah; Huntjens, Byki; Binns, Alison

    2017-09-11

    Age-related macular degeneration (AMD) is responsible for half of registered visual impairment in the UK. The Royal College of Ophthalmologists recommends providing guidance to people with AMD regarding smoking, diet, and nutritional supplements. The aim of this study was to investigate lifestyle advice recalled by patients with neovascular AMD (nAMD). The study took place at a UK hospital outpatients' clinic. Eligible patients with unilateral nAMD were presented with a survey about lifestyle advice provision. Of 248 respondents, only 39.9% remembered receiving advice regarding diet at the hospital. Only 24.2% of respondents recalled receiving advice regarding nutritional supplements, and only 19.8% of respondents started taking daily supplements as a result of their AMD. The most prevalent reason for not taking supplements amongst those advised to do so was lack of understanding of how it would help their eyes. Nearly 13% of the sample reported currently smoking, 53.1% of which reported that they were advised to stop smoking when diagnosed with AMD. The findings suggest that it would be beneficial to review the provision of lifestyle advice to patients attending AMD outpatients' clinics, and to consider whether advice is being provided in an optimal format for later recall.

  18. Management of Neovascular Age-related Macular Degeneration: A Review on Landmark Randomized Controlled Trials

    PubMed Central

    Agarwal, Aniruddha; Aggarwal, Kanika; Gupta, Vishali

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti-vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground-breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized. PMID:26957836

  19. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans

    PubMed Central

    Thach, Lyna; Zheng, Wenhua; Osman, Narin

    2016-01-01

    Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD. PMID:27563459

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

    PubMed Central

    Wang, Yafeng; Wang, Mingxu; Zhang, Xiaoqing; Zhang, Qianyu; Nie, Jing; Zhang, Ming; Liu, Xiaohong; Ma, Le

    2016-01-01

    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. PMID:27782072

  1. Management of Neovascular Age-related Macular Degeneration: A Review on Landmark Randomized Controlled Trials.

    PubMed

    Agarwal, Aniruddha; Aggarwal, Kanika; Gupta, Vishali

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti-vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground-breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized.

  2. A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

    USDA-ARS?s Scientific Manuscript database

    We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

  3. Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

    USDA-ARS?s Scientific Manuscript database

    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...

  4. Stem cell-based therapies for age-related macular degeneration: current status and prospects

    PubMed Central

    Mu, Yalin; Zhao, Manli; Su, Guangming

    2014-01-01

    Abstract: Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness both in developed and developing countries. During the past decades, the managements of neovascular AMD (wet AMD) have dramatically progressed. However, still no effective treatment for non-neovascular AMD (dry AMD) which was characterized by geographic macular atrophy. Recent advances in stem cell sciences have demonstrated that retinal pigment epithelium (RPE) cells can be generated from several types of stem cells (including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, et al) by cell co-culturing or defined factors. Additionally, studies also showed that visual function could be recovered by transplantation of these cells into subretinal space in vivo. Moreover, the United States Food and Drug Administration already approved several clinical trials to evaluate the efficiencies of stem cell based cell transplantation for dry AMD patients. Till now, a few patients enrolled in these studies achieved promising outcomes. This review will summarize recent advances in stem cell based RPE differentiation, transplantation, and the preliminary results of clinical trials. The obstacles and prospects in this field will also be discussed. PMID:25550892

  5. Prediction of Age-related Macular Degeneration in the General Population

    PubMed Central

    Buitendijk, Gabriëlle H.S.; Elena, Rochtchina; Myers, Chelsea; van Duijn, Cornelia M.; Lee, Kristine E.; Klein, Barbara E.K.; Meuer, Stacy M.; de Jong, Paulus T.V. M.; Holliday, Elizabeth G.; Tan, Ava G.; Uitterlinden, André G.; Sivakumaran, Theru A.; Attia, John; Hofman, Albert; Mitchell, Paul; Vingerling, Johannes R.; Iyengar, Sudha K.; Janssens, A.Cecile J.W.; Wang, Jie Jin; Klein, Ronald; Klaver, Caroline C.W.

    2013-01-01

    Purpose Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies. Design Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC). Participants People (n = 10106) with gradable fundus photographs, genotype data, and follow-up data without late AMD at baseline. Methods Features of AMD were graded on fundus photographs using the 3CC AMD severity scale. Associations with known genetic and environmental AMD risk factors were tested using Cox proportional hazard analysis. In the RS, the prediction of AMD was estimated for multivariate models by area under receiver operating characteristic curves (AUCs). The best model was validated in the BDES and BMES, and associations of variables were re-estimated in the pooled data set. Beta coefficients were used to construct a risk score, and risk of incident late AMD was calculated using Cox proportional hazard analysis. Cumulative incident risks were estimated using Kaplan–Meier product-limit analysis. Main Outcome Measures Incident late AMD determined per visit during a median follow-up period of 11.1 years with a total of 4 to 5 visits. Results Overall, 363 participants developed incident late AMD, 3378 participants developed early AMD, and 6365 participants remained free of any AMD. The highest AUC was achieved with a model including age, sex, 26 single nucleotide polymorphisms in AMD risk genes, smoking, body mass index, and baseline AMD phenotype. The AUC of this model was 0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.02 (95% confidence interval [CI], 0.01–0.04) to develop late AMD, and individuals with high

  6. Visual Function and Its Relationship with Severity of Early, and Activity of Neovascular, Age-Related Macular Degeneration

    PubMed Central

    Loughman, James; Sabour-Pickett, Sarah; Nolan, John M.; Klein, Barbara; Klein, Ronald; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between visual function and severity of early age-related macular degeneration (AMD) and activity of neovascular (nv-) AMD. Methods The following data was collected from 66 eyes of 66 subjects with early AMD and 47 eyes of 47 subjects with active nv-AMD: corrected distance visual acuity (CDVA); contrast sensitivity (CS); glare disability (GD); and retinotopic ocular sensitivity (ROS) of the central 5° of the retina, by microperimetry. Fundus photographic grading of early AMD was performed in a masked fashion. Mean foveal thickness (MFT) was measured by spectral domain optical coherence tomography in patients with nv-AMD. Results In subjects with early AMD, there was an inverse and statistically significant relationship between measures of ROS within the central 5° of retina (including fixation) and severity of early AMD (p=0.01). In eyes with active nv-AMD, an inverse and statistically significant relationship was observed between measures of MFT and measures of ROS at the central 5° of retina (r=-0.34; p=0.02). No other measures, including CDVA, were significantly related to severity of early AMD, or to MFT in nv-AMD. Conclusion Although ROS was cross-sectionally associated with disease severity, and inversely related to MFT, an important determinant of need-to-treat in cases of nv-AMD, further research is required to determine the appropriateness of ROS for monitoring early and active neovascular forms of this disease.

  7. Vascular-targeted photodynamic therapy in the treatment of neovascular age-related macular degeneration: Clinical perspectives.

    PubMed

    Kawczyk-Krupka, A; Bugaj, A M; Potempa, M; Wasilewska, K; Latos, W; Sieroń, A

    2015-06-01

    Vascular targeted photodynamic therapy (VTP), with use of verteporfin as a photosensitizer is one of the few therapies, which has been shown to effectively slow the progression of the "wet" form of age-related macular degeneration (AMD), and even to stabilize visual acuity over many years. Although, due to considerable advance of AMD treatment, it is currently not recommended in monotherapy of AMD, however, its combination with steroids and anti-angiogenic biologic drugs may reveal high therapeutic potential in the treatment of neovascular AMD. The future of VTP as a method of AMD treatment is development of new selective and targeted photosensitizer and combination of this method with other therapeutic strategies targeting cellular structures or pathways involved in AMD progression.

  8. Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials.

    PubMed

    Jaffe, Glenn J; Martin, Daniel F; Toth, Cynthia A; Daniel, Ebenezer; Maguire, Maureen G; Ying, Gui-Shuang; Grunwald, Juan E; Huang, Jiayan

    2013-09-01

    To describe the effects of treatment for 1 year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity (VA) in eyes with neovascular age-related macular degeneration (AMD). Prospective cohort study within a randomized clinical trial. Participants in the Comparison of Age-related Macular Degeneration Treatments Trials. Participants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as-needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and VA testing were performed periodically throughout 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes. Fluid type and location and thickness by OCT, size, and lesion composition on FP, FA, and VA. Intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and retinal, subretinal, and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks, and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 μm) or thick (>212 μm) retinas had worse VA than those with normal thickness (120-212 μm). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features. Anti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA

  9. Preserved retinotopic brain connectivity in macular degeneration.

    PubMed

    Haak, Koen V; Morland, Antony B; Rubin, Gary S; Cornelissen, Frans W

    2016-05-01

    The eye disease macular degeneration (MD) is a leading cause of blindness worldwide. There is no cure for MD, but several promising treatments aimed at restoring vision at the level of the retina are currently under investigation. These treatments assume that the patient's brain can still process appropriately the retinal input once it is restored, but whether this assumption is correct has yet to be determined. We used functional magnetic resonance imaging (fMRI) and connective field modelling to determine whether the functional connectivity between the input-deprived portions of primary visual cortex (V1) and early extrastriate areas (V2/3) is still retinotopically organised. Specifically, in both patients with juvenile macular degeneration and age-matched controls with simulated retinal lesions, we assessed the extent to which the V1-referred connective fields of extrastriate voxels, as estimated on the basis of spontaneous fMRI signal fluctuations, adhered to retinotopic organisation. We found that functional connectivity between the input-deprived portions of visual areas V1 and extrastriate cortex is still largely retinotopically organised in MD, although on average less so than in controls. Patients with stable fixation exhibited normal retinotopic connectivity, however, suggesting that for the patients with unstable fixation, eye-movements resulted in spurious, homogeneous signal modulations across the entire input-deprived cortex, which would have hampered our ability to assess their spatial structure of connectivity. Despite the prolonged loss of visual input due to MD, the cortico-cortical connections of input-deprived visual cortex remain largely intact. This suggests that the restoration of sight in macular degeneration can rely on a largely unchanged retinotopic representation in early visual cortex following loss of central retinal function. © 2016 The Authors Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of

  10. Dietary and lifestyle risk factors associated with age-related macular degeneration: A hospital based study

    PubMed Central

    Nidhi, Bhatiwada; Mamatha, Bangera Sheshappa; Padmaprabhu, Chamrajnagar Anantharajiah; Pallavi, Prabhu; Vallikannan, Baskaran

    2013-01-01

    Aim: To establish the frequency, associations and risk factors for age-related macular degeneration (AMD) in hospital population of South India. Materials and Methods: In this cross-sectional hospital based study, 3549 subjects (2090 men and 1459 women) above 45 years of age were screened randomly for AMD. Participants underwent ocular evaluation and were interviewed for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire. AMD was defined according to the international classifications and grading system. Results: Either form of AMD was detected in 77 (2.2%) participants. Of which, early and late AMD was present in 63 (1.8%) and 14 (0.4%) subjects, respectively. Binary logistic analysis showed that the incidence of AMD was significantly higher with increasing age (Odds ratio [OR] 1.17; 95% CI 1.13-1.22) and diabetes (OR 3.97; 95% CI 2.11-7.46). However, AMD was significant among heavy cigarette smokers (OR 5.58; 95% CI 0.88-7.51) and alcoholics (OR 4.85; 95% CI 2.45-12.22). Dietary lutein/zeaxanthin (L/Z) and β-carotene intake were associated (P < 0.001) with the reduction in risk for AMD, with an OR of 0.38 and 0.65, respectively. Conclusions: Higher dietary intake of carotenoids, especially L/Z, was associated with lower risk for AMD. Risk of AMD is higher with increasing age and was prevalent among subjects with diabetes. Cessation of smoking and alcohol may reduce the risk of AMD in this population. PMID:24178404

  11. Dietary and lifestyle risk factors associated with age-related macular degeneration: a hospital based study.

    PubMed

    Nidhi, Bhatiwada; Mamatha, Bangera Sheshappa; Padmaprabhu, Chamrajnagar Anantharajiah; Pallavi, Prabhu; Vallikannan, Baskaran

    2013-12-01

    To establish the frequency, associations and risk factors for age-related macular degeneration (AMD) in hospital population of South India. In this cross-sectional hospital based study, 3549 subjects (2090 men and 1459 women) above 45 years of age were screened randomly for AMD. Participants underwent ocular evaluation and were interviewed for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire. AMD was defined according to the international classifications and grading system. Either form of AMD was detected in 77 (2.2%) participants. Of which, early and late AMD was present in 63 (1.8%) and 14 (0.4%) subjects, respectively. Binary logistic analysis showed that the incidence of AMD was significantly higher with increasing age (Odds ratio [OR] 1.17; 95% CI 1.13-1.22) and diabetes (OR 3.97; 95% CI 2.11-7.46). However, AMD was significant among heavy cigarette smokers (OR 5.58; 95% CI 0.88-7.51) and alcoholics (OR 4.85; 95% CI 2.45-12.22). Dietary lutein/zeaxanthin (L/Z) and β-carotene intake were associated (P < 0.001) with the reduction in risk for AMD, with an OR of 0.38 and 0.65, respectively. Higher dietary intake of carotenoids, especially L/Z, was associated with lower risk for AMD. Risk of AMD is higher with increasing age and was prevalent among subjects with diabetes. Cessation of smoking and alcohol may reduce the risk of AMD in this population.

  12. Increased choroidal mast cells and their degranulation in age-related macular degeneration

    PubMed Central

    Bhutto, Imran A; McLeod, D Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard A

    2016-01-01

    Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid. PMID:26931413

  13. Identification of pathogenic genes and upstream regulators in age-related macular degeneration.

    PubMed

    Zhao, Bin; Wang, Mengya; Xu, Jing; Li, Min; Yu, Yuhui

    2017-06-26

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD. To screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AMD. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs and TFs obtained by integrated analysis. From two GEO datasets obtained, we identified 1280 DEGs (730 up-regulated and 550 down-regulated genes) between AMD and normal control (NC). After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes (TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1) was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis. The dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors (c-rel and myogenin) were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.

  14. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index.

  15. New Treatment Modalities for Neovascular Age-Related Macular Degeneration.

    PubMed

    Schlottmann, Patricio G; Alezzandrini, Arturo A; Zas, Marcelo; Rodriguez, Francisco J; Luna, José D; Wu, Lihteh

    2017-09-14

    Age-related macular degeneration (AMD) is considered one of the main causes of severe vision loss in older adults. The neovascular form (nAMD) is an advanced stage, which is responsible for the most severe vision loss. Vascular endothelial growth factor (VEGF) is at present the main factor that leads to the development of a neovascular membrane and the increased leakage from the membrane to the retina. At present, anti-VEGF therapy is the only treatment that achieves vision gains in many patients and halts progression in most of them. VEGF blockade can be achieved with several molecules and various treatment regimens, which have been studied with excellent results. Unfortunately, real-world data has shown to be far less efficacious than clinical trials. This gap between clinical trials and real-world results is an unmet medical need that supports the necessity of new treatment modalities for nAMD. Of the various treatments being studied, anti-VEGFs of higher efficacy and longer durability are those more advanced in their development. Brolucizumab and abicipar pegol are 2 new anti-VEGF drugs that had positive results in phase 2 studies and are being tested in phase 3 trials at present. Other promising therapies are antiangiopoietin 2 molecules, which are in phase 2 development. At earlier stages of development but with promising results are squalamine, anti-VEGF-C and -D, and gene therapy. The future will give retina specialists a broad armamentarium with which patients may achieve high visual gains for the long term with a low treatment burden. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  16. Gene Therapy for Age-Related Macular Degeneration.

    PubMed

    Constable, Ian Jeffery; Blumenkranz, Mark Scott; Schwartz, Steven D; Barone, Sam; Lai, Chooi-May; Rakoczy, Elizabeth Piroska

    2016-01-01

    The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti-vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm; step 2 randomized an additional 3 subjects to treatment with high-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was well tolerated with a favorable safety profile in these elderly subjects with wet AMD. Subretinal injection was highly reproducible, and no drug-related adverse events were reported. Procedure-related adverse events were mild and self-resolving. Two phakic patients developed cataract and underwent cataract surgery. Four of the 6 patients responded better than the small control group in this study and historical controls in terms of maintaining vision and a relatively dry retina with zero ranibizumab retreatments per annum. Two patients required 1 ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy may prove to be a potential adjunct or alternative to conventional intravitreal injection for patients with wet AMD by providing extended delivery of a naturally occurring antiangiogenic protein.

  17. Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

    PubMed

    Martin, Daniel F; Maguire, Maureen G; Ying, Gui-shuang; Grunwald, Juan E; Fine, Stuart L; Jaffe, Glenn J

    2011-05-19

    Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further

  18. Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents.

    PubMed

    Gemenetzi, M; Lotery, A J; Patel, P J

    2017-01-01

    Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet age-related macular degeneration (AMD). However, there are emerging signals that anti-VEGF treatment can potentially increase development of geographic atrophy (GA). Histopathologic, animal, and clinical studies support this hypothesis although direct proof of a relationship between GA and use of anti-VEGF agents in neovascular AMD is not yet established. This review presents current evidence supporting an association between anti-VEGF therapy and progression of geographic atrophy. The need of exploring alternative methods of treating AMD is indirectly but clearly emphasized.

  19. Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

    PubMed

    Akuffo, Kwadwo Owusu; Beatty, Stephen; Stack, Jim; Peto, Tunde; Leung, Irene; Corcoran, Laura; Power, Rebecca; Nolan, John M

    2015-12-01

    We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

  20. Local configuration pattern features for age-related macular degeneration characterization and classification.

    PubMed

    Mookiah, Muthu Rama Krishnan; Acharya, U Rajendra; Fujita, Hamido; Koh, Joel E W; Tan, Jen Hong; Noronha, Kevin; Bhandary, Sulatha V; Chua, Chua Kuang; Lim, Choo Min; Laude, Augustinus; Tong, Louis

    2015-08-01

    Age-related Macular Degeneration (AMD) is an irreversible and chronic medical condition characterized by drusen, Choroidal Neovascularization (CNV) and Geographic Atrophy (GA). AMD is one of the major causes of visual loss among elderly people. It is caused by the degeneration of cells in the macula which is responsible for central vision. AMD can be dry or wet type, however dry AMD is most common. It is classified into early, intermediate and late AMD. The early detection and treatment may help one to stop the progression of the disease. Automated AMD diagnosis may reduce the screening time of the clinicians. In this work, we have introduced LCP to characterize normal and AMD classes using fundus images. Linear Configuration Coefficients (CC) and Pattern Occurrence (PO) features are extracted from fundus images. These extracted features are ranked using p-value of the t-test and fed to various supervised classifiers viz. Decision Tree (DT), Nearest Neighbour (k-NN), Naive Bayes (NB), Probabilistic Neural Network (PNN) and Support Vector Machine (SVM) to classify normal and AMD classes. The performance of the system is evaluated using both private (Kasturba Medical Hospital, Manipal, India) and public domain datasets viz. Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) using ten-fold cross validation. The proposed approach yielded best performance with a highest average accuracy of 97.78%, sensitivity of 98.00% and specificity of 97.50% for STARE dataset using 22 significant features. Hence, this system can be used as an aiding tool to the clinicians during mass eye screening programs to diagnose AMD.

  1. Lactation, female hormones and age-related macular degeneration: the Tromsø Study.

    PubMed

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde; Sjølie, Anne K; Lindekleiv, Haakon; Njølstad, Inger

    2013-08-01

    Some risk factors for age-related macular degeneration (AMD) have been shown to act differently in women and men. The present study aims to investigate this disparity by examining associations between female hormones, reproductive history and AMD. Women aged 65-87 years were invited to this cross-sectional, population-based study in Norway. Participants underwent physical examination, retinal photography, answered questionnaires and had blood samples taken. The sample included 1512 women, of whom 48 (3.2%) had late AMD and 378 (25%) had large drusen >125 μm phenotype. Length of breast feeding per child was significantly associated with late AMD (OR per month 0.80, 95% CI 0.68 to 0.94) in multivariable regression analysis. We observed no associations between late AMD or drusen >125 μm and contraceptives, oral hormonal replacement therapy, parity, age at first childbirth, age of menarche, age of menopause, number of menstruating years or the reason for menopause. Longer duration of lactation was associated with lower frequency of maternal late AMD when controlled for confounders. Other reproductive factors and hormone replacement therapy were not significantly associated with AMD.

  2. Prevalence of age-related macular degeneration in the US population.

    PubMed

    Klein, Ronald; Chou, Chiu-Fang; Klein, Barbara E K; Zhang, Xinzhi; Meuer, Stacy M; Saaddine, Jinan B

    2011-01-01

    To examine the prevalence of age-related macular degeneration (AMD) in non-Hispanic white, non-Hispanic black, Mexican American, and other racial/ethnic groups. A US nationally representative, population-based, cross-sectional study involving a total of 5553 persons aged 40 years and older from the 2005-2008 National Health and Nutrition Examination Survey. The main outcome measure was AMD determined by the grading of 45° digital images from both eyes using a standardized protocol. In the civilian, noninstitutionalized, US population aged 40 years and older, the estimated prevalence of any AMD was 6.5% (95% confidence interval, 5.5-7.6) and the estimated prevalence of late AMD was 0.8% (95% confidence interval, 0.5-1.3). Non-Hispanic black persons aged 60 years and older had a statistically significantly lower prevalence of any AMD than non-Hispanic white persons aged 60 years and older (odds ratio = 0.37; 95% confidence interval, 0.21-0.67). Overall, the prevalence of any AMD in the 2005-2008 National Health and Nutrition Examination Survey was 6.5%, which is lower than the 9.4% prevalence reported in the 1988-1994 Third National Health and Nutrition Examination Survey. While this finding might be explained in part by possible methodological differences, these estimates are consistent with a decreasing incidence of AMD and suggest important public health care implications.

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

    PubMed Central

    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

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

    PubMed

    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.

  5. PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration.

    PubMed

    Choudhary, Mayur; Ding, Jin-Dong; Qi, Xiaoping; Boulton, Michael E; Yao, Pei-Li; Peters, Jeffrey M; Malek, Goldis

    2016-09-08

    Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a nuclear receptor that regulates differentiation, inflammation, lipid metabolism, extracellular matrix remodeling, and angiogenesis in multiple tissues. These pathways are also central to the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss globally. With the goal of identifying signaling pathways that may be important in the development of AMD, we investigated the impact of PPARβ/δ activation on ocular tissues affected in the disease. PPARβ/δ is expressed and can be activated in AMD vulnerable cells, including retinal pigment epithelial (RPE) and choroidal endothelial cells. Further, PPARβ/δ knockdown modulates AMD-related pathways selectively. Specifically, genetic ablation of Pparβ/δ in aged mice resulted in exacerbation of several phenotypic features of early dry AMD, but attenuation of experimentally induced choroidal neovascular (CNV) lesions. Antagonizing PPARβ/δ in both in vitro angiogenesis assays and in the in vivo experimentally induced CNV model, inhibited angiogenesis and angiogenic pathways, while ligand activation of PPARβ/δ, in vitro, decreased RPE lipid accumulation, characteristic of dry AMD. This study demonstrates for the first time, selective regulation of a nuclear receptor in the eye and establishes that selective targeting of PPARβ/δ may be a suitable strategy for treatment of different clinical sub-types of AMD.

  6. Stem cell therapies for age-related macular degeneration: the past, present, and future

    PubMed Central

    Dang, Yalong; Zhang, Chun; Zhu, Yu

    2015-01-01

    In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed. PMID:25609937

  7. Plasma metabolomic study in Chinese patients with wet age-related macular degeneration.

    PubMed

    Luo, Dan; Deng, Tingting; Yuan, Wei; Deng, Hui; Jin, Ming

    2017-09-06

    Age-related macular degeneration (AMD) is a leading disease associated with blindness. It has a high incidence and complex pathogenesis. We aimed to study the metabolomic characteristics in Chinese patients with wet AMD by analyzing the morning plasma of 20 healthy controls and 20 wet AMD patients for metabolic differences. We used ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry for this analysis. The relationship of these differences with AMD pathophysiology was also assessed. Remaining data were normalized using Pareto scaling, and then valid data were handled using multivariate data analysis with MetaboAnalysis software, including unsupervised principal component analysis and supervised partial least squares-discriminate analysis. The purpose of the present work was to identify significant metabolites for the analyses. Hierarchical clustering was conducted to identify metabolites that differed between the two groups. Significant metabolites were then identified using the established database, and features were mapped on the Kyoto Encyclopedia of Genes and Genomes. A total of 5443 ion peaks were detected, all of them attributable to the same 10 metabolites. These included some amino acids, isomaltose, hydrocortisone, and biliverdin. The heights of these peaks differed significantly between the two groups. The biosynthesis of amino acids pathways also differed profoundly between patients with wet AMD and controls. These findings suggested that metabolic profiles and and pathways differed between wet AMD and controls and may provide promising new targets for AMD-directed therapeutics and diagnostics.

  8. PPARγ agonists: Potential treatments for exudative age-related macular degeneration.

    PubMed

    Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

    2017-11-01

    Choroidal neovascularization (CNV) characterizes the progression of exudative age-related macular degeneration (AMD) with the deterioration in the central vision. Vascular inflammation, and overproduction of inflammatory cytokines, growth factors and aberrant endothelial cell migration, initiate defective blood vessel proliferation in exudative AMD. CNV formation is initiated by the interplay between inflammation, the hallmark of exudative AMD, and the activation of WNT/β-catenin pathway. Upregulation of WNT/β-catenin pathway involves activation of PI3K/Akt pathway and then the Warburg effect to produce lactate. Lactate production generates VEGF expression and then participates to the initiation of CNV in exudative AMD. WNT/β-catenin pathway and PPARγ act in an opposite manner in several diseases. We focus this review on the interplay between PPARγ and canonical WNT/β-catenin pathway and the anti-inflammatory role of PPARγ in exudative AMD. In exudative AMD, PPARγ agonists downregulate inflammation and the WNT/β-catenin pathway. PPARγ agonists can appear as promising treatment against the initiation and the progression of CNV in exudative AMD. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26255974

  10. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration

    PubMed Central

    Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H.; Shaw, Peter X.; Karin, Michael; Zhang, Kang

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD. PMID:23341606

  11. PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration

    PubMed Central

    Choudhary, Mayur; Ding, Jin-dong; Qi, Xiaoping; Boulton, Michael E.; Yao, Pei-Li; Peters, Jeffrey M.; Malek, Goldis

    2016-01-01

    Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a nuclear receptor that regulates differentiation, inflammation, lipid metabolism, extracellular matrix remodeling, and angiogenesis in multiple tissues. These pathways are also central to the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss globally. With the goal of identifying signaling pathways that may be important in the development of AMD, we investigated the impact of PPARβ/δ activation on ocular tissues affected in the disease. PPARβ/δ is expressed and can be activated in AMD vulnerable cells, including retinal pigment epithelial (RPE) and choroidal endothelial cells. Further, PPARβ/δ knockdown modulates AMD-related pathways selectively. Specifically, genetic ablation of Pparβ/δ in aged mice resulted in exacerbation of several phenotypic features of early dry AMD, but attenuation of experimentally induced choroidal neovascular (CNV) lesions. Antagonizing PPARβ/δ in both in vitro angiogenesis assays and in the in vivo experimentally induced CNV model, inhibited angiogenesis and angiogenic pathways, while ligand activation of PPARβ/δ, in vitro, decreased RPE lipid accumulation, characteristic of dry AMD. This study demonstrates for the first time, selective regulation of a nuclear receptor in the eye and establishes that selective targeting of PPARβ/δ may be a suitable strategy for treatment of different clinical sub-types of AMD. PMID:27622388

  12. Pathway activation profiling reveals new insights into age-related macular degeneration and provides avenues for therapeutic interventions.

    PubMed

    Makarev, Evgeny; Cantor, Charles; Zhavoronkov, Alex; Buzdin, Anton; Aliper, Alexander; Csoka, Anotonei Benjamin

    2014-12-01

    Age-related macular degeneration (AMD) is a major cause of blindness in older people and is caused by loss of the central region of the retinal pigment epithelium (RPE). Conventional methods of gene expression analysis have yielded important insights into AMD pathogenesis, but the precise molecular pathway alterations are still poorly understood. Therefore we developed a new software program, "AMD Medicine", and discovered differential pathway activation profiles in samples of human RPE/choroid from AMD patients and controls. We identified 29 pathways in RPE-choroid AMD phenotypes: 27 pathways were activated in AMD compared to controls, and 2 pathways were activated in controls compared to AMD. In AMD, we identified a graded activation of pathways related to wound response, complement cascade, and cell survival. Also, there was downregulation of two pathways responsible for apoptosis. Furthermore, significant activation of pro-mitotic pathways is consistent with dedifferentiation and cell proliferation events, which occur early in the pathogenesis of AMD. Significantly, we discovered new global pathway activation signatures of AMD involved in the cell-based inflammatory response: IL-2, STAT3, and ERK. The ultimate aim of our research is to achieve a better understanding of signaling pathways involved in AMD pathology, which will eventually lead to better treatments.

  13. Scotopic Microperimetry in the Early Diagnosis of Age-Related Macular Degeneration: Preliminary Study

    PubMed Central

    Pescosolido, Nicola

    2014-01-01

    Background. Recent clinical studies have shown that, in some degenerative retinal diseases, like age-related macular degeneration (AMD), the sensitivity of the rods decreases more rapidly than the sensitivity of the cones. The aim of this study was to evaluate if there is a correlation between the presence of hard drusen at the macular level and the rod damage responsible for the reduction in scotopic retinal sensitivity in subjects at risk for AMD. Methods. The authors selected 24 subjects (14 men and 10 women) with an average age of 67.25 ± 5.7 years. Macular hard drusen were present in 50% of the subjects at the fundus oculi exam. The researchers evaluated the retinal sensitivity to light in mesopic and scotopic conditions of each subject with an MP-1 scotopic microperimeter (MP-1S). Results. In subjects with hard drusen in the fundus oculi examination, there was a statistically significant reduction in scotopic retinal sensitivity, while the mesopic retinal sensitivity was not compromised. Conclusion. This study revealed how the presence of hard drusen at the macular level is associated with a reduction in scotopic retinal sensitivity compared to a control group of healthy subjects. Retinal functionality in a scotopic setting examined with MP-1S could be useful in early diagnosis of AMD. PMID:25548774

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

    PubMed

    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

    2017-07-14

    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

  15. Inflammation and its role in age-related macular degeneration.

    PubMed

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.

  16. Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration.

    PubMed

    Agosta, Elisa; Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Di Desidero, Teresa; Sartini, Maria Sole; Nardi, Marco; Danesi, Romano; Bocci, Guido

    2012-07-01

    Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.

  17. Patient-reported utilities in bilateral visual impairment from amblyopia and age-related macular degeneration.

    PubMed

    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

  18. Visible light and risk of age-related macular degeneration.

    PubMed Central

    Taylor, H R; Muñoz, B; West, S; Bressler, N M; Bressler, S B; Rosenthal, F S

    1990-01-01

    Sunlight exposure has been suggested as a cause of AMD. To examine this, we collected detailed histories of ocular sun exposure in 838 watermen who work on the Chesapeake Bay. The presence and severity of AMD was assessed in stereo macular photographs. Macular changes were classified into four grades of increasing severity ranging from the presence of 5 or more drusen (AMD-1) to extensive geographic atrophy or disciform scars (AMD-4). Previously, we found no association between AMD and ocular exposure to either UV-B (290 to 320 nm) or two bands of UV-A (320 to 340 nm and 340 to 400 nm). We have undertaken further analysis to determine whether ocular exposure to violet light (400 to 450 nm), blue light (400 to 500 nm), or all visible light (400 to 700 nm) was associated with AMD. Ocular exposure was estimated using model computations of ambient irradiance and estimates of the ratio of ocular to ambient exposure. Compared to age-matched controls, established cases (AMD-4), but not milder cases, had significantly higher exposure to both blue and visible light over the preceding 20 years (Wilcoxon sign rank test, P = 0.027). There was no difference in exposure at younger ages. These data suggest that high levels of exposure to blue and visible light late in life may be important in causing AMD. PMID:2095019

  19. Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration

    PubMed Central

    Fang, Amy M.; Lee, Aaron Y.; Kulkarni, Mukti; Osborn, Melissa P.

    2009-01-01

    Purpose Genetic factors influence an individual’s risk for developing neovascular age-related macular degeneration (AMD), a leading cause of irreversible blindness. Previous studies on the potential genetic link between AMD and vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and vascular permeability, have yielded conflicting results. In the present case-control association study, we aimed to determine whether VEGF or its main receptor tyrosine kinase VEGFR-2 is genetically associated with neovascular AMD. Methods A total of 515 Caucasian patients with neovascular AMD and 253 ethically-matched controls were genotyped for polymorphisms in the VEGFA and VEGFR-2 genes. A tagging single nucleotide polymorphism (tSNP) approach was employed to cover each gene plus two kilobases on each side, spanning the promoter and 3′ untranslated regions. SNPs with a minimum allele frequency of 10% were covered by seven tSNPs in VEGFA and 20 tSNPs in VEGFR-2. Two VEGFA SNPs previously linked with AMD, rs1413711 and rs3025039, were also analyzed. Results The 29 VEGFA and VEGFR-2 SNPs analyzed in our cohort demonstrated no significant association with neovascular AMD. A single rare haplotype in the VEGFR-2 gene was associated with the presence of neovascular AMD (p=0.034). Conclusions This study is the first to investigate the association of VEGFR-2 polymorphisms with AMD and evaluates VEGFA genetic variants in the largest neovascular AMD cohort to date. Despite the angiogenic and permeability-enhancing effects of VEGF/VEGFR-2 signaling, we found minimal evidence of a significant link between polymorphisms in the VEGFA and VEGFR-2 genes and neovascular AMD. PMID:20019880

  20. Clinical characteristics of exudative age-related macular degeneration in Japanese patients.

    PubMed

    Maruko, Ichiro; Iida, Tomohiro; Saito, Masaaki; Nagayama, Dai; Saito, Kuniharu

    2007-07-01

    To clarify the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients. Retrospective, observational, consecutive case series. Two hundred and eighty-nine patients with neovascular AMD were examined. The authors classified the patients into three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. One hundred and fifty-eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%) with typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), one eye had PCV and the other eye had typical AMD. Most patients with PCV and typical AMD had unilateral disease (81.6% and 94.1%, respectively) with a male preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3 years for women) than patients with other subtypes. Serous and hemorrhagic pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22 patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the patients with unilateral disease in each subtype, large drusen in the unaffected eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP. Neovascular AMD in Japanese patients has different demographic features compared with that in White patients. In Japanese patients, there is a preponderance of PCV, male gender, unilaterality, and absence of drusen in the second eye, with the exception of RAP.

  1. Residual abilities in age-related macular degeneration to process spatial frequencies during natural scene categorization.

    PubMed

    Musel, Benoit; Hera, Ruxandra; Chokron, Sylvie; Alleysson, David; Chiquet, Christophe; Romanet, Jean-Paul; Guyader, Nathalie; Peyrin, Carole

    2011-11-01

    Age-related macular degeneration (AMD) is characterized by a central vision loss. We explored the relationship between the retinal lesions in AMD patients and the processing of spatial frequencies in natural scene categorization. Since the lesion on the retina is central, we expected preservation of low spatial frequency (LSF) processing and the impairment of high spatial frequency (HSF) processing. We conducted two experiments that differed in the set of scene stimuli used and their exposure duration. Twelve AMD patients and 12 healthy age-matched participants in Experiment 1 and 10 different AMD patients and 10 healthy age-matched participants in Experiment 2 performed categorization tasks of natural scenes (Indoors vs. Outdoors) filtered in LSF and HSF. Experiment 1 revealed that AMD patients made more no-responses to categorize HSF than LSF scenes, irrespective of the scene category. In addition, AMD patients had longer reaction times to categorize HSF than LSF scenes only for indoors. Healthy participants' performance was not differentially affected by spatial frequency content of the scenes. In Experiment 2, AMD patients demonstrated the same pattern of errors as in Experiment 1. Furthermore, AMD patients had longer reaction times to categorize HSF than LSF scenes, irrespective of the scene category. Again, spatial frequency processing was equivalent for healthy participants. The present findings point to a specific deficit in the processing of HSF information contained in photographs of natural scenes in AMD patients. The processing of LSF information is relatively preserved. Moreover, the fact that the deficit is more important when categorizing HSF indoors, may lead to new perspectives for rehabilitation procedures in AMD.

  2. Geo-Epidemiology of Age-Related Macular Degeneration: New Clues Into the Pathogenesis.

    PubMed

    Reibaldi, Michele; Longo, Antonio; Pulvirenti, Alfredo; Avitabile, Teresio; Russo, Andrea; Cillino, Salvatore; Mariotti, Cesare; Casuccio, Alessandra

    2016-01-01

    To evaluate the demographic, geographic, and race-related variables that account for geographic variability in prevalence rates of age-related macular degeneration (AMD). Systematic review, meta-regression, and decision-tree analysis. A systematic literature review of PubMed, Medline, Web of Science, and Embase databases identified population-based studies on the prevalence of AMD published before May 2014. Only population-based studies that took place in a spatially explicit geographic area that could be geolocalized, and used retinal photographs and standardized grading classifications, were included. Latitude and longitude data (geolocalization) and the mean annual insolation for the area where survey took place were obtained. Age-standardized prevalence rates across studies were estimated using the direct standardization method. Correlations between the prevalence of AMD and longitude and latitude were obtained by regression analysis. A hierarchical Bayesian meta-regression approach was used to assess the association between the prevalence of AMD and other relevant factors. We further investigated the interplay between location and these factors on the prevalence of AMD using regression based on conditional-inference decision trees. We observed significant inverse correlations between latitude or longitude, and crude or age-standardized prevalence rates, of early and late AMD (P < .001). Metaregression analysis showed that insolation, latitude, longitude, age, and race have a significant effect on the prevalence rates of early and late AMD (P < .001). Decision-tree analysis identified that the most important predictive variable was race for early AMD (P = .002) and insolation for late AMD (P = .001). Geographic position and insolation are key factors in the prevalence of AMD. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Interaction of Complement Factor H and Fibulin3 in Age-Related Macular Degeneration

    PubMed Central

    Wyatt, M. Keith; Tsai, Jen-Yue; Mishra, Sanghamitra; Campos, Maria; Jaworski, Cynthia; Fariss, Robert N.; Bernstein, Steven L.; Wistow, Graeme

    2013-01-01

    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. PMID:23840815

  5. Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.

    PubMed

    Pujol-Lereis, Luciana M; Schäfer, Nicole; Kuhn, Laura B; Rohrer, Bärbel; Pauly, Diana

    2016-01-01

    Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factor-oxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood. Recent studies, integrating results on oxidative stress, complement activation, epidemiology and ocular pathology suggested the following sequence in AMD-etiology: initially, chronic oxidative stress results in modification of proteins and lipids in the posterior of the eye; these tissue alterations trigger chronic inflammation, involving the complement system; and finally, invasive immune cells facilitate pathology in the retina. Here, we summarize the results for animal studies which aim to elucidate this molecular interplay of oxidative events and tissue-specific complement activation in the eye.

  6. Unfolding the Therapeutic Potential of Chemical Chaperones for Age-related Macular Degeneration

    PubMed Central

    Sauer, Theodor; Patel, Mrinali; Chan, Chi-Chao; Tuo, Jingsheng

    2008-01-01

    SUMMARY Recent studies suggest that pathological processes involved in age-related macular degeneration (AMD) might induce endoplasmic reticulum (ER) stress. Growing evidence demonstrates the ability of chemical chaperones to decrease ER stress and ameliorate ER stress-related disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for AMD. In this review, we examine the evidence suggesting a role for ER stress in AMD. Furthermore, we discuss the use of chaperone therapy for the treatment of ER stress-associated diseases, including other neurodegenerative diseases and retinopathies. Finally, we examine strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human disease. PMID:18528533

  7. Molecular mechanisms of subretinal fibrosis in age-related macular degeneration

    PubMed Central

    Ishikawa, Keijiro; Kannan, Ram; Hinton, David R

    2015-01-01

    Subretinal fibrosis is a result of a wound healing response that follows choroidal neovascularization in neovascular age-related macular degeneration (nAMD). Although anti-vascular endothelial growth factor therapy has become a standard treatment that improves visual acuity in many nAMD patients, unsuccessful treatment outcomes have often been attributed to the progression of subretinal fibrosis. In this review, we summarize the cellular and extracellular components of subretinal fibrous membranes and also discuss the possible molecular mechanisms including the functional involvement of growth factors and the inflammatory response in the process. Moreover, we present an murine animal model of subretinal fibrosis that might facilitate greater understanding of the pathophysiology and the development of novel therapeutic strategies for the inhibition of subretinal fibrosis in nAMD. PMID:25773985

  8. The role of the ERG in the diagnosis and treatment of Age-Related Macular Degeneration.

    PubMed

    Gerth, Christina

    2009-02-01

    Age-related macular degeneration (AMD) is affecting an increasing number of people, with 2.95 million people estimated to be affected in the USA by 2020. Possible preventive agents, such as vitamins and supplements have been studied and new treatment options for AMD have been developed in recent years. What role does electrophysiology play as a sensitive outcome measure? The most commonly used tests are the full-field electroretinogram (ffERG) and the multifocal ERG (mfERG). Test results from patients with AMD and reduced central vision need special attention in respect to fixation pattern, age-matched control data, and retinal luminance. Advantages, disadvantages and limitations of techniques will be considered, together with a review of published studies.

  9. Advanced imaging for the diagnosis of age-related macular degeneration: a case vignettes study.

    PubMed

    Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

    2017-10-09

    The aim of this study is to evaluate the diagnosis, staging, imaging and management preferences, and the effect of advanced imaging among practising optometrists in age-related macular degeneration (AMD). Up to 20 case vignettes (computer-based case simulations) were completed online in a computer laboratory in random order by 81 practising optometrists of Australia. Each case presented findings from a randomly selected patient seen previously at the Centre for Eye Health for a macular assessment in the following order: case history, preliminary tests and colour fundus photography. Participants were prompted to provide their diagnosis, management and imaging preference. One additional imaging result (either modified fundus photographs and infrared images, fundus autofluorescence, or optical coherence tomography [OCT]) was then provided and the questions repeated. Finally, all imaging results were provided and the questions repeated a third time. A total of 1,436 responses were analysed. The presence of macular pathology in AMD was accurately detected in 94 per cent of instances. The overall diagnostic accuracy of AMD was 61 per cent using colour fundus photography. This improved by one per cent using one additional imaging modality and a further four per cent using all imaging. Across all responses, a greater improvement in the diagnostic accuracy of AMD occurred following the presentation of OCT findings (versus other modalities). OCT was the most preferred imaging modality for AMD, while multimodal imaging was of greatest benefit in cases more often misdiagnosed using colour fundus photography alone. Overall, the cohort also displayed a tendency to underestimate disease severity. Despite reports that imaging technologies improve the stratification of AMD, our findings suggest that this effect may be small when applied among practising optometrists without additional or specific training. © 2017 The Authors. Clinical and Experimental Optometry published by John

  10. Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis.

    PubMed

    Pinna, Antonio; Zaccheddu, Francesco; Boscia, Francesco; Carru, Ciriaco; Solinas, Giuliana

    2016-12-14

    There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta-analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random-effects model. Twelve case-control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 μmol/l (95% confidence interval [CI] = 0.96-1.25) greater in wet AMD cases, but there was evidence of extreme between-study heterogeneity (p < 0.001, I(2)  = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 μmol/l (95% CI = 0.35-0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I(2)  = 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between-study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn.

  11. Elevated High-Density Lipoprotein Cholesterol and Age-Related Macular Degeneration: The Alienor Study

    PubMed Central

    Cougnard-Grégoire, Audrey; Delyfer, Marie-Noëlle; Korobelnik, Jean-François; Rougier, Marie-Bénédicte; Le Goff, Mélanie; Dartigues, Jean-François; Barberger-Gateau, Pascale; Delcourt, Cécile

    2014-01-01

    Background Lipid metabolism and particularly high-density lipoprotein (HDL) 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 plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. Methods The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France). AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes); large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247); late AMD (n = 40, 61). Associations of AMD with plasma lipids (HDL, total cholesterol (TC), Low-density lipoprotein (LDL), and triglycerides (TG)) were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. Results After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261), higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54–3.90; P = 0.0002) and any AMD (OR = 2.29, 95%CI: 1.46–3.59; P = 0.0003). Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48–5.17; p = 0.45). No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. Conclusions This study suggests that

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

    PubMed Central

    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

  13. Pesticide Use and Age-Related Macular Degeneration in the Agricultural Health Study.

    PubMed

    Montgomery, Martha P; Postel, Eric; Umbach, David M; Richards, Marie; Watson, Mary; Blair, Aaron; Chen, Honglei; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

    2017-07-19

    Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Few studies have investigated its relationship to environmental neurotoxicants. In previous cross-sectional studies, we found an association between pesticide use and self-reported retinal degeneration. We evaluated the association of pesticide use with physician-confirmed incident AMD. The Agricultural Health Study (AHS) is a prospective cohort of pesticide applicators and their spouses enrolled from 1993-1997 in Iowa and North Carolina. Cohort members reported lifetime use of 50 specific pesticides at enrollment. Self-reports of incident AMD during follow-up through 2007 were confirmed by reports from participants' physicians and by independent evaluation of retinal photographs provided by the physicians. Confirmed cases (n=161) were compared with AHS cohort members without AMD (n=39,108). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression with adjustment for age, gender, and smoking. AMD was associated with ever use of organochlorine [OR=2.7 (95% CI: 1.8, 4.0)] and organophosphate [OR=2.0 (95% CI: 1.3, 3.0)] insecticides and phenoxyacetate herbicides [OR=1.9 (95% CI: 1.2, 2.8)]. Specific pesticides consistently associated with AMD included chlordane, dichlorodiphenyltrichloroethane (DDT), malathion, and captan; others with notable but slightly less consistent associations were heptachlor, diazinon, phorate, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,4-dichlorophenoxyacetic acid (2,4-D). Results were similar for men and women. Some specific pesticides were associated with both early- and late-stage AMD, but others were associated with only one stage. Exposures to specific pesticides may be modifiable risk factors for AMD. https://doi.org/10.1289/EHP793.

  14. Genome-wide association studies: getting to pathogenesis, the role of inflammation/complement in age-related macular degeneration.

    PubMed

    Cooke Bailey, Jessica N; Pericak-Vance, Margaret A; Haines, Jonathan L

    2014-09-11

    Age-related macular degeneration (AMD) is a chronic, degenerative, and significant cause of visual impairment and blindness in the elderly. Genetic and epidemiological studies have confirmed that AMD has a strong genetic component, which has encouraged the application of increasingly sophisticated genetic techniques to uncover the important underlying genetic variants. Although various genes and pathways have been implicated in the risk for AMD, complement activation has been emphasized repeatedly throughout the literature as having a major role both physiologically and genetically in susceptibility to and pathogenesis of this disease. This article explores the research efforts that brought about the discovery and characterization of the role of inflammatory and immune processes (specifically complement) in AMD. The focus herein is on the genetic evidence for the role of complement in AMD as supported specifically by genome-wide association (GWA) studies, which interrogate hundreds of thousands of variants across the genome in a hypothesis-free approach, and other genetic interrogation methods.

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

    PubMed Central

    Peponis, Vasileios; Chalkiadakis, Spyridon E; Bonovas, Stefanos; Sitaras, Nikolaos M

    2010-01-01

    Objective: 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. PMID:20714364

  16. Structural and molecular changes in the aging choroid: implications for age-related macular degeneration.

    PubMed

    Chirco, K R; Sohn, E H; Stone, E M; Tucker, B A; Mullins, R F

    2017-01-01

    Age-related macular degeneration (AMD) is a devastating disease-causing vision loss in millions of people around the world. In advanced stages of disease, death of photoreceptor cells, retinal pigment epithelial cells, and choroidal endothelial cells (CECs) are common. Loss of endothelial cells of the choriocapillaris is one of the earliest detectable events in AMD, and, because the outer retina relies on the choriocapillaris for metabolic support, this loss may be the trigger for progression to more advanced stages. Here we highlight evidence for loss of CECs, including changes to vascular density within the choriocapillaris, altered abundance of CEC markers, and changes to overall thickness of the choroid. Furthermore, we review the key components and functions of the choroid, as well as Bruch's membrane, both of which are vital for healthy vision. We discuss changes to the structure and molecular composition of these tissues, many of which develop with age and may contribute to AMD pathogenesis. For example, a crucial event that occurs in the aging choriocapillaris is accumulation of the membrane attack complex, which may result in complement-mediated CEC lysis, and may be a primary cause for AMD-associated choriocapillaris degeneration. The actions of elevated monomeric C-reactive protein in the choriocapillaris in at-risk individuals may also contribute to the inflammatory environment in the choroid and promote disease progression. Finally, we discuss the progress that has been made in the development of AMD therapies, with a focus on cell replacement.

  17. The potential role of amyloid β in the pathogenesis of age-related macular degeneration

    PubMed Central

    Yoshida, Takeshi; Ohno-Matsui, Kyoko; Ichinose, Shizuko; Sato, Tetsuji; Iwata, Nobuhisa; Saido, Takaomi C.; Hisatomi, Toshio; Mochizuki, Manabu; Morita, Ikuo

    2005-01-01

    Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid β (Aβ) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Aβ on cultured human RPE cells as well as ocular findings in neprilysin gene–disrupted mice, which leads to an increased deposition Aβ. The results showed that Aβ treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Aβ-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene–disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Aβ accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Aβ reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD. PMID:16167083

  18. The Potential Importance of Detection of Neovascular Age-Related Macular Degeneration When Visual Acuity Is Relatively Good.

    PubMed

    Ho, Allen C; Albini, Thomas A; Brown, David M; Boyer, David S; Regillo, Carl D; Heier, Jeffrey S

    2017-03-01

    The advent of anti-vascular endothelial growth factor treatment has changed the prognosis for patients with neovascular age-related macular degeneration (nvAMD). The ability to stabilize or improve vision with these treatments is a major step in enabling patients to continue to function at the highest possible level. Many studies have demonstrated that the better the visual acuity (VA) is at the time of treatment initiation, the higher the likelihood that VA will be better during at least the following 2 years; as such, detection of nvAMD when VA is relatively good is important. Data on the VA of patients with intermediate AMD and VA at the time of nvAMD diagnosis suggest that patients are typically losing an average of 3 to 5 lines of vision and possibly more between the time that intermediate AMD progresses to nvAMD and the diagnosis of nvAMD is made. The average patient may have nvAMD for 6 to 12 months before diagnosis and treatment initiation. Current efforts in management of nvAMD are primarily aimed at optimizing anti-vascular endothelial growth factor treatments that have the potential to improve VA outcomes by a magnitude of letters. Additional tools or other efforts to identify patients with nvAMD before substantial vision loss has occurred may reduce the amount of visual loss sustained with anti-vascular endothelial growth factor therapy, and have the potential to improve VA outcomes substantially.

  19. Systemic, Ocular and Genetic Risk Factors for Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Singaporeans

    PubMed Central

    Cheung, Chui Ming Gemmy; Laude, Augustinus; Yeo, Ian; Tan, Shu-Pei; Fan, Qiao; Mathur, Ranjana; Lee, Shu Yen; Chan, Choi Mun; Tan, Gavin; Lim, Tock Han; Cheng, Ching-Yu; Wong, Tien Yin

    2017-01-01

    To examine the association of systemic, ocular and genetic risk factors in neovascular age-related macular degeneration (nAMD) in a large cohort of Asian patients, and to further compare risk factors between those with typical AMD and polypoidal choroidal vasculoapthy (PCV) subtypes. We recruited 456 cases and 1,824 controls matched for age, gender and ethnicity. Data on systemic and ocular risk factors were collected on questionnaires. In a subgroup of subjects, we included genetic data on four AMD-associated single nucleotide polymorphisms (SNPs). Risk factors for nAMD and subtypes were analyzed. Systemic risk factors for nAMD included older age, male gender, higher BMI and higher HDL-cholesterol. Ocular risk factors included pseudophakic and shorter axial length. Risk factors common to both typical AMD and PCV subtypes included age, BMI and HDL-cholesterol. Shorter axial length was only associated with PCV, while male gender and pseudophakia were only associated with typical AMD. In the subgroup with genotype data, ARMS2 rs10490924 and CFH rs800292 were associated with nAMD. None of the risk factors were significantly different between PCV and typical AMD. Systemic, ocular and genetic risk factors were largely similar for typical AMD and PCV subtypes in this Asian population based in Singapore. PMID:28120909

  20. [Current concepts in pathogenesis of age-related macular degeneration].

    PubMed

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

    2014-01-01

    Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

  1. Nature and nurture- genes and environment- predict onset and progression of macular degeneration.

    PubMed

    Sobrin, Lucia; Seddon, Johanna M

    2014-05-01

    Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including antioxidants and dietary fat intake influence onset and progression of AMD. There are also several lines of evidence that link cardiovascular, immune and inflammatory biomarkers to AMD. The genetic etiology of AMD has been and continues to be an intense and fruitful area of investigation. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing our knowledge of how rare genetic variants strongly impact disease. Evidence for interactions between environmental, therapeutic and genetic factors is emerging and elucidating the mechanisms of this interplay remains a major challenge in the field. Genotype-phenotype associations are evolving. The knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and our ability to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Background chromatic contrast preference in cases with age-related macular degeneration

    PubMed Central

    Alizadeh-Ebadi, Mahmoud; Markowitz, Samuel N.; Shima, Noboru

    2013-01-01

    Objective To identify background chromatic contrast preferred subjectively by patients with age-related macular degeneration (AMD). Methods Prospective observational case series. Study subjects with AMD were recruited and compared to a control group of study subjects with normal vision. Study subjects were presented with letter size printed sheets of white paper with randomly typed 2 M size standard black optotypes. Chromatic contrast was created with colored plastic sheets positioned on top of the black on white printed sheets. The 4 major color hues which were selected for testing were blue, yellow, green and red. Study subjects were required to identify background contrast best preferred for viewing at the end of 4 trial sequences. Results 40 subjects with AMD were recruited together with 57 study subjects with normal vision. In either the control group or the group with AMD subjects the majority's chromatic preference for background was yellow (56.14%, p = 0.42 and 71.67%, p = 0.006 respectively) with subjects with AMD preferring yellow color background significantly more than subjects with normal vision (p = 0.0002). Conclusions Yellow color background seems to be preferred by most of healthy and AMD eyes. This preference may be modulated by factors such as the yellow-blue vision processing channel and/or luminosity differences produced by selectively transmitted light.

  4. Endoplasmic Reticulum Stress in Age-Related Macular Degeneration: Trigger for Neovascularization

    PubMed Central

    Salminen, Antero; Kauppinen, Anu; Hyttinen, Juha MT; Toropainen, Elisa; Kaarniranta, Kai

    2010-01-01

    Age-related macular degeneration (AMD) can be classified into two main categories: the atrophic, dry form and the exudative, wet form. The crucial difference between dry and wet AMD is the development of choroidal neovascularization in wet AMD. One fundamental cause of the neovascularization is the increased expression of VEGF (vascular endothelial growth factor) in retinal pigment epithelial cells. Progression of AMD is linked to augmentation of cellular stress, for example, oxidative stress, proteotoxic stress, inflammation and hypoxia. All these conditions can trigger stress in endoplasmic reticulum (ER), which maintains protein quality control in cells. ER stress induces the unfolded protein response (UPR) via IRE1 (inositol-requiring protein-1), PERK (protein kinase RNA-like ER kinase) and ATF6 (activating transcription factor-6) transducers. UPR signaling is a double-edged sword, that is, it can restore cellular homeostasis as far as possible, but ultimately may lead to chronic, overwhelming stress that can cause apoptotic cell death. Interestingly, ER stress is a well-known inducer of angiogenesis in cancer. Moreover, stress conditions associated with the progress of AMD can induce the expression of VEGF. We discuss the role of ER stress in the regulation of neovascularization and the conversion of dry AMD to its wet, detrimental counterpart. PMID:20683548

  5. Health State Utility Values for Age-Related Macular Degeneration: Review and Advice.

    PubMed

    Butt, Thomas; Tufail, Adnan; Rubin, Gary

    2017-02-01

    Health state utility values are a major source of uncertainty in economic evaluations of interventions for age-related macular degeneration (AMD). This review identifies and critiques published utility values and methods for eliciting de novo utility values in AMD. We describe how utility values have been used in healthcare decision making and provide guidance on the choice of utility values for future economic evaluations for AMD. Literature was searched using PubMed, and health technology assessments (HTA) were searched using HTA agency websites to identify articles reporting utility values or approaches to derive utility values in AMD and articles applying utilities for use in healthcare decision making relating to treatments for AMD. A total of 70 studies qualified for data extraction, 22 of which were classified as containing utility values and/or elicitation methods, and 48 were classified as using utility values in decision making. A large number of studies have elicited utility values for AMD, although those applied to decision making have focused on a few of these. There is an appreciation of the challenges in the measurement and valuation of health states, with recent studies addressing challenges such as the insensitivity of generic health-related quality of life (HRQoL) questionnaires and utility in the worse-seeing eye. We would encourage careful consideration when choosing utility values in decision making and an explicit critique of their applicability to the decision problem.

  6. Assessment of visual distortions in age-related macular degeneration: emergence of new approaches

    PubMed Central

    Vazquez, Noelia Pitrelli; Knox, Paul C.

    2016-01-01

    Aims With the arrival of effective treatments for neovascular age-related macular degeneration (nvAMD) there is a need to find improved tests that would allow early detection. Ideally, these tests would allow monitoring of vision by patients themselves from home. The aim of this review is to discuss the available evidence for two recently developed vision tests designed for this purpose: the Preferential Hyperacuity Perimeter (PHP) test and the Radial Shape Discrimination (RSD) test. Methods Articles that investigated detection of nvAMD were reviewed. The methodology of the clinical evidence, where available, was judged for bias and applicability of the results to the general population using the QUADAS-2 quality assessment tool. Results The PHP test has proved to be good at detecting nvAMD but many studies assessed in this review were biased in the selection of patients, restricting the results to only those patients who can use the test and produce reliable results. On the other hand the RSD test is a simple test, well accepted by elderly patients with AMD. However, clinical studies to determine its value in the detection of early signs of nvAMD are still required. Conclusions To date, more studies have investigated the utility of the PHP test compared with the RSD test for detection of nvAMD. Both tests show promise but further evidence is needed to determine the real generalisability of the PHP test and the sensitivity of the RSD test. PMID:27738450

  7. Association between Blood Lead Levels and Age-Related Macular Degeneration

    PubMed Central

    Hwang, Ho Sik; Lee, Seung Bum; Jee, Donghyun

    2015-01-01

    Purpose To investigate the association between blood lead levels and prevalence of age-related macular degeneration (AMD). Methods A nationwide population-based cross-sectional study included 4,933 subjects aged over 40 years who participated in the 2008–2012 Korean National Health and Nutrition Examination Survey, and for whom fundus photographs were available. All participants underwent a standardized interview, evaluation of blood lead concentration, and a comprehensive ophthalmic examination. Digital fundus photographs (45°) were taken of both eyes under physiological mydriasis. All fundus photographs were graded using an international classification and grading system. Results Mean blood lead levels were 3.15 μg/dL in men and 2.27 μg/dL in women (P < 0.001). After adjusting for potential confounders including age, gender, smoking status, total cholesterol levels, triglyceride levels, heart problems and strokes, the adjusted odds ratio (OR) in women for any AMD was 1.86 (95% Confidence Interval [CI], 1.03–3.36) and for early AMD was 1.92 (95% CI, 1.06–3.48), for those in the highest quintile of lead level compared with the lowest quintile. In men, however, blood lead level was not significantly associated with AMD. Conclusions Blood lead levels were higher in men, but were only associated with AMD in women. Increased levels of blood lead may be involved in the pathogenesis of AMD development in women. PMID:26252225

  8. Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration

    PubMed Central

    Zinkernagel, Martin S.; Zysset-Burri, Denise C.; Keller, Irene; Berger, Lieselotte E.; Leichtle, Alexander B.; Largiadèr, Carlo R.; Fiedler, Georg M.; Wolf, Sebastian

    2017-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD, we sequenced the gut metagenomes of patients with AMD and controls. The genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum were relatively enriched in patients with AMD, whereas Bacteroides eggerthii was enriched in controls. Patient’s intestinal microbiomes were enriched in genes of the L-alanine fermentation, glutamate degradation and arginine biosynthesis pathways and decreased in genes of the fatty acid elongation pathway. These findings suggest that modifications in the intestinal microbiome are associated with AMD, inferring that this common sight threatening disease may be targeted by microbiome-altering interventions. PMID:28094305

  9. Genetic control of the alternative pathway of complement in humans and age-related macular degeneration.

    PubMed

    Hecker, Laura A; Edwards, Albert O; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H; Brown, William L; Charbel Issa, Peter; Scholl, Hendrik P; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E; Bailey, Kent R; Oppermann, Martin

    2010-01-01

    Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues.

  10. Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration

    PubMed Central

    Keles, Sadullah; Ates, Orhan; Kartal, Baki; Alp, Hamit Hakan; Ekinci, Metin; Ceylan, Erdinc; Ondas, Osman; Arpali, Eren; Dogan, Semih; Yildirim, Kenan; Keles, Mevlut Sait

    2014-01-01

    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. PMID:25210424

  11. Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration

    PubMed Central

    Brantley, Milam A.; Osborn, Melissa P.; Sanders, Barton J.; Rezaei, Kasra A.; Lu, Pengcheng; Li, Chun; Milne, Ginger L.; Cai, Jiyang; Sternberg, Paul

    2011-01-01

    Purpose To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes. Design Prospective case-control study Methods Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were measured, and participants were genotyped for polymorphisms in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes. Results CySS was elevated in cases compared to controls (p = 0.013). After adjustment for age, gender, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (p = 0.028) as well as an eight-allele CFH haplotype (p = 0.029) after correction for age, gender, and smoking. None of the other plasma markers was related to AMD status in our cohort. Conclusions Our investigation of the gene/environment interaction involved in AMD revealed a relationship between a plasma biomarker of oxidative stress (CySS) and CFH genotype. These data suggest a potential association between inflammatory regulators and redox status in AMD pathogenesis. PMID:22035603

  12. Plasmatic Ganglioside Profile and Age-Related Macular Degeneration: A Case-Control Study.

    PubMed

    Dossarps, Denis; Martine, Lucy; Berdeaux, Olivier; Sibille, Estelle; Bron, Alain M; Creuzot-Garcher, Catherine P; Bretillon, Lionel; Masson, Elodie A Y

    2016-01-01

    Gangliosides are glycosphingolipids that are particularly abundant in the nervous system, including the retina. However, their precise role in this tissue and its pathologies remain poorly understood. The objective of the present study was to characterize the ganglioside profile of human plasma and to determine whether it is affected in age-related macular degeneration (AMD). Eighty-three subjects were included: control subjects (n = 25), atrophic AMD patients (n = 27) and exudative AMD patients (n = 31). For each subject, gangliosides were extracted from plasma and analyzed by liquid chromatography coupled to mass spectrometry. GM3 appeared to be by far the major ganglioside of human plasma, associated with GD3. No specific ganglioside class was detected in the plasma of AMD patients. Fourteen molecular species of GM3 and 9 species of GD3, accounting for the variability of the ceramide moiety of the ganglioside molecule, were identified and characterized. Analyses revealed no significant differences in the proportion of these species between control, atrophic and exudative AMD patient groups. Total GM3 levels did not differ either. Although gangliosides are considered important for the retina's structure and function, it seems that circulating gangliosides are not associated with the retinal damage occurring during the course of AMD. © 2016 S. Karger AG, Basel.

  13. The potential preventive effects of vitamins for cataract and age-related macular degeneration.

    PubMed

    Jacques, P F

    1999-05-01

    Age-related cataract and age-related macular degeneration (AMD) are important public health problems. Approximately 50% of the 30 to 50 million cases of blindness worldwide result from unoperated cataract. In the US and other developed countries AMD is the leading cause of blindness, but age-related cataract remains the leading cause of visual disability. Age-related cataract and AMD represent an enormous economic burden. In the United States more than 1.3 million cataract extractions are performed annually at a cost of approximately $3.5 billion. Much of the experimental research on the etiology of cataract and AMD has focused on the role of nutritional antioxidants (vitamin C, vitamin E, and carotenoids). Evidence from epidemiologic studies support a role for nutritional antioxidants in delaying the onset of these age-related vision disorders. Although it is not yet possible to conclude that antioxidant nutrients have a role in prevention of cataract or AMD, a summary of the epidemiologic evidence suggests that it is prudent to consume diets high in vitamins C and E and carotenoids, particularly the xanthophylls, as insurance against the development of cataract and AMD.

  14. Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

    PubMed Central

    Phan, Thanh Vân; Seoud, Lama; Chakor, Hadi; Cheriet, Farida

    2016-01-01

    Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID:27190636

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

    PubMed

    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.

  16. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration.

    PubMed

    Cuellar-Partida, Gabriel; Craig, Jamie E; Burdon, Kathryn P; Wang, Jie Jin; Vote, Brendan J; Souzeau, Emmanuelle; McAllister, Ian L; Isaacs, Timothy; Lake, Stewart; Mackey, David A; Constable, Ian J; Mitchell, Paul; Hewitt, Alex W; MacGregor, Stuart

    2016-05-31

    Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h(2)g = 0.42 ± 0.09) and AMD (h(2)g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h(2)g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (rg = 0.47 ± 0.25) which remained after removing known loci (rg = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (rg = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors.

  17. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration

    PubMed Central

    Cuellar-Partida, Gabriel; Craig, Jamie E.; Burdon, Kathryn P.; Wang, Jie Jin; Vote, Brendan J.; Souzeau, Emmanuelle; McAllister, Ian L.; Isaacs, Timothy; Lake, Stewart; Mackey, David A.; Constable, Ian J.; Mitchell, Paul; Hewitt, Alex W.; MacGregor, Stuart

    2016-01-01

    Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h2g = 0.42 ± 0.09) and AMD (h2g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h2g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (rg = 0.47 ± 0.25) which remained after removing known loci (rg = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (rg = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors. PMID:27241461

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

    PubMed Central

    2010-01-01

    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. PMID:21144031

  19. Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration

    PubMed Central

    McLeod, D. Scott; Bhutto, Imran; Edwards, Malia M.; Silver, Rachel E.; Seddon, Johanna M.; Lutty, Gerard A.

    2016-01-01

    Purpose Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. Methods Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR–positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. Results In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. Conclusions The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease. PMID:27802514

  20. Homocysteine, folate, vitamin B-12, and 10-y incidence of age-related macular degeneration.

    PubMed

    Gopinath, Bamini; Flood, Victoria M; Rochtchina, Elena; Wang, Jie Jin; Mitchell, Paul

    2013-07-01

    Epidemiologic evidence of a relation between serum total homocysteine (tHcy), vitamin B-12, and folate and age-related macular degeneration (AMD) is inconsistent and unresolved. In this cohort study, we aimed to investigate associations between intakes and serum concentrations of folate and vitamin B-12 or serum tHcy and 10-y AMD incidence. Serum folate, vitamin B-12, and tHcy were determined from blood samples drawn in 1997-1999 from cohort members aged ≥55 y. AMD was assessed in 1760 survivors from retinal photographs taken in 2002-2004 and 2007-2009. Total intakes of folate and vitamin B-12 were assessed by using a food-frequency questionnaire. After adjustment for age, sex, current smoking, white blood cell count, and fish consumption, each 1-SD increase in serum tHcy was associated with increased risk of incident early and any AMD [ORs (95% CIs): 1.33 (1.09, 1.63) and 1.33 (1.11, 1.60), respectively]. Participants with a serum vitamin B-12 deficiency (<185 pmol/L) had higher risk of incident early and late AMD [ORs (95% CIs): 1.58 (1.06, 2.36) and 2.56 (1.38, 4.73), respectively]. Folate deficiency (<11 nmol/L) was associated with 75% and 89% increased risk of incident early and any AMD, respectively, 10 y later. Participants who reported supplementary vitamin B-12 intake had 47% reduced risk of incident any AMD (OR: 0.53; 95% CI: 0.33, 0.85). Elevated serum tHcy and folate and vitamin B-12 deficiencies predicted increased risk of incident AMD, which suggests a potential role for vitamin B-12 and folate in reducing AMD risk.

  1. Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

    PubMed

    Lee, Wan-Ju Annabelle; Cheng, Ching-Lan; Lee, Cheng-Han; Kao Yang, Yea-Huei; Lin, Swu-Jane; Hsieh, Cheng-Yang

    2017-10-01

    Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Evaluation of fundus autofluorescence patterns in age-related macular degeneration

    PubMed Central

    Venkatesh, Pradeep; Sagar, Pradeep; Chawla, Rohan; Gogia, Varun; Vohra, Rajpal; Sharma, Yog Raj

    2016-01-01

    AIM To study the various morphological patterns of fundus autofluorescence (FAF) images in patients with age-related macular degeneration (AMD) in Indian population. METHODS Totally 179 eyes of 104 patients with clinical diagnosis of AMD were recruited into the study. Autofluorescence images were captured using confocal scanning laser ophthalmoscope and the patterns of FAF were classified. RESULTS Of 179 eyes, 27 (15.08%) were early AMD, 58 (32.41%) were intermediate AMD, 94 eyes (52.51%) were late AMD. Of 94 eyes with late AMD, 79 (84.04%) were neovascular AMD and 15 (15.96%) were central geographic atrophy. In eyes with early and intermediate AMD, 9 patterns of FAF were noted. Six patterns (normal, minimal change, focal increased, patchy increased, linear, reticular) were similar to that in the published classification. Two patterns (lacelike and speckled) described in the published classification were not found. Three new patterns (focal hypo-fluorescence, patchy hypo-fluorescence, mixed focal hypo-fluorescence and hyper-fluorescence) were detected. In eyes with neovascular AMD, 6 morphological patterns of FAF were noted. Two patterns (mixed hypo-fluorescence and hyper-fluorescence, central hypo-fluorescence with hyper-fluorescent rim) were similar to that in published classification. Two patterns (normal, near normal or normal background fluorescence in the centre of hypo-fluorescent area) described in the published classification were not found. Four new patterns (minimal change, hypo-fluorescent patch, central hypo-fluorescence with surrounding reticular, bull's eye) were recognized. In eye with central geographic atrophy 5 morphological patterns were noted and these were similar to that in published classification. CONCLUSION Phenotypic differences in the pattern of FAF exist in the study population compared to existing classification systems. PMID:28003979

  3. Age-related macular degeneration--emerging pathogenetic and therapeutic concepts.

    PubMed

    Gehrs, Karen M; Anderson, Don H; Johnson, Lincoln V; Hageman, Gregory S

    2006-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene--which encodes the major inhibitor of the complement alternative pathway--is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel

  4. Diabetic retinopathy and age-related macular degeneration in the U.S.

    PubMed

    Gibson, Diane M

    2012-07-01

    Diabetic retinopathy and age-related macular degeneration (AMD) are two of the most common eye diseases in the U.S. Effective treatments exist for some stages of these conditions. This goal of this study was to examine the frequency and predictors of unawareness of diabetic retinopathy and AMD. The 2005-2008 National Health and Nutrition Examination Survey (NHANES) collected digital retinal images of survey participants aged ≥40 years that were graded for diabetic retinopathy and AMD using standard protocols. A sample of individuals with diabetic retinopathy was created, as was a separate sample of individuals with AMD. Individuals were categorized as unaware of their condition if they did not report that they had the condition. Separate logistic regression models of unawareness of diabetic retinopathy and AMD were estimated in 2011. This study estimated that 73% of individuals with diabetic retinopathy and 84% of individuals with AMD were unaware of their condition. The odds of unawareness of diabetic retinopathy were higher for individuals with less-severe diabetic retinopathy, shorter diabetes duration, smaller families, or who had not had a recent eye exam. The odds of unawareness of AMD were higher for individuals with "early" AMD or who were younger, less educated, or not primarily English speakers. The very high frequency of unawareness of diabetic retinopathy and AMD suggests that unawareness of these conditions should be a major public health concern and that efforts are needed to increase the frequency of eye exams among those at risk for these conditions. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration.

    PubMed

    McLeod, D Scott; Bhutto, Imran; Edwards, Malia M; Silver, Rachel E; Seddon, Johanna M; Lutty, Gerard A

    2016-11-01

    Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR-positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.

  6. Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration

    PubMed Central

    Meyers, Kristin J.; Liu, Zhe; Millen, Amy E.; Iyengar, Sudha K.; Blodi, Barbara A.; Johnson, Elizabeth; Snodderly, D. Max; Klein, Michael L.; Gehrs, Karen M.; Tinker, Lesley; Sarto, Gloria E.; Robinson, Jennifer; Wallace, Robert B.; Mares, Julie A.

    2015-01-01

    Purpose Healthy diets and lifestyles are thought to protect against age-related macular degeneration (AMD), but whether the benefits vary across high risk AMD genotypes is unknown. The objective is to investigate the joint effects of healthy diet and lifestyle with genetic risk on the odds for AMD. Design Healthy lifestyles scores and their interactions with AMD risk genotypes were studied in relation to the prevalence of AMD, assessed six years later. Participants Women 50–79 years of age in the Carotenoids in Age-Related Eye Disease Study (CAREDS) with exposure and AMD data available (N=1,663). Methods Healthy lifestyle scores (0–6 points) were assigned based on Healthy Eating Index scores, physical activity (MetHrs/week), and pack years of smoking assessed between 1994–1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Interactions between healthy lifestyle score and genotype in relation to the odds of AMD were assessed. Main Outcome Stereoscopic fundus photographs were taken and graded for AMD six years after exposure assessment (2001–2004). A total of 308 women had early AMD and 29 had late AMD). Results The odds of AMD were 3.3 times greater in women with both low healthy lifestyle score (0–2) and high risk CFH genotype (CC), relative to those who had low genetic risk (TT) and healthy lifestyle scores of 4–6 (95% CI:1.8–6.1). There were no significant additive (SI=1.08, 95% CI: 0.70–1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. Limiting the sample to those with stable diets prior to AMD assessment (n=728) strengthened the joint effects (OR=4.6, 95% CI: 1.85–11.6) and suggested high risk genotype and low lifestyle score combined had a stronger association than expected by simply adding the two effects (SI=1.34, 95% CI: 1.05–1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained the

  7. Dynamic soft drusen remodelling in age-related macular degeneration

    PubMed Central

    Smith, R Theodore; Sohrab, Mahsa A; Pumariega, Nicole; Chen, Yue; Chen, Jian; Lee, Noah; Laine, Andrew

    2010-01-01

    Aims To demonstrate and quantify the dynamic remodelling process of soft drusen resorption and new drusen formation in age-related macular degeneration (AMD) with novel interactive methods. Methods Twenty patients with large soft drusen bilaterally and without advanced AMD were imaged at baseline and again at a mean interval of 2 years (40 eyes, 80 images). Each of the 40 serial pairs of images was precisely registered by an automated technique. The drusen were segmented by a user-interactive method based on a background levelling algorithm and classified into three groups: new drusen (only in the final image), resorbed drusen (present initially but not in the final image) and stable drusen (present in both images). We measured each of these classes as well as the absolute change in drusen |D1 – D0| and the dynamic drusen activity (creation and resorption) Dnew+Dresorbed. Results Mean dynamic activity for the right eye (OD) was 7.33±65.50%, significantly greater than mean absolute change (2.71±2.89%, p=0.0002, t test), with similar results for the left eye (OS). However, dynamic activity OD compared with OS (mean 7.33±5.50 vs 7.91±4.16%, NS) and absolute net change OD versus OS (2.71±2.89 vs 3.46±3.97%, NS) tended to be symmetrical between fellow eyes. Conclusions Dynamic remodelling processes of drusen resorption and new drusen formation are distinct disease activities that can occur simultaneously and are not captured by change in total drusen load. Dynamic changes occur at rates more than twice that of net changes, and may be a useful marker of disease activity. PMID:20530179

  8. Residual colour detection abilities in age-related macular degeneration.

    PubMed

    Shima, Noboru; Markowitz, Samuel N; Reyes, Sophia V

    2013-08-01

    To quantify residual abilities to identify a target's colour in cases with age-related macular degeneration (AMD). Subjects with AMD with best corrected visual acuity (BCVA) of 20/50 to 20/400 in the better eye (test eye) and age older than 55 years were recruited. A separate matching control group was recruited with subjects with BCVA of 20/40 or better. Each subject was presented sequentially with square-shaped colour targets corresponding in size to optotype sizes used in standard Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocols, all against a white background. Four major colour hues were selected for testing: blue, yellow, green, and red. The same subjects were tested with standard ETDRS targets (black on white), and results served as control group references. The primary outcome measure selected for analysis was the minimum angle of resolution (MAR) required to correctly identify the hue presented. Forty study subjects (14 males and 26 females) aged 55 to 95 years (mean 79.45 years, SD 8.82) were recruited. Thirty similar subjects were recruited for a control group. Red on white estimates were better than for other colours and related best to standard black on white ETDRS estimates (20/121 vs 20/132, respectively). Also, red on white estimates seem not to be affected by age. Estimates for colour detection for the control group were not different among colours tested and were not affected by age. Ranking abilities according to the MAR required to identify a hue can serve as a quantifying measure for residual colour vision. Our findings reflect functional abilities rather than psychophysical measurements. Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  9. Investigating mitochondria as a target for treating age-related macular degeneration.

    PubMed

    Terluk, Marcia R; Kapphahn, Rebecca J; Soukup, Lauren M; Gong, Hwee; Gallardo, Christopher; Montezuma, Sandra R; Ferrington, Deborah A

    2015-05-06

    Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Although the pathological mechanisms have not been definitively elucidated, evidence suggests a key role for mitochondrial (mt) dysfunction. The current study used our unique collection of human retinal samples graded for the donor's stage of AMD to address fundamental questions about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in the diseased retina, damage in the retinal pigment epithelium (RPE) and neural retina from individual donors were compared. To directly test a long-held belief that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in the macula and peripheral sections from individual donors. Small segments of the entire mt genome were examined to determine whether specific regions are preferentially damaged. Our results show that mtDNA damage is limited to the RPE, equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of damage are localized to regions of the mt genome that may impact mt function. These results provide a scientific basis for targeting the RPE mitochondria with therapies that protect and enhance mt function as a strategy for combating AMD.

  10. A genetic approach to stratification of risk for age-related macular degeneration.

    PubMed

    Zanke, Brent; Hawken, Steven; Carter, Ronald; Chow, David

    2010-02-01

    The genetic determinants of age-related macular degeneration (AMD) are reviewed and a novel approach to risk determination based upon inherited genetic polymorphisms and smoking history is presented. Although AMD was long thought to have primarily an environmental etiology, genetic variation is now known to account for the majority of the disease risk, with variations in the genes of the complement pathways playing a prominent role. Independent and validated clinical studies have implicated the C3 gene and its regulator, complement factor H (1q31.1), complement component 2 (6q21.33), and complement factor B (6q21.33). Subtle variations in complement activity increase the risk of symptomatic macular inflammation with age. A second group of AMD-associated genetic markers may aggravate complement-mediated inflammation by permitting retinal oxidative damage. Variation within the chromosomal site (10q26) coding a mitochondrial-associated protein (age-related maculopathy susceptibility 2) and an independent variation within the mitochondrial genome itself (A4917G) suggest a contributing pathophysiological role of retinal oxidative stress. A genetic panel of disease-susceptibility markers and smoking history can identify a group of individuals with greater than 65% lifetime risk of AMD. The introduction of genetic marker testing into clinical practice may identify patients with early disease who may be aided by presymptomatic monitoring or inclusion into trials of newer prophylactic agents.

  11. Investigating Mitochondria as a Target for Treating Age-Related Macular Degeneration

    PubMed Central

    Terluk, Marcia R.; Kapphahn, Rebecca J.; Soukup, Lauren M.; Gong, Hwee; Gallardo, Christopher; Montezuma, Sandra R.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. Although the pathological mechanisms have not been definitively elucidated, evidence suggests a key role for mitochondrial (mt) dysfunction. The current study used our unique collection of human retinal samples graded for the donor's stage of AMD to address fundamental questions about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in the diseased retina, damage in the retinal pigment epithelium (RPE) and neural retina from individual donors were compared. To directly test a long-held belief that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in the macula and peripheral sections from individual donors. Small segments of the entire mt genome were examined to determine whether specific regions are preferentially damaged. Our results show that mtDNA damage is limited to the RPE, equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of damage are localized to regions of the mt genome that may impact mt function. These results provide a scientific basis for targeting the RPE mitochondria with therapies that protect and enhance mt function as a strategy for combating AMD. PMID:25948278

  12. Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration.

    PubMed

    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

  13. Peripapillary choroidal thickness in patients with early age-related macular degeneration and reticular pseudodrusen.

    PubMed

    Yun, Cheolmin; Oh, Jaeryung; Ahn, Soh-Eun; Hwang, Soon-Young; Kim, Seong-Woo; Huh, Kuhl

    2016-03-01

    The purpose of this study was to investigate peripapillary and macular choroidal thickness (CT) in patients with early age-related macular degeneration (AMD) with or without reticular pseudodrusen (RPD). We investigated the medical records of 89 patients (89 eyes) with early AMD. The eyes were grouped into three categories according to the extent of RPD: no RPD, localized RPD, and diffuse RPD. Peripapillary and macular CT were measured with images obtained by spectral domain optical coherence tomography. CT in the peripapillary and macular areas was compared among groups. Both RPD groups exhibited an older subject age and a greater female predominance compared to the non-RPD group (P = 0.007 and P = 0.030, respectively). Macular and peripapillary CT were different among the three groups (all, P < 0.001), and both RPD groups showed a thinner choroid in all areas compared to the non-RPD group after adjusting for age and sex (all, P ≤ 0.016). Temporal peripapillary and nasal macular CT at 500 μm and 1500 μm, respectively, from the fovea in eyes with diffuse RPD were significantly thinner than that in eyes with localized RPD (P = 0.008, P = 0.016 and P < 0.001, respectively). In addition to the macular area, the peripapillary CT, including the area outside the macula, was thinner in eyes with RPD than in those without RPD. Significant differences in the papillomacular choroid were observed based on RPD distribution type, which suggests that variation in CT is based on the extent of RPD.

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

    PubMed

    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

  15. APOE Isoforms Control Pathogenic Subretinal Inflammation in Age-Related Macular Degeneration.

    PubMed

    Levy, Olivier; Lavalette, Sophie; Hu, Shulong J; Housset, Michael; Raoul, William; Eandi, Chiara; Sahel, José-Alain; Sullivan, Patrick M; Guillonneau, Xavier; Sennlaub, Florian

    2015-10-07

    Contrary to Alzheimer's disease (AD), the APOE2 allele increases and the APOE4 allele reduces the risk to develop age-related macular degeneration (AMD) compared with the most common APOE3 allele. The underlying mechanism for this association with AMD and the reason for the puzzling difference with AD are unknown. We previously demonstrated that pathogenic subretinal mononuclear phagocytes (MPs) accumulate in Cx3cr1-deficient mice due to the overexpression of APOE, interleukin-6, and CC chemokine ligand 2 (CCL2). We here show using targeted replacement mice expressing the human APOE isoforms (TRE2, TRE3, and TRE4) that MPs of TRE2 mice express increased levels of APOE, interleukin-6, and CCL2 and develop subretinal MP accumulation, photoreceptor degeneration, and exaggerated choroidal neovascularization similar to AMD. Pharmacological inhibition of the cytokine induction inhibited the pathogenic subretinal inflammation. In the context of APOE-dependent subretinal inflammation in Cx3cr1(GFP/GFP) mice, the APOE4 allele led to diminished APOE and CCL2 levels and protected Cx3cr1(GFP/GFP) mice against harmful subretinal MP accumulation observed in Cx3cr1(GFP/GFP)TRE3 mice. Our study shows that pathogenic subretinal inflammation is APOE isoform-dependent and provides the rationale for the previously unexplained implication of the APOE2 isoform as a risk factor and the APOE4 isoform as a protective factor in AMD pathogenesis. The understanding of how genetic predisposing factors, which play a major role in age-related macular degeneration (AMD), participate in its pathogenesis is an important clue to decipher the pathomechanism and develop efficient therapies. In this study, we used transgenic, targeted replacement mice that carry the three human APOE isoform-defining sequences at the mouse APOE chromosomal location and express the human APOE isoforms. Our study is the first to show how APOE2 provokes and APOE4 inhibits the cardinal AMD features, inflammation

  16. Optical Coherence Tomography Angiography of Indocyanine Green Angiographic Plaques in Asymptomatic Intermediate Age-Related Macular Degeneration

    PubMed Central

    Roisman, Luiz; Zhang, Qinqin; Wang, Ruikang K.; Gregori, Giovanni; Zhang, Angi; Chen, Chieh-Li; Durbin, Mary K.; An, Lin; Stetson, Paul F.; Rosenfeld, Philip J.

    2016-01-01

    Objective To correlate images from swept source optical coherence tomography microangiography (SS-OMAG) with images from fluorescein angiography (FA) and indocyanine green angiography (ICGA) performed on asymptomatic eyes with intermediate age-related macular degeneration. Study Design and Methods A retrospective, observational, consecutive case series of patients with asymptomatic, intermediate AMD in one eye and neovascular AMD in their fellow eye. The patients underwent SS-OMAG, FA, and ICGA, and the images obtained from these three angiographic techniques were compared. Results Three patients were identified with intermediate AMD in one eye and symptomatic, neovascular AMD in their fellow eye. The three asymptomatic eyes had drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on OCT imaging. One patient presented with minimal leakage on FA from the asymptomatic eye. ICGA revealed the presence of central macular plaques, and SS-OMAG revealed type 1 neovascularization corresponding to the plaques. The type 1 neovascularization was visualized using en face slabs that extended from the border of the outer retina to the choriocapillaris (CC), 8 μm beneath Bruch’s membrane. Conclusions SS-OMAG identified type 1 neovascularization within ICGA plaques. The ability of OCTA to provide non-invasive, fast, detailed, depth-resolved identification of non-exudative neovascular lesions in eyes with intermediate AMD suggests the need for new terminology that distinguishes between non-exudative intermediate AMD and non-exudative, neovascular intermediate AMD. This distinction should prove useful for managing AMD patients at risk for conversion to late, exudative AMD once natural history studies are performed to better understand disease progression. PMID:26876696

  17. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration.

    PubMed

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie; Sagoo, Mandeep S; Tufail, Adnan; Balaggan, Kamaljit S; Patel, Praveen J

    2017-05-01

    The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration

    PubMed Central

    Rosenfeld, Philip J.

    2016-01-01

    Purpose To explain the pivotal role optical coherence tomography (OCT) imaging had in the development of antiangiogenic therapies for the treatment of neovascular age-related macular degeneration (nvAMD). Methods A historical literature review was combined with personal perspectives from the introduction of OCT imaging and the early clinical use of vascular endothelial growth factor (VEGF) inhibitors. Results At the time that OCT emerged, the gold standard for imaging of nvAMD was fluorescein angiography (FA), a time-consuming, dye-based, invasive technique that provided en face images of the retina and was used to characterize leakage, perfusion status, and the types of macular neovascularization (MNV). In comparison, OCT imaging was a fast, safe, noninvasive technique that complemented FA imaging by providing cross-sectional images of the macula. OCT was able to visualize and quantify the macular fluid that was associated with the presence of excess VEGF, which was identified by intraretinal fluid, subretinal fluid, and fluid under the retinal pigment epithelium (RPE). Clinicians quickly appreciated the benefits of OCT imaging for following macular fluid after anti-VEGF therapy. By observing the qualitative and quantitative changes in macular fluid depicted by OCT imaging, clinicians were empowered to compare anti-VEGF drugs and move from fixed-dosing regimens to patient-specific dosing strategies requiring fewer injections. Conclusions Optical coherence tomography imaging was adopted as a VEGF-meter, a method to detect excess VEGF, and evolved to become the gold standard imaging strategy for diagnosing nvAMD, assessing treatment responses to anti-VEGF drugs, deciding when to re-treat, and evaluating disease progression. PMID:27409464

  19. The Incidence and Progression of Age-Related Macular Degeneration over 15 Years: The Blue Mountains Eye Study.

    PubMed

    Joachim, Nichole; Mitchell, Paul; Burlutsky, George; Kifley, Annette; Wang, Jie Jin

    2015-12-01

    To assess the 15-year incidence and progression of age-related macular degeneration (AMD) in an older Australian population. Population-based cohort study. Blue Mountains Eye Study (BMES) participants (n = 3654) aged 49+ years were examined during 1992-1994. Of these, 2334 (75.8% of survivors) were reexamined after 5 years (1997-1999), 1952 (76.7% of survivors) after 10 years (2002-2004), and 1149 (56.1% of survivors) after 15 years (2007-2010). Color retinal photographs were taken, and comprehensive questionnaires were administered at each visit and DNA was genotyped. Retinal photographic grading was performed by the same graders following the Wisconsin AMD grading protocol. Side-by-side comparisons were used to confirm newly developed AMD lesions. Incidence was estimated using Kaplan-Meier estimates. Associations of AMD incidence with age, sex, smoking status, presence of the complement factor H (CFH)-rs1061170 and age-related maculopathy susceptibility 2 (ARMS2)-rs10490924 polymorphisms, and fish consumption were analyzed using discrete logistic regression models. Generalized estimation equation models were used to assess the risk of incident late AMD associated with baseline AMD lesion characteristics. The 15-year incidence and progression of AMD, and associated factors. The 15-year incidence was 22.7% for early AMD and 6.8% for late AMD. After adjusting for competing risks, early and late AMD incidence were 15.1% and 4.1%, respectively. Age was strongly associated with early and late AMD incidence (both P < 0.0001). After age standardization to the Beaver Dam Eye Study (BDES) population, early and late AMD incidence in the BMES were 13.1% and 3.3%, respectively. Female sex and the presence of both risk alleles of CFH-rs1061170 or ARMS2-rs10490924 were independently associated with early AMD incidence, whereas current smoking and presence of ≥1 risk allele of CFH-rs1061170 or ARMS2-rs10490924 were associated with late AMD incidence. Fish consumption was

  20. HLA class II genotypes are not associated with age related macular degeneration in a case-control, population-based study

    PubMed Central

    Pappas, Derek; Hollenbach, Jill; Coleman, Anne L.; Gorin, Michael B.; Yu, Fe; Williams, Kevin; Noble, Janelle; Tranah, Gregory J.

    2015-01-01

    Multiple lines of evidence support an immunologic basis and genetic disposition for the development of age-related macular degeneration (AMD). Comprehensive Human Leukocyte Antigens (HLA) class II typing at four loci (DRB1, DQA1, DQB1, and DPB1) was assessed using next generation sequencing methods and tested for association with Age-related Macular Degeneration (AMD) in a case-control study of 456 AMD cases and 499 controls from the population-based Study of Osteoporotic Fractures (SOF) cohort. No statistically significant associations were identified for any of the class II loci and a previously identified association between DRB1*13:01 was not replicated in this dataset. These results reported here suggest that common HLA class II genetic variation does not contribute to AMD disease risk. PMID:25665771

  1. HLA class II genotypes are not associated with age related macular degeneration in a case-control, population-based study.

    PubMed

    Pappas, Derek; Hollenbach, Jill; Coleman, Anne L; Gorin, Michael B; Yu, Fe; Williams, Kevin; Noble, Janelle; Tranah, Gregory J

    2015-03-01

    Multiple lines of evidence support an immunologic basis and genetic disposition for the development of age-related macular degeneration (AMD). Comprehensive human leukocyte antigens (HLA) class II typing at four loci (DRB1, DQA1, DQB1, and DPB1) was assessed using next generation sequencing methods and tested for association with age-related macular degeneration (AMD) in a case-control study of 456 AMD cases and 499 controls from the population-based Study of Osteoporotic Fractures (SOF) cohort. No statistically significant associations were identified for any of the class II loci and a previously identified association between DRB1*13:01 was not replicated in this dataset. These results reported here suggest that common HLA class II genetic variation does not contribute to AMD disease risk. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  2. FOUR-YEAR INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION: THE LOS ANGELES LATINO EYE STUDY

    PubMed Central

    Varma, Rohit; Foong, Athena W.P.; Lai, Mei-Ying; Choudhury, Farzana; Klein, Ronald; Azen, Stanley P.

    2011-01-01

    Purpose To estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). Design Population-based cohort study. Methods A comprehensive ophthalmologic examination including stereoscopic fundus photography was performed on adult Latinos at baseline and follow-up. Photographs were graded using a modified Wisconsin Age-Related Maculopathy Grading System. For estimations of incidence and progression of AMD, the Age Related Eye Disease Study Scale was used. Main outcome measures are incidence and progression of early AMD (drusen type, drusen size, and retinal pigmentary abnormalities) and advanced AMD (exudative AMD and geographic atrophy). Results 4,658/6100 (76%) completed the follow-up examination. The 4-year incidence of early AMD was 7.5% (95%CI:6.6,8.4) and advanced AMD was 0.2% (95%CI:0.1,0.4). Progression of any AMD occurred in 9.3% (95%CI:8.4,10.3) of at-risk participants. Incidence and progression increased with age. Incidence of early AMD in the second eye (10.8%) was higher than incidence in the first eye (6.9%). Baseline presence of soft indistinct large drusen≥250μm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy, and exudative AMD than smaller or hard or soft distinct drusen. Conclusions Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites. While incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Older persons and those with soft indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft indistinct large drusen. PMID:20399926

  3. Association of neovascular age-related macular degeneration with month and season of birth in Italy.

    PubMed

    Longo, Antonio; Casuccio, Alessandra; Pani, Luca; Avitabile, Teresio; Cillino, Salvatore; Uva, Maurizio G; Bonfiglio, Vincenza; Russo, Andrea; Parisi, Guglielmo; Cennamo, Gilda; Furino, Claudio; Parravano, Mariacristina; Xoxi, Entela; Reibaldi, Michele

    2016-12-19

    In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925-1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined.

  4. Age-related macular degeneration: clinical findings, histopathology and imaging techniques.

    PubMed

    Zarbin, Marco A; Casaroli-Marano, Ricardo P; Rosenfeld, Philip J

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness among people over age 55 years in industrialized countries. Known major risk factors for AMD include: age >55 years, history of smoking, white race, and mutations in various components of the complement system. Early AMD is characterized by the presence of drusen and pigmentary abnormalities. Late AMD is associated with central visual loss and is characterized by the presence of choroidal neovascularization and/or geographic atrophy. Early AMD is associated with a number of biochemical abnormalities including oxidative damage to retinal pigment epithelium (RPE) cells, complement deposition in the RPE-Bruch's membrane-choriocapillaris complex, lipidization of Bruch's membrane, and extracellular matrix abnormalities (e.g. collagen crosslinking, advanced glycation end product formation). Antiangiogenic drugs block the vascular leakage associated with choroidal new vessels, thus reducing retinal edema and stabilizing or restoring vision. At this time, there are no proven effective treatments for the nonexudative complications of AMD. Modern ocular imaging technologies (including spectral domain and phase variance optical coherence tomography, short- and long-wavelength fundus autofluorescence, adaptive optics-scanning laser ophthalmoscopy, and near-infrared reflectance) enable one to follow changes in the RPE, photoreceptors, and choriocapillaris quantitatively as the disease progresses. In addition, one can quantitatively assess the volume of drusen and areas of atrophy. These data, when correlated with the known histopathology of AMD, may provide useful measures of treatment efficacy that are likely to be more sensitive and reproducible than conventional end points such as visual acuity and rate of enlargement of geographic atrophy. As a result, these imaging technologies may be valuable in assessing the effects of cell-based therapy for patients with AMD.

  5. Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.

    PubMed

    Mousa, Shaker A; Mousa, Shaymaa S

    2010-06-01

    Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized.

  6. Association of neovascular age-related macular degeneration with month and season of birth in Italy

    PubMed Central

    Longo, Antonio; Casuccio, Alessandra; Pani, Luca; Avitabile, Teresio; Cillino, Salvatore; Uva, Maurizio G.; Bonfiglio, Vincenza; Russo, Andrea; Parisi, Guglielmo; Cennamo, Gilda; Furino, Claudio; Parravano, Mariacristina; Xoxi, Entela; Reibaldi, Michele

    2017-01-01

    In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925–1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined. PMID:27997361

  7. Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women

    PubMed Central

    Millen, Amy E.; Voland, Rick; Sondel, Sherie A.; Parekh, Niyati; Horst, Ronald L.; Wallace, Robert B.; Hageman, Gregory S.; Chappell, Rick; Blodi, Barbara A.; Klein, Michael L.; Gehrs, Karen M.; Sarto, Gloria E.; Mares, Julie A.

    2010-01-01

    Objective The relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated among participants of the Carotenoids in Age-Related Eye Disease Study. Methods Stereoscopic fundus photographs, taken from 2001–2004, assessed AMD status. Baseline (1994–1998) serum samples were available for 25(OH)D assays in 1,313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n=241), among 1,287 without advanced disease, were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use. Results In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs. 1=0.79, 95% CI=0.50–1.24; p for trend=0.47). A significant age interaction (p=0.0025) suggested selective mortality bias in women ≥75 years: serum 25(OH)D was associated with decreased odds of early AMD in women <75 years (n=968) and increased odds in women ≥75 years (n=319) (OR for quintile 5 vs. 1=0.52, 95% CI=0.29–0.91; p for trend=0.02 and 1.76, 95% CI=0.77–4.13; p for trend=0.05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women <75 years. Additionally, among women <75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight. Conclusions High serum 25(OH)D concentrations may protect against early AMD in women <75 years. PMID:21482873

  8. Association between Previous Cataract Surgery and Age-Related Macular Degeneration.

    PubMed

    Rim, Tyler Hyungtaek; Lee, Christopher Seungkyu; Lee, Sung Chul; Kim, Sangah; Kim, Sung Soo; Epidemiologic Survey Committee Of The Korean Ophthalmological Society

    2017-01-01

    To assess the association between age-related macular degeneration (AMD) and previous cataract surgery. We studied 17,987 randomly selected participants from the Korea National Health and Nutrition Examination Survey who were aged ≥40 years and underwent additional ophthalmologic examinations in 2008‒12. The associations between previous cataract surgery and early/late AMD were identified using multivariate logistic regression analysis of data from right or left eyes. Clustered multivariate logistic regression analysis was performed using both eyes to assess inter-eye correlation in same subject. Previous cataract surgery and cataract subtypes were based on slit-lamp examination without pupil dilation. Early and late AMD diagnoses were based on non-mydriatic digital retinal image. By univariate logistic regression, both early and late AMD prevalence were higher in subjects with pseudophakia/aphakia compared to subjects with cataract as a reference group, or subjects with phakic eye (including clear lens) as a reference group. In univariate logistic regression, both early and late AMD prevalence were higher in eyes with cataract or pseudo/aphakia compared to eyes with clear lens. However, after adjusting for age with multivariate logistic regression, all statistically significant differences in AMD prevalence among subgroups disappeared. We found no association between the previous cataract surgery and increased early/late AMD risk in our representative, large, national patient database. This suggests that increasing age, and not cataract surgery history, is predictive of AMD risk. These findings are limited by cross-sectional study and need to be replicated by other longitudinal observational studies.

  9. [Retina transplantation in exudative form of age-related macular degeneration].

    PubMed

    Figurska, Małgorzata; Stankiewicz, Andrzej

    2002-01-01

    The paper presents different techniques of macular translocation in exudative form of AMD, including particularly retinal detachment followed by retinotomy, limited macular translocation with chorioscleral infolding and outfolding by scleral imbrication.

  10. Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

    NASA Astrophysics Data System (ADS)

    Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

    2003-03-01

    Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

  11. Cardiovascular Risk Factors and Age-related Macular Degeneration: The Los Angeles Latino Eye Study

    PubMed Central

    Fraser-Bell, Samantha; Wu, Joanne; Klein, Ronald; Azen, Stanley P.; Hooper, Claire; Foong, Athena W. P.; Varma, Rohit

    2008-01-01

    Purpose To assess the association of cardiovascular risk factors, ocular perfusion pressure with early and advanced age-related macular degeneration (AMD) in Latinos. Design Population-based, cross-sectional study. Methods Data were collected from a population-based sample of self-identified adult Latinos using standardized protocols for assessing blood pressure and intraocular pressure (IOP) measurement and stereoscopic macular photography. Hypertension was defined as either a history of hypertension or systolic blood pressure (SBP) >140mmHg +/− diastolic blood pressure (DBP) ≥85mmHg. Ocular perfusion pressure (OPP) was defined as the difference between mean arterial blood pressure and IOP. AMD was diagnosed from photographic grading by masked trained graders. Logistic regression was used to assess associations. Results Gradable retinal photographs were available in 5875 participants. After adjusting for age, sex, and cigarette smoking, higher DBP and uncontrolled diastolic hypertension were associated with exudative AMD (Odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1−2.8; and OR, 3.3; CI, 1.2−9.3, respectively). Higher OPP was associated with a decreased risk of GA (OR, 0.4 per 10mmHg; CI, 0.3−0.5). Low pulse pressure was associated with a lower risk of exudative AMD (OR, 0.2; CI, 0.1−0.6). Obesity was associated with increased retinal pigment (OR, 1.6; CI, 1.0−2.3). Conclusion These data suggest that in Latinos cardiovascular risk factors may play a role in advanced AMD. Given that Latinos have a high prevalence of cardiovascular risk factors, an intervention aimed at reducing these risk factors may also have a beneficial impact on the risk of having early and advanced AMD. PMID:18222193

  12. The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field1234

    PubMed Central

    Neuringer, Martha

    2012-01-01

    Age-related macular degeneration (AMD) is the primary cause of vision loss in elderly people of western European ancestry. Genetic, dietary, and environmental factors affect tissue concentrations of macular xanthophylls (MXs) within retinal cell types manifesting AMD pathology. In this article we review the history and state of science on the putative role of the MXs (lutein, zeaxanthin, and meso-zeaxanthin) in AMD and report findings on AMD-associated genes encoding enzymes, transporters, ligands, and receptors affecting or affected by MXs. We then use this context to discuss emerging research opportunities that offer promise for meaningful investigation and inference in the field. PMID:23053548

  13. Recent developments in the treatment of age-related macular degeneration.

    PubMed

    Holz, Frank G; Schmitz-Valckenberg, Steffen; Fleckenstein, Monika

    2014-04-01

    Age-related macular degeneration (AMD) is a common cause of visual loss in the elderly, with increasing prevalence due to increasing life expectancy. While the introduction of anti-VEGF therapy has improved outcomes, there are still major unmet needs and gaps in the understanding of underlying biological processes. These include early, intermediate, and atrophic disease stages. Recent studies have assessed therapeutic approaches addressing various disease-associated pathways, including complement inhibitors. Drug-delivery aspects are also relevant, as many agents have to be administered repeatedly. Herein, relevant pathogenetic factors and underlying mechanisms as well as recent and potential therapeutic approaches are reviewed.

  14. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

    PubMed Central

    Ibrahim, Ahmed S.; Mander, Suchreet; Hussein, Khaled A.; Elsherbiny, Nehal M.; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-01-01

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE–photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features. PMID:26885895

  15. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration

    PubMed Central

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-01-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1−/− mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1−/− mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1−/− mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD. PMID:25604058

  16. Retinal Image Classification for the Screening of Age-Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Hijazi, Mohd Hanafi Ahmad; Coenen, Frans; Zheng, Yalin

    Age-related Macular Degeneration (AMD) is the most common cause of blindness in old-age. Early identification of AMD can allow for mitigation (but not cure). One of the fist symptoms of AMD is the presence of fatty deposits, called drusen, on the retina. The presence of drusen may be identified through inspection of retina images. Given the aging global population, the prevalence of AMD is increasing. Many health authorities therefore run screening programmes. The automation, or at least partial automation, of retina image screening is therefore seen as beneficial. This paper describes a Case Based Reasoning (CBR) approach to retina image classification to provide support for AMD screening programmes. In the proposed approach images are represented in the form of spatial-histograms that store both colour and spatial image information. Each retina image is represented using a series of histograms each encapsulated as a time series curve. The Case Base (CB) is populated with a labelled set of such curves. New cases are classified by finding the most similar case (curve) in the CB. Similarity checking is achieved using the Dynamic Time warping (DTW).

  17. Age-related macular degeneration: genome-wide association studies to translation.

    PubMed

    Black, James R M; Clark, Simon J

    2016-04-01

    In recent years, genome-wide association studies (GWAS), which are able to analyze the contribution to disease of genetic variations that are common within a population, have attracted considerable investment. Despite identifying genetic variants for many conditions, they have been criticized for yielding data with minimal clinical utility. However, in this regard, age-related macular degeneration (AMD), the most common form of blindness in the Western world, is a striking exception. Through GWAS, common genetic variants at a number of loci have been discovered. Two loci in particular, including genes of the complement cascade on chromosome 1 and the ARMS2/HTRA1 genes on chromosome 10, have been shown to convey significantly increased susceptibility to developing AMD. Today, although it is possible to screen individuals for a genetic predisposition to the disease, effective interventional strategies for those at risk of developing AMD are scarce. Ongoing research in this area is nonetheless promising. After providing brief overviews of AMD and common disease genetics, we outline the main recent advances in the understanding of AMD, particularly those made through GWAS. Finally, the true merit of these findings and their current and potential translational value is examined.Genet Med 18 4, 283-289.

  18. Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review

    PubMed Central

    Carneiro, Ângela

    2017-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. In this narrative review, we will summarize the nutritional interventions evaluated in numerous observational studies and a few randomized clinical trials. The AREDS and AREDS2 studies demonstrated that supplements including vitamins C and E, beta-carotene, and zinc may reduce the progression to advanced AMD, in some patients, by 25% in five years. This is one of the few nutritional supplements known to have beneficial effects in any eye disease. Lutein/zeaxanthin supplementation may have beneficial effects in some individuals whereas omega-3 fatty acids supplementation needs to be further investigated and supported by more evidence. Genetic factors may explain the different patterns of response and explain differences found among individuals. More importantly, a combination of lifestyle behaviors such as the avoidance of smoking, physical activity, and the adoption of a healthy dietary pattern like the Mediterranean diet was associated with a lower prevalence of AMD. The adoption of these lifestyles may reduce the prevalence of the early stages of AMD and decrease the number of individuals who develop advanced AMD and consequently the onerous and climbing costs associated with the treatment of this disease. PMID:28154734

  19. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    PubMed Central

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

  20. Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review.

    PubMed

    Carneiro, Ângela; Andrade, José Paulo

    2017-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. In this narrative review, we will summarize the nutritional interventions evaluated in numerous observational studies and a few randomized clinical trials. The AREDS and AREDS2 studies demonstrated that supplements including vitamins C and E, beta-carotene, and zinc may reduce the progression to advanced AMD, in some patients, by 25% in five years. This is one of the few nutritional supplements known to have beneficial effects in any eye disease. Lutein/zeaxanthin supplementation may have beneficial effects in some individuals whereas omega-3 fatty acids supplementation needs to be further investigated and supported by more evidence. Genetic factors may explain the different patterns of response and explain differences found among individuals. More importantly, a combination of lifestyle behaviors such as the avoidance of smoking, physical activity, and the adoption of a healthy dietary pattern like the Mediterranean diet was associated with a lower prevalence of AMD. The adoption of these lifestyles may reduce the prevalence of the early stages of AMD and decrease the number of individuals who develop advanced AMD and consequently the onerous and climbing costs associated with the treatment of this disease.

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

    PubMed Central

    Keane, Pearse A; de Salvo, Gabriella; Sim, Dawn A; Goverdhan, Srini; Agrawal, Rupesh; Tufail, Adnan

    2015-01-01

    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. PMID:25733802

  2. Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration

    PubMed Central

    Yu, Yi; Triebwasser, Michael P.; Wong, Edwin K. S.; Schramm, Elizabeth C.; Thomas, Brett; Reynolds, Robyn; Mardis, Elaine R.; Atkinson, John P.; Daly, Mark; Raychaudhuri, Soumya; Kavanagh, David; Seddon, Johanna M.

    2014-01-01

    We sequenced the whole exome of 35 cases and 7 controls from 9 age-related macular degeneration (AMD) families in whom known common genetic risk alleles could not explain their high disease burden and/or their early-onset advanced disease. Two families harbored novel rare mutations in CFH (R53C and D90G). R53C segregates perfectly with AMD in 11 cases (heterozygous) and 1 elderly control (reference allele) (LOD = 5.07, P = 6.7 × 10−7). In an independent cohort, 4 out of 1676 cases but none of the 745 examined controls or 4300 NHBLI Exome Sequencing Project (ESP) samples carried the R53C mutation (P = 0.0039). In another family of six siblings, D90G similarly segregated with AMD in five cases and one control (LOD = 1.22, P = 0.009). No other sample in our large cohort or the ESP had this mutation. Functional studies demonstrated that R53C decreased the ability of FH to perform decay accelerating activity. D90G exhibited a decrease in cofactor-mediated inactivation. Both of these changes would lead to a loss of regulatory activity, resulting in excessive alternative pathway activation. This study represents an initial application of the whole-exome strategy to families with early-onset AMD. It successfully identified high impact alleles leading to clearer functional insight into AMD etiopathogenesis. PMID:24847005

  3. Cost-Effectiveness Models in Age-Related Macular Degeneration: Issues and Challenges.

    PubMed

    Schmier, Jordana K; Hulme-Lowe, Carolyn K

    2016-03-01

    Age-related macular degeneration (AMD) is a common ophthalmic condition that can have few symptoms in its early stage but can progress to major visual impairment. While there are no treatments for early-stage AMD, there are multiple modalities of treatment for advanced disease. Given the increasing prevalence of the disease, there are dozens of analyses of cost effectiveness of AMD treatments, but methods and approaches vary broadly. The goal of this review was to identify, characterize, and critique published models in AMD and provide guidance for their interpretation. After a literature review was performed to identify studies, and exclusion criteria applied to limit the review to studies comparing treatments for AMD, we compared methods across the 36 studies meeting the review criteria. To some extent, variation was related to targeting different audiences or acknowledging the most appropriate population for a given treatment. However, the review identified potential areas of uncertainty and difficulty in interpretation, particularly regarding duration of observation periods and the importance of visual acuity as an endpoint or a proxy for patient-reported utilities. We urge thoughtful consideration of these study characteristics when comparing results.

  4. Ex Vivo Confocal Spectroscopy of Autofluorescence in Age-Related Macular Degeneration

    PubMed Central

    Kaluzny, Joel; Purta, Patryk; Poskin, Zach; Rogers, Jeremy D.; Fawzi, Amani A.

    2016-01-01

    Purpose We investigated the autofluorescence (AF) signature of the microscopic features of retina with age-related macular degeneration (AMD) using 488 nm excitation. Methods 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. Results 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). Conclusions 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. PMID:27631087