WorldWideScience

Sample records for age-related macular degeneration

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

    Science.gov (United States)

    2016-03-22

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

  2. Age-related macular degeneration

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  3. [Age-related macular degeneration].

    Science.gov (United States)

    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. PMID:25715554

  4. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    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…

  5. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    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,…

  6. Pharmacogenetics and Age-Related Macular Degeneration

    OpenAIRE

    Brantley, Milam A; Schwartz, Stephen G.

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical tri...

  7. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

    @@ Age-related macular degeneration(AMD)is the most important cause of blindness in persons over 55 years of age in the Western world.In view of the increasing life expectancy we can assume that the problem will increase dramatically over the coming decades unless preventive or therapeutic measures are developed.Towards this goal many groups all over the world have performed epidemiological studies to identify potential risk factors for AMD.

  8. Mechanisms of age-related macular degeneration

    OpenAIRE

    Ambati, Jayakrishna; Fowler, Benjamin J.

    2012-01-01

    Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments...

  9. Animal models of age related macular degeneration

    OpenAIRE

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

    2012-01-01

    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 ...

  10. Depression in Age-Related Macular Degeneration

    OpenAIRE

    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 depressio...

  11. Pharmacogenetics and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Stephen G. Schwartz

    2011-01-01

    Full Text Available Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent.

  12. Pharmacogenetics and age-related macular degeneration.

    Science.gov (United States)

    Schwartz, Stephen G; Brantley, Milam A

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID:22046503

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  14. Statistical physics of age related macular degeneration

    Science.gov (United States)

    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.

  15. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  16. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  17. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  18. Precursors of Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Linneberg, Allan; Larsen, Michael

    2013-01-01

    PURPOSE: To investigate associations of small, hard macular drusen and larger macular drusen with obesity-related risk factors. METHODS: Cross-sectional study of 888 subjects aged 30-60 years characterized using anthropometric measurements and blood sample analyses. Physical activity was assessed...... by questionnaire. Digital grayscale fundus photographs were recorded in red-free illumination and graded for the presence of macular drusen >63µm in either eye and the presence of 20 or more small, hard macular drusen as a mean of both eyes. RESULTS: Macular drusen >63µm were associated with the...... level of physical activity, the age- and sex adjusted odds ratio being 0.33 (95% confidence interval 0.13-0.82, P=0.016) for participants who were physically active more than 7 h/week compared with participants active 0-2 h/week. In women, macular drusen >63µm were associated with higher serum...

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

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2015-11-01

    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 as a result of its unique anatomic and physiologic 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, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, 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 age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. PMID:26292978

  20. Genetics Home Reference: age-related macular degeneration

    Science.gov (United States)

    ... and zinc), obesity, and exposure to ultraviolet (UV) rays from sunlight. However, studies of these factors in age-related macular degeneration have had conflicting ... Information What is a gene? What is a gene mutation and how do mutations occur? How can gene ...

  1. Effects of vitrectomy on age-related macular degeneration

    NARCIS (Netherlands)

    Roller, A. Brock; Mahajan, Vinit B.; Boldt, H. Culver; Abramoff, M.D.; Russell, Stephen R.; Folk, James C.

    2010-01-01

    Purpose To determine whether vitrectomy alters the long-term progression of age-related macular degeneration (AMD). Design Retrospective case-control study. Participants Forty-four eyes of 22 patients with AMD who underwent vitrectomy in 1 eye were included in the study. The progression of AMD at

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

    Science.gov (United States)

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

    2012-01-01

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

  3. Radiation treatment for age-related macular degeneration

    International Nuclear Information System (INIS)

    Fifteen eyes of age-related macular degeneration were treated by low-dose radiation. All the affected eyes had subfoveal neovascular membrane. Seventeen nontreated eyes with similar macular lesion served as control. Radiation was performed using photon beam at 6MV. Each eye received daily dose of 2 Gy for 5 consecutive days. When evaluated 9 to 12 months after treatment, the size of neovascular membrane had decreased in 47% of treated eyes and 7% of control eyes. The visual acuity improved by 2 lines or more in 13% of treated eyes and in none of control eyes. When the initial neovascular membrane was less than 1.5 disc diameter in size, the visual acuity had improved or remained stationary in 90% of treated eyes and in 36% of control eyes. The findings show the potential beneficial effect of radiation for age-related macular degeneration. (author)

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

    NARCIS (Netherlands)

    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: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mou

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

    NARCIS (Netherlands)

    R. Klein (Ronald); C.E. Myers (Chelsea); G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); X. Gao (Xiaoyi); P.T.V.M. de Jong (Paulus); T.A. Sivakumaran (Theru); G. Burlutsky (George); R. McKean-Cowdin (Roberta); A. Hofman (Albert); S.K. Iyengar (Sudha); K.E. Lee (Kristine); B.H. Stricker; J.R. Vingerling (Hans); P. Mitchell (Paul); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline); J.J. Wang (Jie Jin)

    2014-01-01

    textabstractPurpose 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: A total of 6950 participants from the Beaver Dam Eye Study (BDES),

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

    Science.gov (United States)

    ... 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 ...

  7. Genetic factors of age-related macular degeneration

    OpenAIRE

    Tuo, Jingsheng; Bojanowski, Christine M.; Chan, Chi-Chao

    2004-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic compone...

  8. Retinal phagocytes in age-related macular degeneration

    OpenAIRE

    Kim, Soo-Young

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in industrial countries. Vision loss caused by AMD results from geographic atrophy (dry AMD) and/or choroidal neovascularization (wet AMD). Presently, the etiology and pathogenesis of AMD is not fully understood and there is no effective treatment. Oxidative stress in retinal pigment epithelial (RPE) cells is considered to be one of the major factors contributing to the pathogenesis of AMD. Also retinal glia, as scavenge...

  9. Pinpointing the Earliest Defects in Age-Related Macular Degeneration

    OpenAIRE

    Magnusson, Kristinn P; Duan, Shan; Sigurdsson, Haraldur; Petursson, Hjorvar; Yang, Zhenglin; Zhao, Yu; Bernstein, Paul S; Ge, Jian; Jonasson, Fridbert; Stefansson, Einar; Helgadottir, Gudleif; Zabriskie, Norman A.; Jonsson, Thorlakur; Björnsson, Asgeir; Thorlacius, Theodora

    2005-01-01

    Background Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in th...

  10. Oxidative damage and age-related macular degeneration

    OpenAIRE

    Winkler, Barry S.; Boulton, Michael E.; Gottsch, John D.; Sternberg, Paul

    1999-01-01

    This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD). The emphasis is placed on the generation of oxidants and free radicals and the protective effects of antioxidants in the outer retina, with specific emphasis on the photoreceptor cells, the retinal pigment epithelium and the choriocapillaris. The starting points include a discussion and a definition of what radicals are, their endogenous sources, how they react, ...

  11. Ranibizumab in neovascular age-related macular degeneration

    OpenAIRE

    Eng, Kenneth T; Kertes, Peter J

    2006-01-01

    Neovascular age-related macular degeneration (AMD) is a visually devastating condition resulting from choroidal neovascularization and secondary photoreceptor loss. Ranibizumab and bevacizumab are medications that target vascular endothelial growth factor (VEGF). While other therapies have demonstrated some ability to reduce the risk of losing vision from neovascular AMD, most patients continue to lose some degree of central visual acuity. There is growing evidence that intravitreal administr...

  12. Squalamine lactate for exudative age-related macular degeneration.

    Science.gov (United States)

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies. PMID:16935213

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

    Science.gov (United States)

    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. PMID:26742632

  14. Is Alzheimer disease related to age-related macular degeneration?

    OpenAIRE

    DEMİRCİ, Seden; GÜNEŞ, ALİME; Demi̇rci̇, Kadi̇r; DEMİRCİ, SERPİL; Tök, Levent; Tök, Özlem

    2015-01-01

    Background/aim: To compare the cognitive functions and define the frequency of Alzheimer disease (AD) between participants with and without age-related macular degeneration (AMD). Materials and methods: Fifty-nine patients with late-stage AMD (74.3 ± 7.3 years) and 49 age-, sex-, and education-matched control subjects were compared for the presence of AD according to the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disea...

  15. Genomic aspects of age-related macular degeneration.

    Science.gov (United States)

    Horie-Inoue, Kuniko; Inoue, Satoshi

    2014-09-19

    Age-related macular degeneration (AMD) is a major late-onset posterior eye disease that causes central vision to deteriorate among elderly populations. The predominant lesion of AMD is the macula, at the interface between the outer retina and the inner choroid. Recent advances in genetics have revealed that inflammatory and angiogenic pathways play critical roles in the pathophysiology of AMD. Genome-wide association studies have identified ARMS2/HTRA1 and CFH as major AMD susceptibility genes. Genetic studies for AMD will contribute to the prevention of central vision loss, the development of new treatment, and the maintenance of quality of vision for productive aging. PMID:25111812

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Yoshihiro Yonekawa

    2015-02-01

    Full Text Available 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.

  18. Radiation therapy for age-related macular degeneration

    International Nuclear Information System (INIS)

    We evaluated the effect of low-dose radiation on age-related macular degeneration in 8 affected eyes. Radiation was applied using photons at 4 MV. Each eye received 10 fractions of 2 Gy per day over 2 weeks. At 6 months after treatment, funduscopic or angiographic findings had either improved or remained unchanged in all the eyes. The visual acuity improved by 2 lines or more in 2 eyes (25%), remained unchanged in 5 eyes (63%) and deteriorated in 1 eye (13%). At the last examination, fundus findings had improved in 2 eyes (25%), remained unchanged in 1 eye (13%) and deteriorated in 5 eyes (63%). The visual acuity had improved or unchanged in 2 eyes each (25%) and deteriorated in 4 eyes (50%). There has been no negative side effects of radiation. Above findings show that low-dose radiation is potentially beneficial for subfoveal or juxtafoveal choroidal neovascularizations in age-related macular degeneration on a short term basis. (author)

  19. Radiation Therapy for Neovascular Age-related Macular Degeneration

    International Nuclear Information System (INIS)

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity

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

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith; Thorlund, Kristian; Christensen, Robin; Vorum, Henrik; Jansen, Jeroen P

    2015-01-01

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

  1. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

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

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

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

  4. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Lund-Andersen, Henrik; Sander, Birgit; Larsen, Michael

    2013-01-01

    To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis.......To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis....

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

    Science.gov (United States)

    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. PMID:26852158

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  7. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

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

  9. Age-Related Macular Degeneration: A Scientometric Analysis

    Science.gov (United States)

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993–2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic’s structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  10. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    Science.gov (United States)

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD. PMID:27348529

  11. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

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

  12. Radiation therapy for age-related macular degeneration

    International Nuclear Information System (INIS)

    We evaluated the effects of low-dose radiation on choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Since Chakravarthy reported the benefits from administration of low-dose external-beam irradiation for CNV, many studies have demonstrated that irradiation could have a beneficial treatment effect, whereas several reports have not. In our hospital, 12 eyes with AMD received 10 Gy of 4 MV photons and the other 9 eyes received 20 Gy. Another 4 eyes were untreated as control. After 6 months of treatment, visual acuity was maintained in 11 eyes, improved in 5 eyes, and deteriorated in 5 eyes of treated patients. In control group, visual acuity was maintained in 1 eye and deteriorated in 3 eyes. The size of CNV regressed in 10 eyes, remained stationary in 2 eyes and progressed in 2 eyes of treated patients, while in control group CNV regressed in 2 eyes and remained stationary in 1 eye. After 12 months some CNV progressed. Although the present result seems to be better than those in previous reports, whether or not the treatment is beneficial has to be awaited. (author)

  13. Automatic age-related macular degeneration detection and staging

    Science.gov (United States)

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

    2013-03-01

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

  14. The Role of Vitamins in the Treatment of Age Related Macular Degeneration

    OpenAIRE

    Mandić, Zdravko; Benčić, Goran; Vatavuk, Zoran

    2004-01-01

    The role of vitamins in the treatment of age related macular degeneration was reviewed. The following studies were selected for review: Eye Disease Case Control Study (EDCCS), Beaver Dam Eye Study, Blue Mountains Eye Study, Pathologies Oculaires Liees a l'Age Study (studija POLA) and Age Related Eye Disease Study (AREDS). These studies showed that antioxidant intake could be recommended in patients with certain forms of age related macular degeneration. A definite answer concerning the role o...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-02

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

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

    Science.gov (United States)

    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. PMID:27220225

  17. Age-Related Macular Degeneration: Genetics and Biology.

    Science.gov (United States)

    Kumaramanickavel, Govindasamy

    2016-01-01

    Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Approximately half a dozen physiological and biochemical cascades are disrupted in the AMD disease genesis, eventually leading to the distortion and disruption of the subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen genetic factors have so far been identified, including the recent ones, through powerful genomic technologies and large robust sample sizes. The noteworthy genetic variants (common and rare) are complement factor H, complement factor H-related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous amount of scientific information generated over the years, diagnostic genetic or biomarker tests are still not available for clinicians to understand the natural course of the disease and its management in a patient. However, further research in the field should reduce this gap not only by aiding the clinician but also through the possibilities of clinical intervention with complement pathway-related inhibitors entering preclinical and clinical trials in the near future. PMID:27488064

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

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

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

    Science.gov (United States)

    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

  1. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo; Wolf, Sebastian; Simader, Christian; Tokaji, Erika; Pilz, Stefan; Weisberger, Annemarie

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

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

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2016-05-01

    Full Text Available 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    2016-01-05

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  6. AGE-RELATED MACULAR DEGENERATION: CURRENT ASPECTS OF PATHOGENESIS AND TREATMENT

    Institute of Scientific and Technical Information of China (English)

    H; P; Heidenkummer

    1991-01-01

    About 1.1 million people are estimated to have age-related macular degeneration in West Germany. Anatomical aspects of the normal macula and physiological ageing processes in the retina will be discribed including alterations in the choroid, in Bruch's membrane, the pigment epithelium and the sensory retina. Risk factors for the development of age-related macular degeneration are age per se, perhaps ethnologic characteristics, ocular characteristics, and perhaps environmental factors. The histopathology...

  7. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  8. Multifocal Electroretinogram Findings after Intravitreal Bevacizumab Injection in Choroidal Neovascularization of Age-Related Macular Degeneration

    OpenAIRE

    Park, Joo Youn; Kim, Seung Hoon; Park, Tae Kwann; Ohn, Young-Hoon

    2011-01-01

    Purpose To evaluate the changes in multifocal electroretinogram (mfERG) and optical coherence tomography (OCT) after intravitreal bevacizumab injection in the treatment of age-related macular degeneration (AMD). Methods Twenty-one eyes with choroidal neovascularization secondary to AMD were studied before and after intravitreal bevacizumab injection for best corrected visual acuity (BCVA), OCT, and mfERG. Results The BCVA improved, while central macular thickness and total macular volume in O...

  9. [Age-related Macular Degeneration in the Japanese].

    Science.gov (United States)

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  10. Quality of life in age-related macular degeneration: a review of the literature

    OpenAIRE

    Bradley Clare; Mitchell Jan

    2006-01-01

    Abstract Background The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is repro...

  11. Quality of life in age-related macular degeneration: a review of the literature

    OpenAIRE

    Bradley, Clare; Mitchell, Jan

    2006-01-01

    The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method: A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is reproduced here. ...

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

    Science.gov (United States)

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

  13. Photodynamic Therapy for Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    Chenjin Jin; Jian Ge; Shaobo Zhou; Huiyi Chen; Xiaojing Zhong; Ruzhang Jiang; Lingyan Chen; Lirong Chen

    2004-01-01

    Purpose: To evaluate short-term effects of single photodynamic therapy (PDT) for agerelated macular degeneration (AMD) accompanied with choroidal neovascularization (CNV).Methods: We analyzed retrospectively the effects of single PDT for 20 patients (20 eyes)with CNV caused by AMD. Corrected visual acuity, fluorescein angiography (FA) and optic coherence tomography (OCT) were examined before and after PDT. All patients were followed up at least 3 months.Results: At the end of 3-month follow-up, 5 eyes had vision progress, 15 eyes had vision stable and no eye had vision deterioration. Fluorescein angiography one week post PDT showed cessation of fluorescein leakage in 8 eyes with predominant classic CNV, and reduction of fluorescein leakage in 12 eyes with minimal classic CNV or occult CNV without classic component. At the 3-month following PDT fluorescein angiography showed fluorescein leakage reappeared in 4 of 8 eyes with predominant classic CNV.Among 12 eyes with minimal classic CNV or occult CNV without classic component, 9eyes showed decreased or unchanged fluorescein leakage, 3 eyes had a progression of fluorescein leakage. Optic coherence tomography showed obvious recovery of serous sensory retinal detachment after PDT.Conclusion: PDT may occlude or inhibit CNV caused by AMD in short term. No obvious side effects were noticed.

  14. Radiation therapy for subfoveal chroidal neovascularization complicating age-related macular degeneration

    International Nuclear Information System (INIS)

    We evaluated the effect of low-dose external beam irradiation on the visual function of 14 eyes with subfoveal chroidal neovascularization complicating age-related macular degeneration. Patient received external beam irradiation at a dose of 20 Gy in 10 fraction of 2 Gy. After treatment the visual function improved in 2 eyes, remained stable in 8 eyes and deteriorated in 4 eyes. At the last examination visual function improved in 1 eyes, remained stable in 2 eyes and deteriorated in 5 eyes. The low-dose irradiation is potentially beneficial for subfoveal chroidal neovascularization complicating age-related macular degeneration. (author)

  15. Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study

    Directory of Open Access Journals (Sweden)

    Dow CT

    2016-01-01

    Full Text Available Coad Thomas Dow,1,2 Calvin B Harley3 1McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA; 2Chippewa Valley Eye Clinic, Eau Claire, Wisconsin, WI, USA; 3Independent Telomere Biology Consultant, Murphys, CA, USA Purpose: Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease.Method: Thirty-eight (38 patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes.Results: The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation] improved 0.97 dB compared to placebo (P-value 0.02 and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04. Conclusion: The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. Keywords: drusen, macular degeneration, micro-perimetry, senescence, telomerase activation, telomere

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

    Directory of Open Access Journals (Sweden)

    Fong AH

    2013-04-01

    Full Text Available Angie HC Fong,1 Timothy YY Lai1,2 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong; 22010 Retina and Macula Centre, Tsimshatsui, Kowloon, Hong Kong Abstract: 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

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

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

    Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  19. Prediction of age-related macular degeneration in the general population: The three continent AMD consortium

    NARCIS (Netherlands)

    G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); C.E. Myers (Chelsea); C.M. van Duijn (Cock); K.E. Lee (Kristine); B.E.K. Klein (Barbara); S.M. Meuer (Stacy); P.T.V.M. de Jong (Paulus); E.G. Holliday (Elizabeth); A.G. Tan (Ava); A.G. Uitterlinden (André); T.A. Sivakumaran (Theru); J. Attia (John); A. Hofman (Albert); P. Mitchell (Paul); J.R. Vingerling (Hans); S.K. Iyengar (Sudha); A.C.J.W. Janssens (Cécile); J.J. Wang (Jie Jin); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline)

    2013-01-01

    textabstractPurpose 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

  20. Complement component C3 and risk of age-related macular degeneration

    NARCIS (Netherlands)

    D.D.G. Despriet; C.M. van Duijn; B.A. Oostra; A.G. Uitterlinden; A. Hofman; A.F. Wright; J.B. ten Brink; A. Bakker; P.T.V.M. de Jong; J.R. Vingerling; A.A.B. Bergen; C.C.W. Klaver

    2009-01-01

    OBJECTIVE: To explore the association between polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of complement factor H (CFH) Y402H, LOC387715 A69S and smoking. DESIGN: Pooled data from the prospective, population

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  5. Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

    Science.gov (United States)

    Wahl, Hans-Werner; Kammerer, Annette; Holz, Frank; Miller, Daniel; Becker, Stefanie; Kaspar, Roman; Himmelsbach, Ines

    2006-01-01

    This study evaluated an emotion-focused and a problem-focused intervention designed for patients with age-related macular degeneration. It found a limited decrease in depression in the emotion-focused group and an increase in active problem orientation and in adaptation to vision loss in the problem-focused group.

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

    Science.gov (United States)

    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...

  7. Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration

    OpenAIRE

    K. O. Akuffo; Nolan, J M; Howard, A. N.; Moran, R.; Stack, J; Klein, R; Klein, B E; Meuer, S M; Sabour-Pickett, S; Thurnham, D I; BEATTY, S

    2015-01-01

    Purpose To compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD). Patients and methods Sixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3...

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    . Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires a......, photodynamic therapy with verteporfin is the treatment of choice. Photodynamic therapy is also effective in eyes with pure occult CNV and evidence of recent disease progression. For new subfoveal CNV with poor vision and recurrent CNV, laser photocoagulation can be considered....... fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography...

  9. Factors related to the effect of radiation treatment for age-related macular degeneration

    International Nuclear Information System (INIS)

    We treated 31 eyes of 30 patients with age-related macular degeneration by 10 sessions of radiation totalling 20 Gy. One year after treatment, 21 eyes (68%) showed improvement in the score of fundus lesions based on funduscopic and fluorescein angiographic findings. The visual acuity, expressed as LogMAR, improved in 20% and remained stationary in 50% of eyes. Improvement in visual acuity was significantly better in eyes with greater amount of exudate before treatment (p<0.01). Posttreatment visual acuity was correlated neither with the amount of subretinal fluid, presence of retinal hemorrhage, the size of subfoveal vascular membrane, nor its type as classified into classic, mainly occult or occult type. Above findings show that radiation is more effective in eyes of age-related macular degeneration with massive exudate. (author)

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

    Science.gov (United States)

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

    2013-12-01

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

  11. Resistance to antivascular endothelial growth factor treatment in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tranos P

    2013-06-01

    Full Text Available Paris Tranos,1 Athanasios Vacalis,1 Solon Asteriadis,1 Stavrenia Koukoula,1 Athanasios Vachtsevanos,1 Georgia Perganta,1 Ilias Georgalas21Retina Centre, Thessaloniki, Greece; 2Department of Ophthalmology, "G Gennimatas" Hospital of Athens, University of Athens, Athens, GreeceAbstract: Age-related macular degeneration (AMD is the main cause of visual impairment and blindness in people aged over 65 years in developed countries. Vascular endothelial growth factor (VEGF is a positive regulator of angiogenesis and its proven role in the pathological neovascularization in wet AMD has provided evidence for the use of anti-VEGF agents as potential therapies. In this study, we review the literature for the possible causes of failure after treatment with anti-VEGF agents and attempt to propose an algorithm of suggestive actions to increase the chances of successful management of such difficult cases.Keywords: antiVEGF, age related macular degeneration, treatment

  12. Tachyphylaxis during ranibizumab treatment of exudative age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Sibel; Doguizi; Sengul; Ozdek; Selcen; Yuksel

    2015-01-01

    <正>Dear Editor,We are intestigators from Turkey primarily studying exudative age-related macular degeneration(AMD).Here we present the results of our retrospective clinical study on tachyphylaxis development during the treatment of exudative AMD with ranibizumab,which,we believe,will form a basis for further prospective studies to predict the drug response in anti-vascular endothelial growth factor

  13. [Clarifying some concepts and clinical significance of refractory or recurrent neovascular age-related macular degeneration].

    Science.gov (United States)

    Zhao, Jingke; Sun, Xiaodong

    2015-11-01

    Anti-VEGF therapy is currently one of the main treatments for neovascular age-related macular degeneration (nAMD). Clinically, patients under standardized anti-VEGF therapy showed different responses, of which recurrences or even insensitivity were found in some patients. However, the specific definitions of these various clinical responses are still unclarified. Therefore, to consolidate and define these concepts are of great importance regarding to future efficacy comparison, treatment response clarification and novel drug switching therapies. PMID:26850580

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

    OpenAIRE

    Mason III JO; Patel SA

    2015-01-01

    John O Mason III,1,2 Shyam A Patel11Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL, USA; 2Retina Consultants of Alabama, Callahan Eye Foundation Hospital, Birmingham, AL, USAObjective: To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry age-related macular degeneration (AMD).Methods: We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD.Results: Eyes w...

  15. Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina

    OpenAIRE

    Singh Brij B; Marwarha Gurdeep; Prasanthi Jaya RP; Dasari Bhanu; Ghribi Othman

    2011-01-01

    Abstract Background Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological hallmarks including β-amyloid (Aβ) accumulation, oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely multi-factorial with several factors such as diet, environment, and genetic susceptibility participating in the pathogenesis of these diseases. Epidemiological studies correlated high plasma cholesterol levels with high incidence of AD, and feeding rabb...

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

    OpenAIRE

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

    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-na...

  17. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

    OpenAIRE

    Evans, J. R.; Lawrenson, J

    2012-01-01

    Background: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD). Objectives: The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD. Search meth...

  18. Age-related macular degeneration: what can a family physician do?

    OpenAIRE

    Latowsky, M L

    1988-01-01

    Age-related macular degeneration (ARMD) is the most common cause of blindness in Canada, and, as the name suggests, its incidence increases rapidly with age. Atrophic maculopathy, one of the forms of ARMD, is associated with only mild to moderate visual loss but is not treatable. On the other hand, exudative maculopathy, another form, is characterized by the formation of neovascular membranes and causes acute visual disturbances; however, it is potentially treatable by means of laser photocoa...

  19. Patients’ knowledge and perspectives on wet age-related macular degeneration and its treatment

    OpenAIRE

    Sushma Kandula; Jeffrey C Lamkin; Teresa Albanese; et al

    2010-01-01

    Sushma Kandula1, Jeffrey C Lamkin1, Teresa Albanese2, Deepak P Edward11Department of Ophthalmology, 2Health Service Research and Education Institute, SUMMA Health System, Akron OH, USASummary: There have been no studies examining the level of understanding age-related macular degeneration (ARMD) patients have about their disease, or their perceptions about intraocular injections as treatment. In this study, patient knowledge about ARMD risk factors was low but patients appeared more optimisti...

  20. Patients’ knowledge and perspectives on wet age-related macular degeneration and its treatment

    OpenAIRE

    Kandula, Sushma; Jeffrey C Lamkin; Albanese, Teresa; Deepak P Edward

    2010-01-01

    Summary: There have been no studies examining the level of understanding age-related macular degeneration (ARMD) patients have about their disease, or their perceptions about intraocular injections as treatment. In this study, patient knowledge about ARMD risk factors was low but patients appeared more optimistic than fearful when confronted with intraocular antivascular endothelial growth factor (anti-VEGF) injections as treatment. Purpose: In recent years there has been an increase in our u...

  1. Low fluence rate photodynamic therapy combined with intravitreal bevacizumab for neovascular age related macular degeneration.

    OpenAIRE

    Costagliola, Ciro; Romano, Mario R.; Rinaldi, Michele; Dell'Omo, Robeto; Chiosi, Flavia; Menzione, Massimo; Semeraro, Francesco

    2010-01-01

    Abstract Aims: to report efficacy and safety of intravitreal bevacizumab (IVB) alone versus IVB plus low fluence PDT in age-related macular degeneration (AMD) patients and to verify the occurrence of a synergistic effect of the combined approach on visual acuity, size and morphology of lesion, as well as on the treatment rate. Method: prospective comparative interventional study on 85 patients with treatment naive classic, or predominantly classic, subfoveal choroid...

  2. Early Signs of Exudative Age-Related Macular Degeneration in Asians

    OpenAIRE

    Sasaki, Mariko; Kawasaki, Ryo; Uchida, Atsuro; Koto, Takashi; Shinoda, Hajime; Tsubota, Kazuo; Wong, Tien Yin; Ozawa, Yoko

    2014-01-01

    ABSTRACT Purpose To investigate the relationship between the early signs of age-related macular degeneration (AMD) and the risk of developing exudative AMD (typical AMD or polypoidal choroidal vasculopathy [PCV]) in the fellow eye of Japanese patients with unilateral exudative AMD, focusing particularly on eyes with only pigmentary abnormality. Methods This study is a retrospective observational consecutive case series. We retrospectively reviewed the medical charts of patients who revisited ...

  3. Exploring the role of VEGF in Indian Age related macular degeneration

    OpenAIRE

    Sharma, Kaushal; Sharma, Neel K.; Singh, Ramandeep; Anand, Akshay

    2015-01-01

    Background Age related macular degeneration (AMD) is major devastating neurodegenerative disorder characterized by progressive irreversible vision loss in the elderly persons. In spite of several genetic and environmental factors, the role of VEGF and CFH predispose the pathological phenomenon in the AMD patients. Purpose The aim of the study was to estimate the VEGF levels in the serum of AMD patients and its correlation with co-morbidity of the participants. Methods The study recruited the ...

  4. Association of diabetes with age-related macular degeneration in the EUREYE study

    OpenAIRE

    Topouzis, F; Anastasopoulos, E.; Augood, C; Bentham, G.C.; Chakravarthy, U; Jong, de, M.C.M.; Rahu, M.; Seland, J.; Soubrane, G.; Tomazzoli, L.; Vingerling, J.R.; Vioque, J.; Young, I. S.; Fletcher, A. E.

    2009-01-01

    Objective: To examine the association between self-reported diabetes history and early or late age-related macular degeneration (AMD) in the European population. Methods: Participants aged 65 years and over in the cross-sectional population-based EUREYE study underwent an eye examination including digital retinal photography. The images were graded at a single centre. A structured questionnaire was administered by trained field workers for putative risk factors for AMD including history of di...

  5. Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

    OpenAIRE

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most ...

  6. MITOCHONDRIAL VARIATION AND THE RISK OF AGE-RELATED MACULAR DEGENERATION ACROSS DIVERSE POPULATIONS

    OpenAIRE

    Restrepo, Nicole A.; Mitchell, Sabrina L.; Goodloe, Robert J.; Murdock, Deborah G.; HAINES, JONANTHAN L.; Crawford, Dana C.

    2015-01-01

    Substantial progress has been made in identifying susceptibility variants for age-related macular degeneration (AMD). The majority of research to identify genetic variants associated with AMD has focused on nuclear genetic variation. While there is some evidence that mitochondrial genetic variation contributes to AMD susceptibility, to date, these studies have been limited to populations of European descent resulting in a lack of data in diverse populations. A major goal of the Epidemiologic ...

  7. Genetic association study of mitochondrial polymorphisms in neovascular age-related macular degeneration

    OpenAIRE

    Tilleul, Julien; Richard, Florence; Puche, Nathalie; Zerbib, Jennyfer; Leveziel, Nicolas; Sahel, Jose Alain; Cohen, Salomon Yves; Korobelnik, Jean-Francois; Feingold, Josue; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel; Souied, Eric H.

    2013-01-01

    Purpose Age-related macular degeneration (AMD) is a multifactorial disease involving genetic and environmental factors. Most of the genetic factors identified so far involve the nuclear genome. Recently, two studies in North America and Australia reported an association between advanced AMD and the mitochondrial T2 haplogroup. Our purpose was to assess this association in a large French population. Methods This case control study included 1,224 patients with neovascular AMD and 559 controls w...

  8. Prevalence of depression and its effect on disability in patients with age-related macular degeneration

    OpenAIRE

    Banerjee Anindya; Kumar Suresh; Kulhara Parmanand; Gupta Amod

    2008-01-01

    Aims: To estimate depression in patients with age-related macular degeneration (AMD) and study the relationships among depression, visual acuity, and disability. Materials and Methods: It was a cross-sectional study with consecutive sampling (n = 53) of patients with AMD aged 50 years and above attending the retina clinic of a tertiary care hospital in North India. Depression, general disability and vision-specific disability were assessed in subjects meeting selection criteria. Assessment...

  9. he Effects of Glaucoma and Age-Related Macular Degeneration on Quality of Life

    OpenAIRE

    Nilüfer Koçak; Behice Elif Onur; Hüseyin Aslankara; Hasan Can Cimilli; Süleyman Kaynak

    2014-01-01

    Objectives: The aim of the study was to assess the depressive and anxiety symptoms and the quality of life (QofL) in patients treated for glaucoma and age-related macular degeneration (AMD). Materials and Methods: Between March 1 and June 30, 2008, 60 outpatients with glaucoma and AMD were included into the study. As controls, sixty patients with similar sociodemographic features and who applied to the Ophthalmology Clinics with refractive errors only were taken. All patients and ...

  10. Epidemiology and Quality of Life of Patients with Age-Related Macular Degeneration

    OpenAIRE

    Synek, Svatopluk; Vojniković, Božo; Pahor, Đana

    2010-01-01

    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 preven...

  11. Recent developments in the management of dry age-related macular degeneration

    OpenAIRE

    Buschini E; Fea AM; Lavia CA; Nassisi M; Pignata G.; Zola M; Grignolo FM

    2015-01-01

    Elisa Buschini, Antonio M Fea, Carlo A Lavia, Marco Nassisi, Giulia Pignata, Marta Zola, Federico M Grignolo Ospedale Oftalmico, Ophthalmic Section, Department of Clinical Pathophysiology, University of Turin, Turin, Italy Abstract: Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Althou...

  12. Treatment of Submacular Haemorrhage in Patients with Neovascular Age Related Macular Degeneration

    OpenAIRE

    Lumi, Xhevat; Šulak, Marko

    2013-01-01

    To evaluate the efficacy of the pneumatic displacement of the submacular haemorrhage combined with the intravitreal injection of the tissue plasminogen activator. We present a retrospective clinical case series of nine eyes of nine patients that were treated with the intravitreal injection of the tissue plasminogen activator and expansile gas for the submacular haemorrhage due to the age related macular degeneration. We evaluated visual acuities and complications. Selected patients were addit...

  13. Intravitreal Bevacizumab for Choroidal Neovascularization Secondary to Non-Age-Related Macular Degeneration

    OpenAIRE

    Salehipour, Masoud; Vafi, Nasser; Doozande, Azade; yaseri, Mehdi

    2010-01-01

    Purpose To report the long-term results of intravitreal bevacizumab (Avastin) therapy for choroidal neovascularization (CNV) secondary to non-age-related macular degeneration (non-AMD). Methods This prospective interventional case series was conducted on patients with non-AMD CNV. All patients received 1.25 mg intravitreal bevacizumab and were followed for at least 18 weeks. Indications for retreatment were decreased visual acuity or recurrence of subretinal fluid or hemorrhage associated wit...

  14. Combination of bevacizumab and bromfenac therapy in age-related macular degeneration: A pilot study

    OpenAIRE

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

    2014-01-01

    Background According to recent studies, the newest strategy for the treatment of exudative age-related macular degeneration is to combine anti-VEGF agents with non-steroid anti-inflammatory drugs (NSAIDs) such as nepafenac and bromfenac to decrease the frequency of intravitreal injections. Since most research has focused on ranibizumab, the aim of this study is to evaluate whether an alternative drug such as bevacizumab could lead to similar outcomes. Material/Methods The study was conducted ...

  15. TCCR/WSX-1 is a novel angiogenic factor in age-related macular degeneration

    OpenAIRE

    Sung, Ho Jin; Han, Jung Il; Lee, Ji Won; Uhm, Ki Bang; Heo, Kyun

    2012-01-01

    Purpose Age-related macular degeneration (AMD) is the major cause of blindness among persons aged 60 years and older. The current approved therapies for AMD are exclusively limited to inhibiting vascular endothelial growth factor. However, substantial improvement in vision occurs in only one-third of patients treated with vascular endothelial growth factor antagonists, and one-sixth of treated patients still progress to legal blindness. Therefore, more specific targets are needed to treat AMD...

  16. Comparison of life quality scores of ranibizumab-treated patients with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Saadet Arslan

    2016-03-01

    Full Text Available Purpose: To evaluate the visual acuity, fluorescein angiography, optic coherence tomography and life quality of patients diagnosed with exudative age-related macular degeneration and administered with intravitreal Ranibizumab injection. Material and Methods: This study included of 48 different patients who were diagnosed as exudative age-related macular degeneration and administered with ranibizumab injection. In this study, demographic characteristics, pre- and post-injection corrected visual acuity, angiography, optic coherence tomography alteration and the scores of quality of life questionnaire were prospectively analyzed. Results: The patients were followed up for 20+/-1 months on average. After ranibizumab injection, 12 patients (25% gained and #8805;3 lines of visual acuity, 28 patients (58.3% gained and #8804;3 lines of visual acuity, 6 patients (12.5% lost and #8804;3 lines of visual acuity and 2 patients (4.2% lost and #8805;3 lines of visual acuity. The increase in Early Treatment Diabetic Retinopathy Study was lower in patients with Hypertension and positive family history In this study, it was determined that The National Eye Institute Visual Function Questionnaire score increased in patients with improving visual acuity after ranibizumab injection and the difference was statistically significant. Conclusion: Visual acuity was found to improve in patients with exudative age-related macular degeneration and treated with intravitreal ranibizumab injection. The National Eye Institute Visual Function Questionnaire provided reliable results in patients with age-related macular degeneration and the questionnaire score was determined to increase following the treatment. [Cukurova Med J 2016; 41(1.000: 61-68

  17. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    Science.gov (United States)

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  18. Stereotactic radiotherapy for wet age-related macular degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Neffendorf JE

    2015-09-01

    Full Text Available James E Neffendorf, Timothy L Jackson Department of Ophthalmology, School of Medicine, King’s College London, London, United Kingdom Abstract: Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger randomized controlled trial (STAR is underway. Keywords: wet age-related macular degeneration, radiation therapy, stereotactic radiotherapy, vascular endothelial growth factor

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

    OpenAIRE

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

    2014-01-01

    Background Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults. Anti-retinal autoantibodies (AAbs) have been found in individuals with AMD. The goal of the study was to determine the AAb specificity in different stages of AMD, and determine whether there is a prevalent AAb signature. Methods Sera of 134 participants in the Age-related Eye Disease Study were analyzed for anti-retinal AAbs by western blotting. The subjects were classified by diagno...

  20. Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

    Directory of Open Access Journals (Sweden)

    Marilita M. Moschos

    2014-01-01

    Full Text Available Age-related macular degeneration (ARMD is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

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

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara B; Fuchs, Josefine; Hansen, Louise Kim Hillerup; Larsen, Michael; Dornonville de la Cour, Morten; Lund-Andersen, Henrik; Sander, Birgit

    2013-01-01

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

  2. Differences in spectral absorption properties between active neovascular macular degeneration and mild age related maculopathy.

    Science.gov (United States)

    Balaskas, Konstantinos; Nourrit, Vincent; Dinsdale, Michelle; Henson, David B; Aslam, Tariq

    2013-05-01

    This study examines the differences in spectral absorption properties between the maculae of patients with active neovascular macular degeneration and those with early age related maculopathy (ARM). Patients attending for management of neovascular age related macular degeneration (AMD) underwent multispectral imaging with a system comprising of a modified digital fundus camera coupled with a 250-W tungsten-halogen lamp and a liquid crystal fast-tuneable filter. Images were obtained at 8 wavelengths between 496 and 700 nm. Aligned images were used to generate a DLA (differential light absorption, a measure of spectral absorption properties) map of the macular area. DLA maps were generated for both eyes of 10 sequential patients attending for anti-vascular endothelial growth factor injections. Each of these patients had active leaking neovascular AMD in one eye and early ARM or milder disease in the fellow eye. Eyes with neovascular AMD demonstrated lower average levels of DLA compared with their fellow eyes with early ARM (p=0.037, t test). The significant difference in DLA demonstrates the potential of multispectral imaging for differentiating the two pathologies non-invasively. PMID:23137662

  3. Results of Intravitreal Ranibizumab Treatment for Exudative Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Umut Karaca

    2012-01-01

    Full Text Available Pur po se: To evaluate the efficacy and safety of intravitreal ranibizumab injection for exudative age-related macular degeneration. Ma te ri al and Met hod: In this study, we included forty-eight eyes of 43 age-related macular degeneration patients followed for at least twelve months. Mean age was 73.65±8.93 years and mean follow-up time was 14.2 months. All patients received three consecutive monthly intravitreal ranibizumab injections and then were followed up with clinical examination and optic coherence tomography monthly. Re-injection was executed as needed. Re sults: Twenty patients were male (46.5% and twenty-three patients were female (53.5%. The average number of ranibizumab injection was 3.7 (3-7 per eye. Twenty-six lesions (54.2% were classic (predominantly and minimally and twenty-two (45.8% were occult. Mean best-corrected visual acuity was 46.8 letters with ETDRS chart at the initial examination and 55.5 letters at twelfth month. Mean central foveal thickness decreased from 320 microns to 269 microns. There was a statistically significant improvement in visual acuity and central foveal thickness. On the other hand, this improvement was not significant between lesion types. During follow-up, there were no systemic or serious ocular complications determined. Dis cus si on: Intravitreal ranibizumab injection is safe and effective, both anatomically and functionally, for age-related macular degeneration. (Turk J Ophthalmol 2012; 42: 25-9

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

    Science.gov (United States)

    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 25OHDAMD (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. PMID:27105707

  5. Neovascular age-related macular degeneration risk based on CFH, LOC387715/HTRA1, and smoking.

    OpenAIRE

    Hughes, Anne E.; Nick Orr; Chris Patterson; Hossein Esfandiary; Ruth Hogg; Vivienne McConnell; Giuliana Silvestri; Usha Chakravarthy

    2007-01-01

    Editors' Summary Background. Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. The macula is the central region of the retina, the tissue at the back of the eye that converts light into electrical messages and sends them to the brain. In the commonest form of AMD—“dry” AMD—the light-sensitive cells in the macula gradually die. In “wet” or “neovascular” AMD (one in 10 cases of AMD, but responsible for 90% of severe AMD-related blindness), abnormal blood...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One of...... stimulation with TNF-alpha or activated T cells (P<0.01). These findings indicate that PTX3 expressed in the eye cannot be detected systemically and systemic PTX3 may have little or no impact on disease progression, but our findings do not exclude that locally produced PTX3 produced in the posterior segment...

  7. VISUAL REHABILITATION IN LOW VISION PATIENTS WITH AGE-RELATED MACULAR DEGENERATION

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    Using optical visual aids, visual rehabilitation was performed in 14 low vision patients(25 eyes) with age-related macular degeneration. With distance aids, visual acuity improvement appeared in 24 eyes(95%) out of the 25 eyes. Twelve eyes(48%) obtained a visual acuity equal to or better than 0.4. With near visual aids, near acuity of all eyes(100%) was improved. Thirteen eyes(52%) got the near vision equal to or better than 0.5. Ten patients could read No.5 Chinese Reading Card. The reading success rat...

  8. New era for personalized medicine: the diagnosis and management of age-related macular degeneration

    Science.gov (United States)

    Baird, Paul N; Hageman, Gregory S; Franzco, Robyn H Guymer

    2014-01-01

    It can be argued that age-related macular degeneration is one of the best characterized complex trait diseases. Extensive information related to genetic and environmental risk factors exists, and a number of different biological pathways are strongly implicated in its aetiology. Along with recent improvements in high throughput and relatively inexpensive genetic technologies, we are now in a position to consider developing a presymptomatic, personalized approach towards the assessment, management and treatment of this disease. We explore the applicability and challenges of this approach if it is to become commonplace for guiding treatment decisions for individuals with pre-existing disease or for those at high risk of developing it. PMID:19878229

  9. NLRP3 Inflammasome Blockade Inhibits VEGF-A-Induced Age-Related Macular Degeneration

    OpenAIRE

    Alexander G. Marneros

    2013-01-01

    The NLRP3 inflammasome is activated in age-related macular degeneration (AMD), but it remains unknown whether its activation contributes to AMD pathologies. VEGF-A is increased in neovascular (“wet”) AMD, but it is not known whether it plays a role in inflammasome activation, whether an increase of VEGF-A by itself is sufficient to cause neovascular AMD and whether it can contribute to nonexudative (“dry”) AMD that often co-occurs with the neovascular form. Here, it is shown that an increase ...

  10. [The immunomodulatory role of retinal microglial cells in age-related macular degeneration].

    Science.gov (United States)

    Zhang, P F; Sun, X D

    2016-05-11

    Age-related macular degeneration (AMD) is one of the major causes of visual impairment in the elder population. Recent studies have revealed that retinal microgliacytes may play an important role in the pathogenesis of AMD, and the activation of retinal microglia could regulate the progress of AMD. The immunomodulatory role of retinal microglial cells is reviewed in this article, so as to investigate the mechanism and provide new insight for prevention and treatment of AMD.(Chin J Ophthalmol, 2016, 52: 386-390). PMID:27220713

  11. Apolipoprotein E gene and age-related macular degeneration in a Chinese population

    OpenAIRE

    Sun, Erdan; Lim, Apiradee; Liu, Xipu; Snellingen, Torkel; Wang, Ningli; Liu, Ningpu

    2011-01-01

    Purpose To examine the association between apolipoprotein E (APOE) polymorphisms and age-related macular degeneration (AMD) in a Chinese population. Methods The study consisted of 712 subjects, including 201 controls, 363 cases with early AMD, and 148 cases with exudative AMD. Genomic DNA was extracted from venous blood leukocytes. Common allelic variants of APOE (ε2, ε3, and ε4) were analyzed by PCR and direct sequencing. Results APOE ε3ε3 was the most frequent genotype, with a frequency of ...

  12. Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

    Science.gov (United States)

    Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

  13. Aflibercept in wet age-related macular degeneration: a perspective review.

    Science.gov (United States)

    Ohr, Matthew; Kaiser, Peter K

    2012-07-01

    In the treatment of neovascular age-related macular degeneration (AMD), vascular endothelial growth factor (VEGF) has emerged as a key target of therapy. Currently, patients with neovascular AMD are treated with monthly intravitreal injections of anti-VEGF medications. Aflibercept is a novel recombinant fusion protein engineered to bind all isoforms of VEGF-A, VEGF-B, and placental growth factor. It is the latest medication to receive US Federal Drug Administration (FDA) approval for the treatment of neovascular AMD. Theoretical models suggest this molecule may have a longer duration of action compared with current treatments. The results of the VEGF Trap-Eye: Investigation of Efficacy and Safety in wet Age-related Macular Degeneration studies (VIEW 1 and VIEW 2) support this by demonstrating that aflibercept, dosed every 2 months after a monthly loading dose for 3 months, was noninferior in the proportion of patients who maintained or improved vision at 52 weeks compared with monthly injections of ranibizumab. These results were maintained over the 2 years of the studies. Aflibercept (Eylea; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA and Bayer, Basel, Switzerland) was approved by the FDA for the treatment of neovascular AMD on 18 November 2011. PMID:23342231

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

    International Nuclear Information System (INIS)

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

  15. A STUDY TO COMPARE FUNDUS FLUORESCEIN ANGIOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY IN AGE RELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    Rani Sujatha

    2016-02-01

    Full Text Available PURPOSE To compare the diagnostic accuracy of optical coherence tomography with Fundus Fluorescein Angiography in diagnosing Age related macular degeneration. METHODS A total 25 patients newly diagnosed as Age related macular degeneration were included in the study. The study was done during the time period between August 2013 to November 2015 this is a prospective randomized hospital based study. RESULTS Maximum no of patients affected belonged to the age group of 50-70 years and 60% were females. The most common symptom was defective vision accounting for 92%. Hypertension and hyperlipidemia were the most common risk factors. 12% of the cases had unilateral disease and 88% had bilateral disease. 6% of eyes were normal in both FFA and OCT. 62% of the eyes by FFA and 61% of the eyes by OCT had dry ARMD and 32 % of the eye by FFA and 33 % by OCT had wet ARMD. CONCLUSION Fundus Fluorescein Angiography is the gold standard tool for screening ARMD and OCT is more specific in detecting early subretinal neovascular membrane and also to assess the activity of the neovascular membranes. Hence OCT is superior to FFA in diagnosing early wet ARMD and thus helps in early management of patients with ARMD.

  16. Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

  17. Reading performance with various lamps in age-related macular degeneration.

    Science.gov (United States)

    Eperjesi, F; Maiz-Fernandez, C; Bartlett, H E

    2007-01-01

    The purpose of this study was to determine if there was an objective difference in reading between four commonly available lamps, of varying spectral radiance, for 13 subjects with age-related maculopathy (ARM) or non-exudative age-related macular degeneration (AMD)--logMAR visual acuity between 0.04 and 0.68. At a constant illuminance of 2000 lux, there was no interaction between ARM and AMD subgroups and no statistically significant difference between the lamps: standard (clear envelope) incandescent, daylight simulation (blue tint envelope) incandescent, compact fluorescent and halogen incandescent, for any reading outcome measure (threshold print size p = 0.67, critical print size p = 0.74, acuity reserve p = 0.84 and mean reading rate p = 0.78). For lamps typically used in low-vision rehabilitation, a clinically significant effect of spectral radiance on reading for people with ARM or non-exudative AMD is unlikely. PMID:17239195

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

    Directory of Open Access Journals (Sweden)

    Allen Taylor

    2013-07-01

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

  19. Degeneração macular relacionada à idade: novas perspectivas Age-related macular degeneration: new perspectives

    Directory of Open Access Journals (Sweden)

    Marcio Bittar Nehemy

    2006-12-01

    Full Text Available A degeneração macular relacionada à idade (DMRI é a principal causa de cegueira legal em indivíduos acima de 50 anos de idade. Embora estudos recentes tenham mostrado que o fator genético é significativo, a patogênese da degeneração macular relacionada à idade permanece obscura, e os fatores de risco não estão ainda completamente estabelecidos. Estudos multicêntricos randomizados, publicados nos últimos anos, demonstraram que uma combinação de vitaminas e minerais é eficaz na redução do risco de desenvolvimento de neovascularização e de progressão para os estágios mais avançados da degeneração macular relacionada à idade. De maneira análoga, a terapia fotodinâmica (PDT e a terapia antiangiogênica também tiveram sua eficácia comprovada no tratamento de membrana neovascular coroideana subfoveal associada à degeneração macular relacionada à idade. Ambas reduzem o risco de perda de visão e, eventualmente, permitem melhora temporária da acuidade visual. Outras modalidades de tratamento, tais como fotocoagulação a laser, remoção cirúrgica da membrana e termoterapia transpupilar (TTT, podem beneficiar apenas um pequeno subgrupo de pacientes. Uma melhor compreensão dos mecanismos fisiopatológicos e dos eventos moleculares nas diversas fases da doença deverão propiciar, em futuro próximo, melhores estratégias para o controle e tratamento da degeneração macular relacionada à idade.Age-related macular degeneration (ARMD is a major source of legal blindness in individuals older than 50 years. Even though recent reports suggest that genetics plays an important role, its pathogenesis remains puzzling and the risk factors for its occurrence are not completely established. Vitamin and mineral supplementation reduced the risk of development of choroidal neovascularization (CNV or progression to the most advanced stages of age-related macular degeneration. Photodynamic therapy (PDT and antiangiogenic therapy

  20. ALGORITHM OF DIAGNOSTICS AND TREATMENT OF AN AGE-RELATED MACULAR DEGENERATION AT PATIENTS WITH CHRONIC PERIPHERAL UVEITIS

    OpenAIRE

    Yu. I. Khoroshikh; O.I. Krivosheina; Ye. V. Melekhin

    2015-01-01

    The results of clinical trial of various approaches in treatment the exudative forms of macular degenerations, including age-related, against chronic slow intensity inflammatory process on the extreme retinal periphery of an eye are described in represented material. There were 91 patients (105 eyes) in the research with different types of an exudative macular degeneration. The general criteria of inclusion were: age of 18–80 years old, complaints to discomfort in eyes, a spot before an eye, ...

  1. Macular Degeneration Partnership

    Science.gov (United States)

    AMD Macular Degeneration Partnership High Contrast Original + Font Size – Home About AMD Dry AMD Wet AMD Experience AMD Living with ... vision on a daily basis. AMD (Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To ...

  2. Age Related Macular Degeneration and Total Hip Replacement Due to Osteoarthritis or Fracture: Melbourne Collaborative Cohort Study.

    Directory of Open Access Journals (Sweden)

    Elaine W Chong

    Full Text Available Osteoarthritis is the leading cause of total hip replacement, accounting for more than 80% of all total hip replacements. Emerging evidence suggests that osteoarthritis has a chronic inflammatory component to its pathogenesis similar to age-related macular degeneration. We evaluated the association between age-related macular degeneration and total hip replacement as proxy for severe osteoarthritis or fractured neck of femur in the Melbourne Collaborative Cohort Study. 20,744 participants had complete data on both age-related macular degeneration assessed from colour fundus photographs taken during 2003-2007 and total hip replacement. Total hip replacements due to hip osteoarthritis and fractured neck of femur during 2001-2011 were identified by linking the cohort records to the Australian Orthopedic Association National Joint Replacement Registry. Logistic regression was used to examine the association between age-related macular degeneration and risk of total hip replacement due to osteoarthritis and fracture separately, adjusted for confounders. There were 791 cases of total hip replacement for osteoarthritis and 102 cases of total hip replacement due to fractured neck of femur. After adjustment for age, sex, body mass index, smoking, and grouped country of birth, intermediate age-related macular degeneration was directly associated with total hip replacement for osteoarthritis (odds ratio 1.22, 95% CI 1.00-1.49. Late age-related macular degeneration was directly associated with total hip replacement due to fractured neck of femur (odds ratio 5.21, 95% CI2.25-12.02. The association between intermediate age-related macular degeneration and an increased 10-year incidence of total hip replacement due to osteoarthritis suggests the possibility of similar inflammatory processes underlying both chronic diseases. The association of late age-related macular degeneration with an increased 10-year incidence of total hip replacement due to fractured

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

    Science.gov (United States)

    Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

  4. Interaction of complement factor h and fibulin3 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    M Keith Wyatt

    Full Text Available Age-related macular degeneration (AMD is a major cause of vision loss. It is associated with development of characteristic plaque-like deposits (soft drusen in Bruch's membrane basal to the retinal pigment epithelium (RPE. A sequence variant (Y402H in short consensus repeat domain 7 (SCR7 of complement factor H (CFH is associated with risk for "dry" AMD. We asked whether the eye-targeting of this disease might be related to specific interactions of CFH SCR7 with proteins expressed in the aging human RPE/choroid that could contribute to protein deposition in drusen. Yeast 2-hybrid (Y2H screens of a retinal pigment epithelium/choroid library derived from aged donors using CFH SCR7 baits detected an interaction with EFEMP1/Fibulin 3 (Fib3, which is the locus for an inherited macular degeneration and also accumulates basal to macular RPE in AMD. The CFH/Fib3 interaction was validated by co-immunoprecipitation of native proteins. Quantitative Y2H and ELISA assays with different recombinant protein constructs both demonstrated higher affinity for Fib3 for the disease-related CFH 402H variant. Immuno-labeling revealed colocalization of CFH and Fib3 in globular deposits within cholesterol-rich domains in soft drusen in two AMD donors homozygous for CFH 402H (H/H. This pattern of labeling was quite distinct from those seen in examples of eyes with Y/Y and H/Y genotypes. The CFH 402H/Fib3 interaction could contribute to the development of pathological aggregates in soft drusen in some patients and as such might provide a target for therapeutic intervention in some forms of AMD.

  5. Transpupillary thermotherapy for choroidal neovascular membrane in age related macular degeneration

    Directory of Open Access Journals (Sweden)

    Agarwal Manisha

    2004-01-01

    Full Text Available Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT in choroidal neovasularisation (CNVM secondary to age related macular degeneration ( AMD. Material and methods: Retrospective, non-randomized study of 28 eyes of 28 patients with subfoveal CNVM (classic, occult or mixed secondary to AMD. Results: Fifteen patients (53.57% maintained their pre-treatment vision, 2 (7.14% patients showed improvement of more than 2 lines and 11(39.28% patients showed deterioration of vision by> 2 lines. Angiographic and clinical regression of CNVM was noted in 19 patients (67.8% on an average follow up of 15.32 ± 3.31 months. Conclusion: TTT leads to stabilisation of vision in 60% of treated eyes with CNVM due to AMD.

  6. Influence of optical radiations on development of age related macular degeneration (AMD)

    International Nuclear Information System (INIS)

    It is known that millions of people have impaired vision because of age-related macular degeneration (AMD). Our goal was to study possible association of ultraviolet radiation with the development of AMD. Clinical examination was carried out on small island of Rab in Croatia with a high UV-index in the summer, ranging from 9 to 11 around noon. Subjects were classified in two groups, the first consisting of farmers and fishermen and the second of urban population. Fundus analysis showed AMD in 16% of people from the first group and only in 2% of people in the second group. Pseudoexfoliation syndrome was found in 10% of subjects from the first group and only in 1% of subjects from the second group. In the first group, temporary AMD was observed in young people, aged between 40 and 45 years. (author)

  7. The Role of Inflammation in the Pathogenesis of Age-related Macular Degeneration

    Science.gov (United States)

    Donoso, Larry A.; Kim, David; Frost, Arcilee; Callahan, Alston; Hageman, Gregory

    2014-01-01

    Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is a complex disease to study because of the potential role of demographic, environmental, and other systemic risk factors, such as age, sex, race, light exposure, diet, smoking, and underlying cardiovascular disease which may contribute to the pathogenesis of this disease. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement Factor H gene, have been found to be strongly associated with the development of AMD in Caucasians. One single nucleotide polymorphism, Tyr402His, was associated with approximately 50% of AMD cases. We review recent developments in the molecular biology of AMD, including single nucleotide polymorphisms within the Factor H gene, which may predispose individuals to the susceptibility of AMD as well as single nucleotide polymorphisms that may confer a protective effect. Taken together these findings help to provide new insights into the central issues surrounding the pathogenesis of AMD. PMID:16500214

  8. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled...... neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks, 3...... months and 6 months after the first injection. Re-treatment was given on an 'as needed' basis. Results: Twenty-four eyes of 24 patients completed 6 months of follow-up. Two patients chose to discontinue the study. Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (P < 0...

  9. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Zhenglin Yang

    2010-02-01

    Full Text Available A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

  10. The value of radiotherapy in the treatment of aged-related macular degeneration (AMD)

    International Nuclear Information System (INIS)

    Age-related macular degeneration (AMD) is the leading cause of blindness in patients older then 65 years. There are two forms of AMD: exudative wet and nonexudative dry. Most of the lesions are not amenable to laser therapy because of their vicinity to the fovea. Earlier studies suggested that radiotherapy may inhibit further loss of visual acuity but following studies rendered contradictory results. In recent years, treatment of benign disease has again attracted the interest of the radiation oncology community in the Western part of the world. Radiotherapy has been given successfully to patients suffering from a wide variety diseases and AMD is one of them. The present article extensively reviews the clinical studies to define the role of radiotherapy in the treatment of AMD. (authors)

  11. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara Brandi; Fuchs, Josefine; Hansen, Louise Kim Hillerup; Lund-Andersen, Henrik; Sander, Birgit; Larsen, Michael

    2015-01-01

    PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included...... 1185 eyes in 1099 patients who began vascular endothelial growth factor inhibitor treatment for nAMD during four separate periods in 2007, 2009, 2011 and 2012 using a fixed loading-dose regimen of three ranibizumab injections. RESULTS: Mean best-corrected visual acuity (BCVA) at presentation remained...... median time to treatment from 16 days to 1 day. The proportion of patients with fellow-eye BCVA 0.05 or worse at presentation with newly diagnosed wet AMD in the incident eye decreased from 38% to 22% (p < 0.0018). The proportion of bilaterally treated patients increased during the study period...

  12. Bevacizumab (Avastin) conjugated microbubbles for anti-VEGF treatment of neovascular age-related macular degeneration

    Science.gov (United States)

    Zhang, Leilei; Xu, Jeff; Huang, Jiwei; Roberts, Cynthia; Xu, Ronald

    2010-02-01

    Bevacizumab (Avastin) has been used as one of the anti-VEGF therapies to manage neovascular age-related macular degeneration (AMD). The drug delivery system for bevacizumab needs to be improved in order to decrease the frequency of injection and reduce the adverse effects. In our study, bevacizumab was conjugated with poly (lactic-co-glycolic acid) (PLGA) microbubbles by activating carboxyl functional groups. The averaged size of microbubbles was estimated 1.055+/-0.258μm, allowing for ultrasound guided drug delivery. The binding efficiency between bevacizumab and microbubbles was evaluated in an enzyme-linked immunosorbent assay plate. The test results demonstrated the potential of using PLGA microbubbles to deliver bevacizumab with imaging guidance.

  13. The Use of Intravitreal Aflibercept in the Treatment of Wet Type of Age Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Rejith Rag

    2015-04-01

    Full Text Available Aflibercept, an anti vascular endothelial growth factor (anti-VEGF which was originally developed in the treatment of large bowel cancers, has been found to be effective in the treatment of wet type of age related macular degeneration (ARMD, a potentially sight threatening condition affecting the retina. Chemically this biological drug is C4318 H6788 N1164 O1304 S12 with a molecular weight of 96.9 KDa. This is manufactured as a lipid soluble recombinant fusion glycoprotein that binds with both forms of vascular endothelial growth factors, i.e. A and B as well as placental growth factors, thus blocking the angiogenic action and consequent neovascular membrane growth, the pathognomonic feature of wet ARMD.

  14. Radiation therapy for wet type age-related macular degeneration. Long term follow-up results

    International Nuclear Information System (INIS)

    Between April, 1994 and July, 1995, 33 patients with occult type choroidal neovascularization (CNV) with or without the classical type CNV of the wet type age-related macular degeneration ARMD were treated with radiation therapy (10 Gy/5 fx/1 week or 20 Gy/10 fx/2 weeks). This phase I/II study showed that radiation therapy seems to be useful for CNV during the first 12 months. Some eyes which initially showed good response to irradiation began to lose their visual acuity. However, the dose of 20 Gy in 10 fractions seemed useful to maintain the visual acuity better than 0.1 in this long term follow-up study (24 months). (author)

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

    DEFF Research Database (Denmark)

    Kessel, Line; Erngaard, Ditte; Flesner, Per; Andresen, Jens; Tendal, Britta; Hjortdal, Jesper

    2015-01-01

    PURPOSE: Age-related macular degeneration (AMD) and cataract often coexist in patients and concerns that cataract surgery is associated with an increased risk of incidence or progression of existing AMD has been raised. This systematic review and meta-analysis is focused on presenting the evidence...... concerning progression of AMD in patients undergoing cataract surgery. METHODS: We performed a systematic literature search in the PubMed, Medline, Cochrane Library and CINAHL databases. Two randomized trials and two case-control trials were identified. Quality of the studies was assessed using the Cochrane...... risk of bias tool, data were extracted, and meta-analyses were performed. Quality of the available evidence was evaluated using the GRADE system. RESULTS: We found that visual acuity at 6-12 months follow-up was significantly better (6.5-7.5 letters) in eyes that had undergone cataract surgery than in...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were...... recruited from our outpatient retinal clinic. Control individuals were typically spouses. The diagnosis of neovascular AMD was confirmed using fluorescein and indocyaningreen angiography. Fresh venous blood was analyzed by flow cytometry using fluorochrome-conjugated antibodies to the Treg surface antigens...... CD4, CD25, CD127, CD45RA, and CD31. Main outcome measures were the percentage of CD25(high)CD127(low) Tregs, the percentage of CD45RA(+) naïve Tregs, and the percentage of CD31(+) recent thymic emigrant Tregs. RESULTS: Comparing patients with neovascular AMD to controls, no significant differences...

  17. Hypersensitivity toward bacterial stimuli in patients with age-related macular degeneration.

    Science.gov (United States)

    Chen, Jia-Jia; Han, Bing-Sha; Xu, Shao-Gang; Vu, Honghua; Farrow, James W; Rodman, Connie L; Zhu, Yu; Wang, Wen-Zhan

    2016-05-01

    Although the pathogenesis of age-related macular degeneration (AMD) is unclear, genetic screening has revealed that polymorphisms in the complement system may be associated with AMD development. Production of autoantibodies was also found in AMD patients. In this study, we analyzed the antibody response in AMD patients. We found that purified B cells from AMD patients tended to respond to lower concentrations of bacterial antigen stimulation, and produced higher amounts of antibodies, especially in IgM and IgA secretions. When examining clinical symptoms, patients with more severe wet-form AMD tended to exhibit higher sensitivity to bacterial antigens and secreted more IgM and IgA antibodies than those with less severe dry-form cases. In conclusion, our study discovered an altered B-cell antibody production in response to bacterial antigens in AMD patients, which potentially contributes to AMD pathogenesis. PMID:26853231

  18. CYTOKINES IN LACRIMAL FLUID AND BLOOD SERUM: EARLY BIOMARKERS OF AGE-RELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    O. S. Slepova

    2015-06-01

    Full Text Available The article presents results of multiplex cytokine assays in blood serum and lacrimal fluid at the initial and intermediate stages of age-related macular degeneration (AMD. Some features of local and systemic disturbances in the cytokine profile were detected in these patients. It was revealed that the initial stage of AMD was associated with elevated IL-17 levels in lacrimal fluid, along with imbalance between the local increase and systemic decrease of TGF-β1 amounts. Intermediate-stage AMD was associated with increased levels of the most cytokines assayed (except of TGF-β1 in blood serum and lacrimal fluid, thus suggesting stimulation of both pro-inflammatory and angiogenic responses, like as activation of anti-inflammatory and anti-infective factors. 

  19. Role of radiotherapy in age-related macular degeneration. A prospective study

    International Nuclear Information System (INIS)

    Aim: To determine the effect of external beam radiotherapy on subfoveal choroidal neovascularization in age-related macular degeneration. Patients and methods: Between September 1995 and July 1996, 40 patients (9 males and 31 females; mean age 74 years, range 61 to 83 years) were included in a prospective study. Eight patients had classic, well defined neovascularisations, 32 patients had occult lesions. Complete ophthalmic investigations included visual acuity contrast sensitivity as well as fluorescein and indocyanine green angiographic examinations prior to treatment and 1, 3, 6, and 12 months after radiotherapy. External beam radiotherapy (8-MV photons) was delivered with a total dose of 14.4 Gy in 8 fractions of 1.8 Gy per day. The field size averaged 5.5x4.5 cm. Results: No treatment related morbidity during or after treatment was obtained. After 6 months follow-up the visual acuity was improved in 2 (5%) patients and maintained at pretreatment level in 17 (42%) patients. However, 12 months post treatment a stable situation was found in 6 (15%) patients and a decrease in visual acuity in 34 (85%) patients. The central visual fields deteriorated significantly from 16.5 decibel (dB) to 12.4 dB. The enlargement of exsudats and neovascular membranes increased 5- to 7-fold. At 12 months after treatment, 3 (7.5%) patients stated that they had improved vision subjectively, 12 (30%) patients had no change and 25 (62.5%) patients suffered from subjective decrease in visual acuity. Conclusions: Using a total dose of 14.4 Gy/1.8 Gy no difference concerning visual acuity and exsudative changes in comparison to the natural history on age-related macular degeneration was obtained after 12 months. However, the results of multicenter studies are to be awaited. (orig.)

  20. Physics of Lipofuscin Formation and Growth in Age Related Macular Degeneration

    Science.gov (United States)

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

    2010-02-01

    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). With time, incompletely degraded membrane material builds up in the RPE 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. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results to the number of lipofuscin granules in eyes with early age-related degeneration. )

  1. Current and emerging therapies for the treatment of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    M Vaughn Emerson

    2008-06-01

    Full Text Available M Vaughn Emerson, Andreas K LauerCasey Eye Institute, Oregon Health and Science University, Portland, OR, USAAbstract: Age-related macular degeneration (AMD is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary

  2. Contribution of the Nurses’ Health Study to the Epidemiology of Cataract, Age-Related Macular Degeneration, and Glaucoma

    Science.gov (United States)

    Wu, Juan; Cho, Eunyoung; Ogata, Soshiro; Jacques, Paul; Taylor, Allen; Chiu, Chung-Jung; Wiggs, Janey L.; Seddon, Johanna M.; Hankinson, Susan E.; Schaumberg, Debra A.; Pasquale, Louis R.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) to understanding the genetic and lifestyle factors that influence the risk of cataract, age-related macular degeneration, and glaucoma. Methods. We performed a narrative review of the publications of the NHS between 1976 and 2016. Results. The NHS has helped to elucidate the roles of genetics, lifestyle factors (e.g., cigarette smoking associated with cataract extraction and age-related macular degeneration), medical conditions (e.g., diabetes associated with cataract extraction and glaucoma), and dietary factors (e.g., greater carotenoid intake and lower glycemic diet associated with lower risk of age-related macular degeneration) in the etiology of degree and progression of lens opacities, cataract extraction, age-related macular degeneration, primary open-angle glaucoma, and exfoliation glaucoma. Conclusions. The findings from the NHS, combined with those of other studies, have provided compelling evidence to support public health recommendations for helping to prevent age-related eye diseases: abstinence from cigarette smoking, maintenance of healthy weight and diabetes prevention, and a healthy diet rich in fruits and vegetables. PMID:27459452

  3. 6-weekly bevacizumab versus 4-weekly ranibizumab for neovascular age-related macular degeneration: a 2-year outcome

    OpenAIRE

    Patrick J Chiam; Vivian W Ho; Nicholas M Hickley; Venkat Kotamarthi

    2016-01-01

    AIM: To compare visual acuity and central macular thickness (CMT) changes in neovascular age related macular degeneration patients treated with either 6 weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis. METHODS: Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits. Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on th...

  4. Age-Related Macular Degeneration: New Eye Treatment Saves Former Math Teacher's Sight

    Science.gov (United States)

    ... related Macular Degeneration New Eye Treatment Saves Former Math Teacher's Sight Summer 2016 Table of Contents Rebecca ... Courtesy of: Rebecca Hatcher Rebecca Hatcher, a retired math teacher from Virginia, is an example of the ...

  5. Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.

    Science.gov (United States)

    Wei, Cynthia X; Sun, Aixu; Yu, Ying; Liu, Qianyong; Tan, Yue-Qing; Tachibana, Isamu; Zeng, Hong; Wei, Ji-Ye

    2016-01-01

    Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD. PMID:26427400

  6. The molecular genetic basis of age-related macular degeneration: an overview

    Indian Academy of Sciences (India)

    Saritha Katta; Inderjeet Kaur; Subhabrata Chakrabarti

    2009-12-01

    Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly. While the prevalence is relatively higher in the Caucasian populations, it has gradually become a major public health issue among the non-Caucasian populations (including Indians) as well due to senescence, rapidly changing demographics and life-style factors. Recent genome-wide association studies (GWAS) on large case–control cohorts have helped in mapping genes in the complement cascade that are involved in the regulation of innate immunity with AMD susceptibility. Genes involved with mitochondrial oxidative stress and extracellular matrix regulation also play a role in AMD pathogenesis. Majority of the associations observed in complement (CFH, CFB, C2 and C3) and other (ARMS2 and HTRA1) genes have been replicated in diverse populations worldwide. Gene–gene (CFH with ARMS2 and HTRA1) interactions and correlations with environmental traits (smoking and body mass index) have been established as significant covariates in AMD pathology. In this review, we have provided an overview on the underlying molecular genetic mechanisms in AMD worldwide and highlight the AMD-associated-candidate genes and their potential role in disease pathogenesis.

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

    Directory of Open Access Journals (Sweden)

    Ricardo Casaroli-Marano

    2014-01-01

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

  8. Clinical outcomes of the treatment of exudative age-related macular degeneration with Pegaptanib

    Directory of Open Access Journals (Sweden)

    M. Burova

    2013-02-01

    Full Text Available ABSTRACT Purpose. To evaluate the results of intravitreal use of Pegaptanib in patients with exudative age-related macular degeneration (AMD. Material end methods. Our study includes 77 patients with exudative AMD, who received 9 injections of Pegaptanib 0.3mg with 6-weeks intervals between them. So the primary treatment lasted one year. During and after the treatment these patients underwent fluorescent angiography (FAG, optical coherence tomography (OCT, fundus photography and best corrected visual acuity (BCVA examination. According to the results of these examinations a decision about a further treatment, whether it was necessary, was taken. Results. By the end of our 2-year study 38 patients after therapy with Pegaptanib had complete obliteration of the choroidal neovascularization (CNV, 19 patients were switched to Ranibizumab, one patient underwent photodynamic therapy with Visudyne, 14 patients had severe progression of AMD, when there was no sense in further treatment, 2 patients dropped out the study because of cerebral insult, 3 patients refused of any further treatment, in spite of persisting exudative activity of the CNV after the primary treatment. Conclusion. Intravitreal аpplication of Pegaptanib is a relatively effective treatment option of exudative AMD as BCVA was stabilized or improved in 55.8% of patients, macular edema decreased in 67.5% of patients and neovascular membrane was obliterated in 49.35% of patients.

  9. Analysis of rare variants in the C3 gene in patients with age-related macular degeneration

    NARCIS (Netherlands)

    M.R. Duvvari (Maheswara); C.C. Paun (Codrut); G.H.S. Buitendijk (Gabrielle); N.T.M. Saksens (Nicole T.); E.B. Volokhina (Elena); T. Ristau (Tina); F.E. Schoenmaker-Koller (Frederieke); J.P.H. van de Ven (Johannes P.); J.M.M. Groenewoud (Joannes); L.P. van den Heuvel (Lambert); A. Hofman (Albert); B.C.J.M. Fauser (Bart); A.G. Uitterlinden (André); C.C.W. Klaver (Caroline); C. Hoyng (Carel); E.K. de Jong (Eiko); A.I. Hollander (Anneke)

    2014-01-01

    textabstractAge-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missi

  10. Analysis of rare variants in the C3 gene in patients with age-related macular degeneration

    NARCIS (Netherlands)

    Duvvari, M.R.; Paun, C.C.; Buitendijk, G.H.; Saksens, N.T.M.; Volokhina, E.B.; Ristau, T.; Schoenmaker-Koller, F.E.; Ven, J.P.H. van de; Groenewoud, J.M.M.; Heuvel, L.P.W.J. van den; Hofman, A.; Fauser, S.; Uitterlinden, A.G.; Klaver, C.C.; Hoyng, C.B.; Jong, E.K.; Hollander, A.I. den

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritabil

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

    Science.gov (United States)

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

  12. Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; la Cour, Morten; Sander, Birgit; Hansen, Louise K H; Fuchs, Josefine; Lund-Andersen, Henrik; Larsen, Michael

    2013-01-01

    Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria...

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

    Directory of Open Access Journals (Sweden)

    A. V. Kolesnikov

    2014-07-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten; Nissen, Mogens H; Hviid, Thomas; Sørensen, Torben Lykke

    2014-01-01

    Purpose: The chemokine receptor CXCR3 has been strongly related to inhibition of angiogenesis. The purpose of this study was to investigate the association between expression of CXCR3 on peripheral blood leukocytes and Age-related Wet Macular Degeneration (AMD). Furthermore, we measured the plasma...

  16. Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration.

    NARCIS (Netherlands)

    Smailhodzic, D.; Klaver, C.C.; Klevering, B.J.; Boon, C.J.F.; Groenewoud, J.M.M.; Kirchhof, B.; Daha, M.R.; Hollander, A.I. den; Hoyng, C.B.

    2012-01-01

    PURPOSE: Systemic complement activation is associated with age-related macular degeneration (AMD) and has mainly been attributed to a risk allele in the complement factor H (CFH) gene. Whether other important AMD genes also influence complement activation is unclear. In the present case-control stud

  17. Face recognition in age related macular degeneration: perceived disability, measured disability, and performance with a bioptic device

    OpenAIRE

    Tejeria, L; Harper, R A; Artes, P H; Dickinson, C M

    2002-01-01

    Aims: (1) To explore the relation between performance on tasks of familiar face recognition (FFR) and face expression difference discrimination (FED) with both perceived disability in face recognition and clinical measures of visual function in subjects with age related macular degeneration (AMD). (2) To quantify the gain in performance for face recognition tasks when subjects use a bioptic telescopic low vision device.

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

    Science.gov (United States)

    Warren, Mary

    2008-01-01

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

  19. The Difference that Age Makes: Cultural Factors that Shape Older Adults' Responses to Age-Related Macular Degeneration

    Science.gov (United States)

    Mogk, Marja

    2008-01-01

    This article suggests that approaching vision loss from age-related macular degeneration from a sociocultural perspective, specifically considering perceptions of aging, blindness, disability, and generational viewpoints and norms, may be critical to understanding older adults' responses to vision loss and visual rehabilitation.

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

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten; Nissen, Mogens Holst; Hviid, Thomas; Sørensen, Torben Lykke

    2014-01-01

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

  1. In patients with neovascular age-related macular degeneration, physical activity may influence C-reactive protein levels

    DEFF Research Database (Denmark)

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

    2014-01-01

    Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated...... the impact of physical activity on CRP levels in patients with neovascular AMD and control individuals....

  2. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model.

    Science.gov (United States)

    Ardeljan, Christopher P; Ardeljan, Daniel; Abu-Asab, Mones; Chan, Chi-Chao

    2014-01-01

    The etiology of Age-related Macular Degeneration (AMD) remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope-particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death. PMID:25580276

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

    Directory of Open Access Journals (Sweden)

    Jiangyuan Gao

    2015-01-01

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

  4. What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD)?

    OpenAIRE

    Bockelbrink, A; Rasch, A; Roll, S.; Willich, SN; Greiner, W

    2006-01-01

    Background The cataract (Cataracta senilis) is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology - can be seen as routine surgery. The age related macular degeneration (AMD) is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing ...

  5. What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD)?

    OpenAIRE

    Willich, Stefan N.; Roll, Stephanie; Rasch, Andrej; Bockelbrink, Angelina; Greiner, Wolfgang

    2006-01-01

    Background: The cataract (Cataracta senilis) is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD) is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing...

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

    DEFF Research Database (Denmark)

    Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I; Sperling, Marvin; Klamerus, Karen J; Chi-Burris, Katherine; Yan, Eric; Paggiarino, Dario A; Rosenblatt, Irit; Aitchison, Roger; Erlich, Shai S; Larsen, Michael

    2012-01-01

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

  7. Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

    Directory of Open Access Journals (Sweden)

    Paul Mitchell

    Full Text Available Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%. Ranibizumab given as needed would reduce incident blindness by 68% (64-71%. Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39% with monthly intravitreal ranibizumab, and by 28% (23-33% with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

  8. Visual outcome of intravitreal ranibizumab for exudative age-related macular degeneration: timing and prognosis

    Directory of Open Access Journals (Sweden)

    Canan H

    2014-01-01

    Full Text Available Handan Canan,1 Selçuk Sizmaz,2 Rana Altan-Yaycioğlu,1 Çağla Saritürk,3 Gürsel Yilmaz41Department of Ophthalmology, Adana Teaching and Medical Research Center, Baskent University School of Medicine, 2Department of Ophthalmology, Çukurova University School of Medicine, 3Department of Biostatistics, Adana Teaching and Medical Research Center, Baskent University School of Medicine, 4Department of Ophthalmology, Baskent University School of Medicine, Ankara, TurkeyPurpose: To describe 1-year clinical results of intravitreal ranibizumab treatment in patients with choroidal neovascularization secondary to exudative age-related macular degeneration (AMD and to evaluate whether early treatment is a predictive value for prognosis of the disease.Materials and methods: Clinical records were retrospectively reviewed of 104 eyes that underwent intravitreal ranibizumab therapy for exudative AMD. Patients were divided into two groups according to their symptom duration: group 1, <1 month; and group 2, 1–3 months. After three monthly injections, patients were examined monthly, and subsequent injections were performed as needed.Results: There were 43 female (48.9% and 45 males (51.1%. The follow-up time was 13.7±1.9 (12–19 months. The mean logarithm of minimum angle of resolution best-corrected visual acuity (BCVA improved significantly, from 0.45±0.639 at baseline to 0.08±0.267 at 12 months in group 1, and from 1.06±0.687 at baseline to 0.75±0.563 at 12 months in group 2. The increase in BCVA was statistically significant in group 1 (P=0.009. The mean central retinal thickness (CRT decreased significantly, from 355.13±119.93 µm at baseline to 250.85±45.48 µm at 12 months in group 1, and from 371.88±91.047 µm at baseline to 268.61±53.51 µm at 12 months in group 2. The decrease in CRT was statistically significant in group 1 (P=0.001.Conclusion: Intravitreal ranibizumab therapy was effective in significantly increasing mean BVCA and

  9. Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration

    Directory of Open Access Journals (Sweden)

    Keles S

    2014-08-01

    Full Text Available Sadullah Keles,1 Orhan Ates,1 Baki Kartal,2 Hamit Hakan Alp,3 Metin Ekinci,4 Erdinc Ceylan,2 Osman Ondas,5 Eren Arpali,2 Semih Dogan,6 Kenan Yildirim,7 Mevlut Sait Keles8 1Department of Ophthalmology, School of Medicine, Ataturk University, Erzurum, Turkey; 2Department of Ophthalmology, Regional Training and Research Hospital, Erzurum, Turkey; 3Department of Biochemistry, School of Medicine, Yuzuncu Yil University, Van, Turkey; 4Department of Ophthalmology, School of Medicine, Kafkas University, Kars, Turkey; 5Department of Ophthalmology, Erbaa Government Hospital, Tokat, Turkey; 6Department of Ophthalmology, Kolan Hospital, Istanbul, Turkey; 7Department of Ophthalmology, Igdir Government Hospital, Igdir, Turkey; 8Department of Biochemistry, School of Medicine, Ataturk University, Erzurum, Turkey Aim: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA, and nitric oxide (NO, as well as activity of endothelial NO synthase (eNOS, in patients with age-related macular degeneration (AMD.Methods: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30 were compared to a control group with no retinal pathology (n=30.Results: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001, whereas NO levels and eNOS activity were higher in the control group (P<0.001. In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively.Conclusion: Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD. Keywords: age-related macular

  10. Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany

    Directory of Open Access Journals (Sweden)

    Nikolaus Feucht

    2008-06-01

    Full Text Available Nikolaus Feucht, Huebner Matthias, Chris P Lohmann, Mathias MaierAugenklinik rechts der Isar, Technical University Munich, GermanyBackground: The VEGF Inhibition Study In Ocular Neovascularisation (VISION reported the efficacy of intravitreal (ITV vascular endothelial growth factor (VEGF inhibition with pegaptanib sodium (Macugen® for the treatment of neovascular age-related macular degeneration (AMD. This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV due to AMD.Material and methods: The study included 50 eyes (in 49 patients with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT. Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT examinations were carried out and intraocular pressure (IOP and visual acuity (VA were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.Results: ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT during the course of the study, from 251.19 µm at baseline to 251.63 µm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.Conclusions: ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good

  11. Lower cognitive function in patients with age-related macular degeneration: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhou LX

    2016-02-01

    Full Text Available Li-Xiao Zhou,1 Cheng-Lin Sun,1 Li-Juan Wei,1 Zhi-Min Gu,1 Liang Lv,1 Yalong Dang21Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, 2Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaObjective: To investigate the cognitive impairment in patients with age-related macular degeneration (AMD.Methods: Relevant articles were identified through a search of the following electronic databases through October 2015, without language restriction: 1 PubMed; 2 the Cochrane Library; 3 EMBASE; 4 ScienceDirect. Meta-analysis was conducted using STATA 12.0 software. Standardized mean differences with corresponding 95% confidence intervals were calculated. All of the included studies met the following four criteria: 1 the study design was a case–control or randomized controlled trial (RCT study; 2 the study investigated cognitive function in the patient with AMD; 3 the diagnoses of AMD must be provided; 4 there were sufficient scores data to extract for evaluating cognitive function between cases and controls. The Newcastle–Ottawa Scale criteria were used to assess the methodological quality of the studies.Results: Of the initial 278 literatures, only six case–control and one RCT studies met all of the inclusion criteria. A total of 794 AMD patients and 1,227 controls were included in this study. Five studies were performed with mini-mental state examination (MMSE, two studies with animal fluency, two studies with trail making test (TMT-A and -B, one study with Mini-Cog. Results of the meta-analysis revealed lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test (P≤0.001 for all. The results also showed that differences in the TMT-A (except AMD [total] vs controls and TMT-B test had no statistical significance (P>0.01. The Newcastle–Ottawa Scale score was ≥5 for all of the included studies. Based on the

  12. Strontium-90 brachytherapy for exudative, age related macular degeneration: a pilot study

    International Nuclear Information System (INIS)

    ARMD is the leading cause of visual loss in the 55 and older population. Recent data suggests that low dose external beam irradiation seems to have a beneficial effect in stabilizing the central visual acuity, by arresting or delaying the progression of the central scotoma. The authors decided to use a newly designed Strontium-90 Macular Applicator in a pilot study to ascertain its effectiveness in controlling exudative, age related macular degeneration. Two groups of 10 patients each were treated. The first group received a total dose of 10 Gy at 1.5 mm depth in a total time of 4 minutes and 20 seconds, fractionated in 4 applications of 1 minute and 5 seconds with 1 minute rest in between to allow blood perfusion. The second group was treated with 15 Gy at the same depth of 1.5 mm in a total time of 6 minutes, in 5 fractions of 1 minute and 20 seconds and 1 minute rest. The first group of patients had a mean follow-up time of 6.7 months, the visual acuity improved at least two Snellen gradations in one eye (10%), stabilized in six eyes (60%) and worsened in three eyes (30%). Among the nine eyes with fluorescein angiographic documentation at four and six months post treatment, the choroidal neovascular membrane remained stable in eight eyes (85%). Strontium-90 brachytherapy appears to be an effective treatment for stabilizing the extent of choroidal neovascular membrane growth on a short term basis. Whether this therapy stabilizes or improves visual acuity, as compared to the natural history of the untreated disease, remains uncertain. The second group will complete six months follow-up soon and the results will be discussed at the time of this presentation

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

    Directory of Open Access Journals (Sweden)

    Michael B. Gorin

    2014-11-01

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

  14. Prevalence of depression and its effect on disability in patients with age-related macular degeneration

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    Banerjee Anindya

    2008-01-01

    Full Text Available Aims: To estimate depression in patients with age-related macular degeneration (AMD and study the relationships among depression, visual acuity, and disability. Materials and Methods: It was a cross-sectional study with consecutive sampling (n = 53 of patients with AMD aged 50 years and above attending the retina clinic of a tertiary care hospital in North India. Depression, general disability and vision-specific disability were assessed in subjects meeting selection criteria. Assessments were done using the fourth edition of Diagnostic and Statistical Manual of mental disorders (DSM- IV Geriatric Depression Scale (GDS, Structured Clinical Interview for DSM-IV Axis -I Disorders, Clinical Version (SCID-CV, World Health Organization Disability Assessment Schedule-II (WHODAS-II and Daily Living Tasks dependent on Vision scale (DLTV. Non-parametric correlation analyses and regression analyses were performed. Results: Out of 53 participants, 26.4% (n = 14 met DSM-IV criteria for the diagnosis of depressive disorder. Depressed patients had significantly greater levels of general and vision-specific disability than non-depressed patients. General disability was predicted better by depression and vision-specific disability than by visual acuity. Conclusion: Depression is a major concern in patients with AMD and contributes more to disability than visual impairment.

  15. Serum VEGF and CFH in Exudative Age-Related Macular Degeneration

    Science.gov (United States)

    Haas, Paulina; Steindl, Kerstin; Aggermann, Tina; Schmid-Kubista, Katharina; Krugluger, Walter; Hageman, Gregory S.; Binder, Susanne

    2014-01-01

    Purpose To determine serum vascular endothelial growth factor 165 (VEGF165) levels and the association of the complement factor H gene (CFH) Y402H polymorphism in patients with exudative age-related macular degeneration (AMD) in comparison to unaffected control subjects. Methods Sixty-six AMD patients and 66 healthy age- and gender-matched controls were included in this case-control study. The serum VEGF165 was assayed by ELISA (R&D). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Chisquared tests were used regarding the polymorphism, a t-test regarding the VEGF-levels. Results Levels of serum VEGF165 were similar in both groups (p-value = 0.2112). Genotype frequency differed significantly between patients with exudative AMD and the healthy control group (p = 0.003136). The serum VEGF165 levels were similar irrespective of the presence of the CFH Y402H polymorphism (p = 0.4113) and independent of the specific genotype (p = 0.9634). Conclusion In the present study exudative AMD is not associated to serum VEGF165 levels; furthermore, our data does not establish a statistical link between VEGF165 and the CFH Y402H polymorphism. PMID:21158586

  16. The past, present, and future of exudative age-related macular degeneration treatment

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    Yoreh Barak

    2012-01-01

    Full Text Available Treatment of exudative age-related macular degeneration has been revolutionized within the last 6 years with the introduction of vascular endothelial growth factor neutralizing agents. Previously popular "destructive treatments," such as laser photocoagulation and photodynamic treatment have either been abandoned or used as an adjunct to pharmacotherapy. Despite the increase in vision after antivascular endothelial growth factor (VEGF agents, they require repetitive and costly intravitreal injections that also carry the inherit risks of infection, retinal tears, and detachment. Several new and more potent VEGF inhibitors are at different stages of development. The goal of evolving pharmacotherapy is to preserve the therapeutic effect while reducing or eliminating the discomfort of intravitreal drug delivery, as well as identify new therapeutic targets. Complement inhibitors, immunomodulators, integrin inhibitors are a few of the new class of drugs that are expected to be in our armamentarium soon. Current medications act to decrease leakage through abnormal subretinal choroidal vasculature and promote involution. However, these medications are only effective in treating the active stage of the choroidal neovascular membrane. Restoration of vision of a large number of patients with involuted choroidal neovascular membranes is warranted. For this purpose, tissue engineering techniques have been employed to reconstruct the subretinal anatomy. Discovery of biomarkers, pharmacogenetics, and very specific targeting holds the promise of increased potency and safety in the future.

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

    Science.gov (United States)

    Li, Jin; Lin, Houwen

    2016-01-01

    Purpose. To assess the cost-effectiveness of bevacizumab compared to ranibizumab, verteporfin photodynamic therapy (PDT), and usual care for the treatment of age-related macular degeneration (AMD) in China. Methods. A Markov model was developed according to patient visual acuity (VA) in the better-seeing eye (Snellen scale). Four cohorts of patients were treated with one of the following therapies: bevacizumab, ranibizumab, PDT, or usual care. Clinical data related to treatments were obtained from published randomized clinical trials. Direct medical costs and resource utilization in the Chinese health care setting were taken into account. Health and economic outcomes were evaluated over a lifetime horizon. Sensitivity analyses were performed. Results. Treatment with ranibizumab provided the greatest gains in quality-adjusted life-years (QALYs). The cost per marginal QALY gained with bevacizumab over usual care was $1,258, $3,803, and $2,066 for the predominantly classic, minimally classic, and occult lesions, respectively. One-way sensitivity analysis showed considerably influential factors, such as utility values and effectiveness data. Probabilistic sensitivity analysis indicated that, compared to usual care, PDT and ranibizumab most cases would be cost-effective in the bevacizumab arm at a threshold of $7,480/QALY. Conclusion. Bevacizumab can be a cost-effective option for the treatment of AMD in the Chinese setting. PMID:27200183

  18. Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

    Science.gov (United States)

    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.

  19. Caregiver perceptions about the impact of caring for patients with wet age-related macular degeneration.

    Science.gov (United States)

    Vukicevic, M; Heraghty, J; Cummins, R; Gopinath, B; Mitchell, P

    2016-03-01

    PurposeCaregivers of older persons with eye disease, namely age-related macular degeneration (AMD), have been reported to have a higher than expected distress. Very few studies have explored caregiver perceptions as to what is important when providing care. The aim of this study was to explore the perceptions of caregivers of persons with neovascular AMD in relation to the most important aspects of caring, as described in extended answers to self-administered survey questions.MethodsA cross-sectional, self-administered survey of 643 caregivers of people with neovascular AMD, comprising 27 closed-response questions and 2 open ended questions. The latter were analysed as part of this study utilising and 'inductive' Grounded Theory approach.ResultsSix-hundred and forty-three caregiver responses to 2 open ended questions were analysed using an inductive approach and sorted into thematic networks. Three discrete categories arose: The Impact of Caring; Injections and Information and Activities of Daily Living.ConclusionsMost caregivers were family caregivers and were found to be compassionate and self-sacrificing. They accepted additional responsibility whilst providing an encouraging environment for their care recipient. As a result, they experience distress and consider their own needs as secondary. Very few seek or receive respite and this added burden can have a negative impact upon the relationship between caregiver and care recipient. PMID:26611848

  20. Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration.

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    Jeffrey A Canter

    Full Text Available The objective of this study was to determine if MTND2*LHON4917G (4917G, a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD. A preliminary study of 393 individuals (293 cases and 100 controls ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11. Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study, we were able to match 560 (280 cases and 280 unaffected on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20-3.91, p = 0.01. In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.

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

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    John Paul SanGiovanni

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

  2. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration.

    Science.gov (United States)

    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 (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. PMID:27241461

  3. Management of neovascular Age-related macular degeneration: A review on landmark randomized controlled trials

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    Aniruddha Agarwal

    2016-01-01

    Full Text Available 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.

  4. Association between Blood Lead Levels and Age-Related Macular Degeneration.

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    Ho Sik Hwang

    Full Text Available To investigate the association between blood lead levels and prevalence of age-related macular degeneration (AMD.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.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.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.

  5. Quantification of visual field loss in age-related macular degeneration.

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    Jennifer H Acton

    Full Text Available BACKGROUND: An evaluation of standard automated perimetry (SAP and short wavelength automated perimetry (SWAP for the central 10-2 visual field test procedure in patients with age-related macular degeneration (AMD is presented in order to determine methods of quantifying the central sensitivity loss in patients at various stages of AMD. METHODS: 10-2 SAP and SWAP Humphrey visual fields and stereoscopic fundus photographs were collected in 27 eyes of 27 patients with AMD and 22 eyes of 22 normal subjects. RESULTS: Mean Deviation and Pattern Standard Deviation (PSD varied significantly with stage of disease in SAP (both p<0.001 and SWAP (both p<0.001, but post hoc analysis revealed overlap of functional values among stages. In SWAP, indices of focal loss were more sensitive to detecting differences in AMD from normal. SWAP defects were greater in depth and area than those in SAP. Central sensitivity (within 1° changed by -3.9 and -4.9 dB per stage in SAP and SWAP, respectively. Based on defect maps, an AMD Severity Index was derived. CONCLUSIONS: Global indices of focal loss were more sensitive to detecting early stage AMD from normal. The SWAP sensitivity decline with advancing stage of AMD was greater than in SAP. A new AMD Severity Index quantifies visual field defects on a continuous scale. Although not all patients are suitable for SWAP examinations, it is of value as a tool in research studies of visual loss in AMD.

  6. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization ≤1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

  7. Retinal Image Classification for the Screening of Age-Related Macular Degeneration

    Science.gov (United States)

    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).

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

    Science.gov (United States)

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

    2015-03-01

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

  9. Adaptive optics-assisted optical coherence tomography for imaging of patients with age related macular degeneration

    Science.gov (United States)

    Sudo, Kenta; Cense, Barry

    2013-03-01

    We developed an optical coherence tomography (OCT) prototype with a sample arm that uses a 3.4 mm beam, which is considerably larger than the 1.2 to 1.5 mm beam that is used in commercialized OCT systems. The system is equipped with adaptive optics (AO), and to distinguish it from traditional AO-OCT systems with a larger 6 mm beam we have coined this concept AO-assisted OCT. Compared to commercialized OCT systems, the 3.4 mm aperture combined with AO improves light collection efficiency and imaging lateral resolution. In this paper, the performance of the AOa-OCT system was compared to a standard OCT system and demonstrated for imaging of age-related macular degeneration (AMD). Measurements were performed on the retinas of three human volunteers with healthy eyes and on one eye of a patient diagnosed with AMD. The AO-assisted OCT system imaged retinal structures of healthy human eyes and a patient eye affected by AMD with higher lateral resolution and a 9° by 9° field of view. This combination of a large isoplanatic patch and high lateral resolution can be expected to fill a gap between standard OCT with a 1.2 mm beam and conventional AO-OCT with a 6 mm beam and a 1.5° by 1.5° isoplanatic patch.

  10. Automatic multiresolution age-related macular degeneration detection from fundus images

    Science.gov (United States)

    Garnier, Mickaël.; Hurtut, Thomas; Ben Tahar, Houssem; Cheriet, Farida

    2014-03-01

    Age-related Macular Degeneration (AMD) is a leading cause of legal blindness. As the disease progress, visual loss occurs rapidly, therefore early diagnosis is required for timely treatment. Automatic, fast and robust screening of this widespread disease should allow an early detection. Most of the automatic diagnosis methods in the literature are based on a complex segmentation of the drusen, targeting a specific symptom of the disease. In this paper, we present a preliminary study for AMD detection from color fundus photographs using a multiresolution texture analysis. We analyze the texture at several scales by using a wavelet decomposition in order to identify all the relevant texture patterns. Textural information is captured using both the sign and magnitude components of the completed model of Local Binary Patterns. An image is finally described with the textural pattern distributions of the wavelet coefficient images obtained at each level of decomposition. We use a Linear Discriminant Analysis for feature dimension reduction, to avoid the curse of dimensionality problem, and image classification. Experiments were conducted on a dataset containing 45 images (23 healthy and 22 diseased) of variable quality and captured by different cameras. Our method achieved a recognition rate of 93:3%, with a specificity of 95:5% and a sensitivity of 91:3%. This approach shows promising results at low costs that in agreement with medical experts as well as robustness to both image quality and fundus camera model.

  11. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration

    Science.gov (United States)

    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

  12. Longterm effects of radiation treatment for age-related macular degeneration

    International Nuclear Information System (INIS)

    We reviewed the longterm effect of radiation on age-related macular degeneration in 30 eyes. All the patients were aged 60 years or over. As the criteria for entering the study, all eyes had to show tendency for exacerbation during the past 6 months and the presence of choroidal neovascularization had to be verified by fluorescein angiography. One group of 15 eyes received a total of 10 Gy divided in 5 fractions. The other group of 15 eyes received a total of 20 Gy divided in 10 fractions. Another group of untreated 16 eyes with similar lesions were restrospectively assessed. The irradiated eyes showed beneficial tendencies as compared with the untreated. Final visual acuity of 20/200 was attained in 20% of eyes receiving 10 Gy, 53% of eyes receiving 20 Gy and in no eye which did not receive radiation. The difference was significant (p<0.01). When deterioration of visual acuity is defined as twice of the visual angle, stability or improvement in visual acuity was attained in 47% of eyes treated by 20 Gy and in 13% of untreated eyes. The difference was significant (p<0.01). (author)

  13. Radiation therapy for small choroidal neovascularization in age-related macular degeneration

    International Nuclear Information System (INIS)

    Radiation therapy for age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization smaller than or equal to 1 disc area was evaluated. Fourteen eyes received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten eyes in a control group were followed for an average of 16 months without any treatment. At a 12-month follow-up examination, funduscopic and angiographic findings had improved in 7 eyes (50%), were unchanged in 1 eye (7%) and, had deteriorated in 6 eyes (43%) among the treated patients. The same findings had improved in 1 eye (10%), were unchanged in 2 eyes (20%), and had deteriorated in 7 eyes (70%) among the control patients. There was a statistically significant difference by Mann-Whitney U test between the two groups. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%) among the treated patients. Among the control patients visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference between the two groups was not statistically significant. Of the 7 cases whose fundus had improved by 12 months, 4 cases maintained a favorable status through the following 2 years. Radiation therapy had an inhibitory effect on small choroidal neovascularization when viewed by funduscopy and angiography, but, the efficacy for visual prognosis was not always identified. (author)

  14. Critical Appraisal of Clinical Practice Guidelines for Age-Related Macular Degeneration

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    Annie M. Wu

    2015-01-01

    Full Text Available Purpose. To evaluate the methodological quality of age-related macular degeneration (AMD clinical practice guidelines (CPGs. Methods. AMD CPGs published by the American Academy of Ophthalmology (AAO and Royal College of Ophthalmologists (RCO were appraised by independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE II instrument, which comprises six domains (Scope and Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, and Editorial Independence, and an Overall Assessment score summarizing methodological quality across all domains. Results. Average domain scores ranged from 35% to 83% for the AAO CPG and from 17% to 83% for the RCO CPG. Intraclass correlation coefficients for the reliability of mean scores for the AAO and RCO CPGs were 0.74 and 0.88, respectively. The strongest domains were Scope and Purpose and Clarity of Presentation. The weakest were Stakeholder Involvement (AAO and Editorial Independence (RCO. Conclusions. Future AMD CPGs can be improved by involving all relevant stakeholders in guideline development, ensuring transparency of guideline development and review methodology, improving guideline applicability with respect to economic considerations, and addressing potential conflict of interests within the development group.

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

    Science.gov (United States)

    Chen, Jing; Gupta, Ankur S.; Smith, Lois E. H.

    2015-01-01

    We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD) to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1)-based signaling pathway that converges on DNA-binding transcription complexes through a 3'-5'-cyclic adenosine monophosphate-calcineurin (cAMP-CN)-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs) existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P ≤ 9.48 x 10-5), DCC (Deleted in Colorectal Cancer)—the gene encoding a primary NTN1 receptor (rs8097127, P ≤ 3.03 x 10-5), and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038), supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD. PMID:25950802

  16. Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

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    Kai Fang

    2013-01-01

    Full Text Available Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD. Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB. Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9% gaining ≥15 letters. Change in median CRT was −81.5 μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P=0.028, P<0.001, P=0.02, and P=0.039, resp.. Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P=0.028, and P=0.021, resp.. Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591.

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

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    Akshay Anand

    2013-01-01

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

  18. Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

    Science.gov (United States)

    Örnek, Nurgül; Örnek, Kemal; Aydin, Süleyman; Yilmaz, Musa; Ölmez, Yaşar

    2016-01-01

    AIM To investigate the serum levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and adropin in age-related macular degeneration (AMD) patients. METHODS Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group. Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups. RESULTS AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness (P =0.01, 0.047, 0.025 and AMD patients compared to controls (26.48±6.44 vs 30.42±7.92 ng/mL, PAMD patients (6.17±3.19 vs 5.79±2.71 ng/mL, P=0.4). Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness (r=-0.226, P=0.025) and a significant positive correlation with subfoveal choroidal thickness (r=0.2, P=0.048). CONCLUSION The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD. PMID:27162728

  19. Bevacizumab for neovascular age-related macular degeneration in Chinese patients in a clinical setting

    Science.gov (United States)

    Ng, Danny Siu-Chun; Kwok, Alvin Kwan-Ho; Tong, Justin Man-Kit; Chan, Clement Wai-Nang; Li, Walton Wai-Tat

    2016-01-01

    AIM To determine the outcome of non-investigational treatment with intravitreal bevacizumab (IVB) in neovascular age-related macular degeneration (AMD) patients. METHODS Retrospective chart review of 81 eyes with neovascular AMD followed-up for at least 12mo and received 3-monthly loading IVB injections. Re-treat was based upon the individual clinician's judgment. Best-corrected visual acuity (BCVA) and optical coherence tomography measurements of central foveal thickness outcomes were evaluated at 12, 24mo. RESULTS Eighty-one eyes (of 75 patients) completed 12mo of follow-up and 44 eyes (of 41 patients) completed 24mo of follow-up. The mean baseline logMAR BCVA significantly improved from 0.94±0.69 to 0.85±0.68 at 12mo (PAMD patients. Poor baseline visual acuity and prior PDT treatment may also improve vision after IVB. The safety and durability of effect was maintained at 24mo. PMID:27158614

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Recent developments in the management of dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Buschini E

    2015-04-01

    Full Text Available Elisa Buschini, Antonio M Fea, Carlo A Lavia, Marco Nassisi, Giulia Pignata, Marta Zola, Federico M Grignolo Ospedale Oftalmico, Ophthalmic Section, Department of Clinical Pathophysiology, University of Turin, Turin, Italy Abstract: Dry age-related macular degeneration (AMD, also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%, dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6 are under evaluation, but the results are still uncertain. New strategies aim to 1 reduce or block drusen formation, 2 reduce or eliminate inflammation, 3 lower the accumulation of toxic by-products from the visual cycle, 4 reduce or eliminate retinal oxidative stress, 5 improve choroidal perfusion, 6 replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7 develop a target gene therapy. Keywords: dry AMD, geographic atrophy, new AMD therapy

  3. Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Khanani AM

    2015-07-01

    Full Text Available Arshad M Khanani Sierra Eye Associates, Reno, NV, USA Purpose: To evaluate the durability of fixed bimonthly dosing of intravitreal aflibercept for neovascular age-related macular degeneration.Methods: Records of 16 patients were retrospectively reviewed. Patients received three initial 2.0 mg monthly doses of aflibercept then 8-weekly doses according to the product label. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters, central macular thickness, fluid on optical coherence tomography, and pigment epithelial detachment (PED were measured.Results: Prior to starting aflibercept, 13 patients had subretinal fluid (SRF, five had intraretinal fluid (IRF, four had PED, and baseline visual acuity (VA was 62 approximate ETDRS letters. Following the monthly dosing, seven patients had no improvement or decreased VA, ten patients still had SRF/IRF, and PED had worsened in one patient. At Visit 4, an average of 6.8 weeks after Visit 3, VA had decreased in seven patients, SRF/IRF had increased in 12 patients, and PED had returned in all patients who initially responded. Based on the presence of fluid after the initial monthly injections, 12 patients could not be extended to fixed bimonthly dosing.Conclusion: This case series adds to the growing body of evidence on the need for flexible dosing schedules for the personalized treatment of neovascular age-related macular degeneration. Keywords: age-related macular degeneration, AMD, bimonthly, regimen, aflibercept, case studies, retinal fluid

  4. The chronic care for age-related macular degeneration study (CHARMED: Study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Held Ulrike

    2011-10-01

    Full Text Available Abstract Background Neovascular age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. As in other chronic diseases, several effective treatments are available, but in clinical daily practice there is an evidence performance gap. The Chronic Care Model represents an evidence-based framework for the care of chronically ill patients and aims at closing that gap. However, no data are available regarding patients with neovascular age-related macular degeneration. Methods/Design CHARMED is a multicenter randomized controlled trial. The study challenges the hypothesis that the implementation of core elements of the Chronic Care Model (patient empowerment, delivering evidence based information, clinical information system, reminder system with structured follow up and frequent monitoring via a specially trained Chronic Care Coach in Swiss centres for neovascular age-related macular degeneration results in better visual acuity (primary outcome and an increased disease specific quality of life (secondary outcome in patients with neovascular age-related macular degeneration. According to the power calculation, a total sample size of 352 patients is needed (drop out rate of 25%. 14 specialised medical doctors from leading ophtalmologic centres in Switzerland will include 25 patients. In each centre, a Chronic Care Coach will provide disease specific care according to the Chronic Care Model for intervention group. Patients from the control group will be treated as usual. Baseline measurements will be taken in month III - XII, starting in March 2011. Follow-up data will be collected after 6 months and 1 year. Discussion Multiple studies have shown that implementing Chronic Care Model elements improve clinical outcomes as well as process parameters in different chronic diseases as osteoarthritis, depression or e.g. the cardiovascular risk profile of diabetes patients. This

  5. The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration

    OpenAIRE

    Stringham, J.M; Hammond, BR; Nolan, John; Wooten, BR; Mammen, A.; Smollen, W

    2008-01-01

    The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curv...

  6. Intravitreal Aflibercept Outcomes in Patients with Persistent Macular Exudate Previously Treated with Bevacizumab and/or Ranibizumab for Neovascular Age-Related Macular Degeneration

    OpenAIRE

    David R. Griffin; Richmond, Preston P; John C. Olson

    2014-01-01

    Purpose. To assess whether intravitreal aflibercept (2.0 mg) can effectively reduce persistent macular exudate and enhance visual acuity in ranibizumab (0.5 mg) and/or bevacizumab (1.25 mg) treatment resistant patients with neovascular age-related macular degeneration. Methods. This retrospective study included 47 treatment resistant eyes from 47 patients switched to intravitreal aflibercept injections after receiving a minimum of 3 injections with either ranibizumab or bevacizumab. Snellen v...

  7. Foveal-Sparing Scotomas in Advanced Dry Age-Related Macular Degeneration

    Science.gov (United States)

    Sunness, Janet S.; Rubin, Gary S.; Zuckerbrod, Abraham; Applegate, Carol A.

    2008-01-01

    Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to "fit" within the central spared area. (Contains 2 tables…

  8. Early and exudative age-related macular degeneration is associated with increased plasma levels of soluble TNF receptor II

    DEFF Research Database (Denmark)

    Faber, Carsten; Jehs, Tina; Juel, Helene Baek; Singh, Amardeep; Falk, Mads Krüger; Sørensen, Torben Lykke; Nissen, Mogens Holst

    2015-01-01

    PURPOSE: We have recently identified homeostatic alterations in the circulating T cells of patients with age-related macular degeneration (AMD). In cultures of retinal pigment epithelial cells, we have demonstrated that T-cell-derived cytokines induced the upregulation of complement, chemokines and...... other proteins implicated in AMD pathogenesis. The purpose of this study was to test whether increased plasma levels of cytokines were present in patients with AMD. METHODS: We conducted a case-control study. Age-related macular degeneration status was assessed using standardized multimodal imaging...... forms of AMD and 74 controls. Significantly increased levels of sTNFRII were observed in patients with early or exudative AMD (p < 0.01). After adjusting for CFH Y402H genotype, age, sex and smoking history, the level of sTNFRII remained a significant predictor for prevalence of AMD with odds ratios at...

  9. Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Møller, Flemming; Sjølie, Anne Katrin;

    2010-01-01

    previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow-up was......PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26...... performed at 1 week, 6 weeks, 3 months, and 6 months. RESULTS: Mean multifocal electroretinography P1 amplitudes were significantly improved at 1 week in the central zone and after 3 and 6 months, improvement was seen in all 6 concentric rings corresponding to +/-25 degrees of the central visual field. Full...

  10. ALGORITHM OF DIAGNOSTICS AND TREATMENT OF AN AGE-RELATED MACULAR DEGENERATION AT PATIENTS WITH CHRONIC PERIPHERAL UVEITIS

    Directory of Open Access Journals (Sweden)

    Yu. I. Khoroshikh

    2015-12-01

    Full Text Available The results of clinical trial of various approaches in treatment the exudative forms of macular degenerations, including age-related, against chronic slow intensity inflammatory process on the extreme retinal periphery of an eye are described in represented material. There were 91 patients (105 eyes in the research with different types of an exudative macular degeneration. The general criteria of inclusion were: age of 18–80 years old, complaints to discomfort in eyes, a spot before an eye, distortions and decrease in the central sight, ophthalmoscopic symptoms of hypostasis in the central and peripheral areas of a retina. It is analyzed the general criteria of diagnostics and treatment of the disease in the article. Considering defeat of the chorioretinal structures located near the ora serrata at persons of young and advanced age. Practical recommendations to a choice of methods of diagnostics and treatment of various clinical and morphological forms of the disease are made. Screening methods of identification of patients with the peripheral uveitis are offered. The scheme of risk calculation of development the macular pathology at persons with changes on the extreme periphery of a retina, that can be used as a method of prevention of development predictively adverse of “wet" forms of an age-related macular degeneration, by means of timely sparing treatment at patients with chronic inflammatory diseases of eyes is given.

  11. Smoking, Antioxidant Supplementation and Dietary Intakes among Older Adults with Age-Related Macular Degeneration over 10 Years

    OpenAIRE

    Gopinath, Bamini; Flood, Victoria M; Kifley, Annette; Liew, Gerald; Mitchell, Paul

    2015-01-01

    We aimed to compare the micronutrient usage and other lifestyle behaviors over 10 years among those with and without age-related macular degeneration (AMD). 1612 participants aged 49+ years at baseline were re-examined over 10 years, west of Sydney, Australia. AMD was assessed from retinal photographs. Dietary data were collected using a semi-quantitative food frequency questionnaire. Smoking status was self-reported. 56 participants had any AMD at baseline, of these 25% quit smoking at 5 yea...

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

    OpenAIRE

    VAVVAS, DEMETRIOS G.; Daniels, Anthony B.; Kapsala, Zoi G.; Goldfarb, Jeremy W.; Emmanuel Ganotakis; Loewenstein, John I.; Young, Lucy H.; GRAGOUDAS, EVANGELOS S.; Dean Eliott; Kim, Ivana K; Miltiadis K. Tsilimbaris; Joan W. Miller

    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 li...

  13. Verteporfin photodynamic therapy combined with intravitreal ranibizumab in neovascular age-related macular degeneration: 24-month follow-up

    OpenAIRE

    Rosalia Giustolisi; Fernanda Pacella; Olga Mastrangelo; Gabriella Cirigliano; Francesca Arienzo; Simone De Gaetano; Elena Pacella

    2014-01-01

    Purpose: to evaluate the efficacy and safety of combined therapy with Photodynamic Therapy with Verteporfin (PDT-V) and intravitreal ranibizumab same-day compared with monotherapy with ranibizumab (three monthly injections ) for the treatment of the choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). Type of study : open-label, randomized controlled trial (RCT). Materials and Methods: 17 eyes of 17 patients were consecutively enrolled and randomly assigned ...

  14. Refractive Error and Risk of Early or Late Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

    OpenAIRE

    Li, Ying; Wang, Jiwen; Zhong, Xiaojing; Tian, Zhen; Wu, Peipei; Zhao, Wenbo; Jin, Chenjin

    2014-01-01

    Objective To summarize relevant evidence investigating the associations between refractive error and age-related macular degeneration (AMD). Design Systematic review and meta-analysis. Methods We searched Medline, Web of Science, and Cochrane databases as well as the reference lists of retrieved articles to identify studies that met the inclusion criteria. Extracted data were combined using a random-effects meta-analysis. Studies that were pertinent to our topic but did not meet the criteria ...

  15. Age-Related Macular Degeneration Is Associated with Less Physical Activity among US Adults: Cross-Sectional Study

    OpenAIRE

    Loprinzi, Paul D.; Swenor, Bonnielin K.; Ramulu, Pradeep Y.

    2015-01-01

    Background We have a limited understanding of the effects of age-related macular degeneration (AMD) on physical activity (PA), and we have no prevalence estimates of the daily movement patterns among Americans with AMD. Therefore, we examined the association between AMD and PA and provided estimates of the daily movement patterns of Americans with AMD. Methods Data from the 2005-2006 National Health and Nutrition Examination Survey were used, including 1,656 adults (40-85 yrs). Retinal imagin...

  16. Pathway activation profiling reveals new insights into Age-related Macular Degeneration and provides avenues for therapeutic interventions

    OpenAIRE

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

    2014-01-01

    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/choro...

  17. Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy

    OpenAIRE

    Ke Liu; Lai, Timothy Y. Y.; Li Ma; Lai, Frank H. P.; Young, Alvin L.; Marten E. Brelen; Tam, Pancy O.S.; Chi Pui Pang; Li Jia Chen

    2015-01-01

    Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene with neovascular AMD and PCV. Two haplotype-tagging SNPs, rs1005510 and rs11603020, of SERPING1 were genotyped in 708 unrelated Chinese individuals: 200 neovascular AMD, 233 P...

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

    OpenAIRE

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

    2015-01-01

    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 photog...

  19. Mitochondrial Haplogroups and Control Region Polymorphisms in Age-Related Macular Degeneration: A Case-Control Study

    OpenAIRE

    Mueller, Edith E.; Schaier, Elena; Brunner, Susanne M.; Eder, Waltraud; Mayr, Johannes A.; Egger, Stefan F.; Nischler, Christian; Oberkofler, Hannes; Reitsamer, Herbert A.; Patsch, Wolfgang; Sperl, Wolfgang; Kofler, Barbara

    2012-01-01

    Background Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA) are postulated to be s...

  20. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

    OpenAIRE

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, popula...

  1. Modelling Cost Effectiveness in Neovascular Age-Related Macular Degeneration: The Impact of Using Contrast Sensitivity vs. Visual Acuity.

    OpenAIRE

    Butt, T.; Patel, P. J.; Tufail, A; Rubin, G. S.

    2014-01-01

    Background The cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avasti...

  2. Bevacizumab versus Ranibizumab on As-Needed Treatment Regimen for Neovascular Age-Related Macular Degeneration in Turkish Patients

    OpenAIRE

    Abdullah Ozkaya; Zeynep Alkin; Yalcin Karakucuk; Dilek Yasa; Ahmet Taylan Yazici; Ahmet Demirok

    2013-01-01

    Purpose. To compare the efficacy of intravitreal bevacizumab versus ranibizumab in the treatment of neovascular age-related macular degeneration (nAMD). Methods. Retrospective, comparative study. The newly diagnosed nAMD patients who were treated with intravitreal bevacizumab or ranibizumab on an as-needed treatment regimen were included in the study. Main outcome measures were the change in best corrected visual acuity (BCVA), and central retinal thickness (CRT). Secondary outcome measures w...

  3. Bevacizumab and ranibizumab for neovascular age-related macular degeneration: an updated meta-analysis of randomised clinical trials

    OpenAIRE

    Kodjikian, Laurent; Decullier, Evelyne; Souied, Eric H; Girmens, Jean-François; Durand, Emilie E.; Chapuis, François R.; Huot, Laure

    2014-01-01

    Purpose Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year. Methods A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trial...

  4. Intravitreal Expansile Gas and Bevacizumab Injection for Submacular Hemorrhage Due to Neovascular Age-related Macular Degeneration

    OpenAIRE

    Ramin Nourinia; Mohammad Bonyadi; Hamid Ahmadieh

    2010-01-01

    Purpose: To evaluate the results of intravitreal expansile gas injection, with or without recombinant tissue plasminogen activator (rtPA), followed by intravitreal bevacizumab injection for treatment of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD). Methods: In this interventional case series, 5 eyes of 5 patients with SMH secondary to choroidal neovascularization (CNV) due to neovascular AMD were treated with 0.3 cc intravitreal SF6 (and 50 μ...

  5. M-charts as a tool for quantifying metamorphopsia in age-related macular degeneration treated with the bevacizumab injections

    OpenAIRE

    Nowomiejska, Katarzyna; Oleszczuk, Agnieszka; Brzozowska, Agnieszka; Grzybowski, Andrzej; Ksiazek, Katarzyna; Maciejewski, Ryszard; Ksiazek, Piotr; Jünemann, Anselm; Rejdak, Robert

    2013-01-01

    Background This article is aimed to assess quantitatively metamorphopsia using M-charts in patients suffering from wet age-related macular degeneration (AMD) treated with the intravitreal bevacizumab injections and to compare the results with traditional Amsler grid and ocular coherence tomography (OCT). Methods Thirty-six patients diagnosed with wet AMD were examined one day before and one month after the intraocular injection of bevacizumab. Horizontal and vertical metamorphopsia scores usi...

  6. The chronic care for age-related macular degeneration study (CHARMED): Study protocol for a randomized controlled trial

    OpenAIRE

    Held Ulrike; Wang Mathyas; Woitzek Katja; Frei Anja; Rosemann Thomas

    2011-01-01

    Abstract Background Neovascular age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. As in other chronic diseases, several effective treatments are available, but in clinical daily practice there is an evidence performance gap. The Chronic Care Model represents an evidence-based framework for the care of chronically ill patients and aims at closing that gap. However, no data are available regarding patients ...

  7. Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

    OpenAIRE

    McKay, Gareth J; Patterson, Chris C; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R; Ho, Lintje; de Jong, Paulus T V M; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis

    2011-01-01

    Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplo...

  8. Age-related macular degeneration: clinical findings, histopathology and imaging techniques.

    Science.gov (United States)

    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. PMID:24732758

  9. Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Janusz Blasiak

    2013-01-01

    Full Text Available Aging and oxidative stress seem to be the most important factors in the pathogenesis of age-related macular degeneration (AMD, a condition affecting many elderly people in the developed world. However, aging is associated with the accumulation of oxidative damage in many biomolecules, including DNA. Furthermore, mitochondria may be especially important in this process because the reactive oxygen species produced in their electron transport chain can damage cellular components. Therefore, the cellular response to DNA damage, expressed mainly through DNA repair, may play an important role in AMD etiology. In several studies the increase in mitochondrial DNA (mtDNA damage and mutations, and the decrease in the efficacy of DNA repair have been correlated with the occurrence and the stage of AMD. It has also been shown that mitochondrial DNA accumulates more DNA lesions than nuclear DNA in AMD. However, the DNA damage response in mitochondria is executed by nucleus-encoded proteins, and thus mutagenesis in nuclear DNA (nDNA may affect the ability to respond to mutagenesis in its mitochondrial counterpart. We reported that lymphocytes from AMD patients displayed a higher amount of total endogenous basal and oxidative DNA damage, exhibited a higher sensitivity to hydrogen peroxide and UV radiation, and repaired the lesions induced by these factors less effectively than did cells from control individuals. We postulate that poor efficacy of DNA repair (i.e., is impaired above average for a particular age when combined with the enhanced sensitivity of retinal pigment epithelium cells to environmental stress factors, contributes to the pathogenesis of AMD. Collectively, these data suggest that the cellular response to both mitochondrial and nuclear DNA damage may play an important role in AMD pathogenesis.

  10. Complement factor H gene polymorphisms and Chlamydia pneumoniae infection in age-related macular degeneration

    Science.gov (United States)

    Haas, P; Steindl, K; Schmid-Kubista, KE; Aggermann, T; Krugluger, W; Hageman, GS; Binder, S

    2014-01-01

    Purpose To investigate the association of the complement factor H gene (CFH) Y402H polymorphism and age-related macular degeneration (AMD) in the Austrian population (Caucasoid descent), and to determine whether there is an association between exposure to Chlamydia pneumoniae—responsible for up to 20% of community-acquired pneumoniae—and the AMD-associated CFH risk polymorphism. Methods Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 75 unrelated AMD patients and compared with 75 healthy, age-matched control subjects. C. pneumoniae serum IgG was tested by ELISA (R&D) in both groups. The association between the CFH Y402H genetic polymorphism and the disease was examined by χ2-test and logistic regression. Results CFH Y402H genotype frequencies differed significantly between AMD patients and healthy controls (1277 TT, 22.7%; 1277 TC, 53.3%; and 1277 CC, 22.7% in the AMD group; 1277 TT, 48.0%; 1277 TC, 38.7%; and 1277 CC, 13.3% in the control group) showing a P-value <0.005 (OR:2.920/3.811). No association was found between a positive C. pneumoniae titre and AMD (P = 0.192), nor was any association found between C. pneumoniae and the CFH Y402H polymorphism. Conclusions Our data confirm that the CFH Y402H polymorphism is a risk factor for AMD in the Austrian population with a higher frequency of the Y402 polymorphism in AMD patients. No association between preceding C. pneumoniae infection and diagnosed AMD was found. PMID:19169230

  11. Current and emerging therapies for the treatment of age-related macular degeneration.

    Science.gov (United States)

    Emerson, M Vaughn; Lauer, Andreas K

    2008-06-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV) due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF) therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA) to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary neurotrophic factor is currently being studied for the inhibition of progression of geographic atrophy. Combination therapy has been

  12. A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration.

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    Kee Dong Yoon

    Full Text Available Aging of retinal pigment epithelial (RPE cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD. Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC with electrospray ionization mass spectrometry (ESI-MS we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO and methylglyoxal (MG, that are known to modify proteins by advanced glycation endproduct (AGE formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye.

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

    Directory of Open Access Journals (Sweden)

    Evans Christopher

    2010-12-01

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

  14. High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration

    Science.gov (United States)

    Pertl, Laura; Kern, Sabine; Weger, Martin; Hausberger, Silke; Trieb, Markus; Gasser-Steiner, Vanessa; Haas, Anton; Scharnagl, Hubert; Heinemann, Akos; Marsche, Gunther

    2016-01-01

    Purpose High-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients. Methods Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants. Results In our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (pAMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, pAMD subjects (MD -24.1, pAMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis. PMID:27171197

  15. Serum antioxidants and age-related macular degeneration among older Japanese.

    Science.gov (United States)

    Michikawa, Takehiro; Ishida, Susumu; Nishiwaki, Yuji; Kikuchi, Yuriko; Tsuboi, Tazuru; Hosoda, Kanae; Ishigami, Ai; Iwasawa, Satoko; Nakano, Makiko; Takebayashi, Toru

    2009-01-01

    From the perspective of human nutrition, the prevention of age-related macular degeneration (AMD) through diet control is feasible and desirable. We investigated the relationship between serum antioxidants and AMD in the community-dwelling older Japanese eating a typical Japanese diet. In this study, 722 subjects aged 65 years or older (297 males and 425 females) who had gradable fundus photographs were included. The subjects were divided into three groups of early or late AMD or non-maculopathy. Serum antioxidants (alpha-, gamma-tocopherols, retinol, beta-cryptoxanthin, alpha-, beta-carotenes, lycopene, and lutein and zeaxanthin) were measured with high-performance liquid chromatography. To clarify the combined effect as the group of the antioxidants, we defined the carotene family (alpha-, beta-carotenes and lycopene) and carotenoid family (beta-cryptoxanthin, alpha-, beta-carotenes, lycopene, lutein and zeaxanthin). Tertiles of each serum antioxidant were obtained and the prevalence of early or late AMD was compared with univariate or multivariate analysis. The overall prevalence of early AMD was 4.4% (95% confidence interval: 3.1-6.2) and late AMD was 1.1% (0.5-2.2). Only alpha-tocopherol and beta-cryptoxanthin were related to late AMD as single antioxidants. On the other hand, the carotene and carotenoid families as a combination of antioxidants were protectively associated with late AMD. No relationship was found between serum antioxidants and early AMD. Our findings support the hypothesis that a combination of serum antioxidants obtained from the traditional Japanese diet is protective for late AMD, but not for early AMD. PMID:19329388

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

    Science.gov (United States)

    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. PMID:22192508

  17. Stereotactic targeting and dose verification for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Gertner, Michael; Chell, Erik; Pan, Kuang-Hung; Hansen, Steve; Kaiser, Peter K.; Moshfeghi, Darius M. [Oraya Therapeutics, Inc., Newark, California 94560 (United States); Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44915 (United States); Department of Ophthalmology, Stanford University, Stanford, California 94305 (United States)

    2010-02-15

    Purpose: Validation of the targeting and dose delivery of the IRay low voltage age-related macular degeneration treatment system. Methods: Ten human cadaver eyes were obtained for this study and mounted in the IRay system. Using gel and vacuum, an I-Guide immobilization device was coupled to the eyes and radiochromic film was affixed to the posterior aspect of the globes. Three narrow x-ray beams were delivered through the pars plana to overlap on the predicted nominal fovea. A needle was placed through the center of the film's beam spot and into the eye to register the film and the inner retina. The process was performed three times for each of the ten eyes (30 simulated treatments; 90 individual beams). The globes were dissected to assess the targeting accuracy by measuring the distances from the needles to the fovea. The dose to the fovea was calculated from the radiochromic film. Results: X-ray targeting on the retina averaged 0.6{+-}0.4 mm from the fovea. Repeated treatments on the same eye showed a reproducibility of 0.4{+-}0.4 mm. The optic nerve was safely avoided, with the 90% isodose edge of the beam spot between 0.4 and 2.6 mm from the edge of the optic disk. Measured dose matched that prescribed. Conclusions: This study provides confidence that the IRay, with an average accuracy of 0.6 mm and a precision of 0.4 mm, can reliably treat most AMD lesions centered on the fovea. With the exception of motion, all sources of error are included.

  18. Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

    Science.gov (United States)

    Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

    2012-10-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

  19. Long-term results after external radiotherapy in age-related macular degeneration. A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Prettenhofer, U.; Mayer, R.; Stranzl, H.; Oechs, A.; Hackl, A. [Dept. of Radiotherapy, Univ. Medical School, Graz (Austria); Haas, A. [Dept. of Opthalmology, Univ. Medical School, Graz (Austria)

    2004-02-01

    Purpose: to prospectively evaluate the short- and long-term efficacy of external radiotherapy (RT) in patients with age-related macular degeneration (AMD) by comparing two different dose schedules. Patients and methods: in this prospective, nonrandomized, comparative study including 80 patients, the efficacy of external RT with a total dose of 14.4 Gy (group A, n = 40) and 25.2 Gy (group B, n = 40) was compared. Patients of group a were irradiated between September 1995 and July 1996, patients of group b between August 1996 and November 1997. 67 patients presented with occult choroidal neovascularization (CNV), 13 with classic subfoveal lesions. Complete ophthalmologic investigation was performed before RT, at intervals of 3 months during the 1st year after RT, and of 6 months thereafter. Results: 12 months after RT, vision deteriorated in 85% (14.4 Gy) and 65% (25.2 Gy) of patients. Central visual field decreased with both dose schedules. There was no morphological benefit in neovascular changes. After 48 months, complete follow-up was possible in 46 patients who showed a significant loss of vision similar to the natural course of AMD. Conclusion: external RT of AMD with 14.4 Gy as well as with the escalated dose of 25.2 Gy showed a poor beneficial outcome after 6 and 12 months, respectively. After a follow-up of 4 years, visual outcome in irradiated patients was similar to the natural course of the disease. A conspicuous efficacy of RT in prevention of blindness could not be demonstrated. (orig.)

  20. Stereotactic targeting and dose verification for age-related macular degeneration

    International Nuclear Information System (INIS)

    Purpose: Validation of the targeting and dose delivery of the IRay low voltage age-related macular degeneration treatment system. Methods: Ten human cadaver eyes were obtained for this study and mounted in the IRay system. Using gel and vacuum, an I-Guide immobilization device was coupled to the eyes and radiochromic film was affixed to the posterior aspect of the globes. Three narrow x-ray beams were delivered through the pars plana to overlap on the predicted nominal fovea. A needle was placed through the center of the film's beam spot and into the eye to register the film and the inner retina. The process was performed three times for each of the ten eyes (30 simulated treatments; 90 individual beams). The globes were dissected to assess the targeting accuracy by measuring the distances from the needles to the fovea. The dose to the fovea was calculated from the radiochromic film. Results: X-ray targeting on the retina averaged 0.6±0.4 mm from the fovea. Repeated treatments on the same eye showed a reproducibility of 0.4±0.4 mm. The optic nerve was safely avoided, with the 90% isodose edge of the beam spot between 0.4 and 2.6 mm from the edge of the optic disk. Measured dose matched that prescribed. Conclusions: This study provides confidence that the IRay, with an average accuracy of 0.6 mm and a precision of 0.4 mm, can reliably treat most AMD lesions centered on the fovea. With the exception of motion, all sources of error are included.

  1. Long-term results after external radiotherapy in age-related macular degeneration. A prospective study

    International Nuclear Information System (INIS)

    Purpose: to prospectively evaluate the short- and long-term efficacy of external radiotherapy (RT) in patients with age-related macular degeneration (AMD) by comparing two different dose schedules. Patients and methods: in this prospective, nonrandomized, comparative study including 80 patients, the efficacy of external RT with a total dose of 14.4 Gy (group A, n = 40) and 25.2 Gy (group B, n = 40) was compared. Patients of group a were irradiated between September 1995 and July 1996, patients of group b between August 1996 and November 1997. 67 patients presented with occult choroidal neovascularization (CNV), 13 with classic subfoveal lesions. Complete ophthalmologic investigation was performed before RT, at intervals of 3 months during the 1st year after RT, and of 6 months thereafter. Results: 12 months after RT, vision deteriorated in 85% (14.4 Gy) and 65% (25.2 Gy) of patients. Central visual field decreased with both dose schedules. There was no morphological benefit in neovascular changes. After 48 months, complete follow-up was possible in 46 patients who showed a significant loss of vision similar to the natural course of AMD. Conclusion: external RT of AMD with 14.4 Gy as well as with the escalated dose of 25.2 Gy showed a poor beneficial outcome after 6 and 12 months, respectively. After a follow-up of 4 years, visual outcome in irradiated patients was similar to the natural course of the disease. A conspicuous efficacy of RT in prevention of blindness could not be demonstrated. (orig.)

  2. Radiotherapy for age-related macular degeneration: preliminary results of a potentially new treatment

    International Nuclear Information System (INIS)

    Purpose: Neovascular macular degeneration is the leading cause of severe blindness in North America today. Limited treatments are available for this disease process. A Phase I/II study was performed to determine the toxicity and efficacy of external beam radiotherapy in patients with age-related subfoveal neovascularization. Methods and Materials: Between March 1994 and June 1995, 52 patients with a mean age of 80 (60-92) were enrolled. These patients were either not eligible or were poor candidates for laser photocoagulation, primarily because of the subfoveal location of the neovascularization. Initial visual acuities ranged from 20 out of 32 to finger counting at 3 feet. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Patients were treated with a single lateral 4- or 6-MV photon beam, to a dose of 14-15 Gy in eight fractions over 10 days. The field size averaged 5 x 3 cm. Results: No significant acute morbidity was noted. All patients underwent ophthalmic examinations and repeat angiography at 1 and 3 months posttreatment and then at 3-month intervals. With a mean follow-up of 7 months (3-18 months), 41 patients (79%) are within two lines of their pretreatment visual acuity. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 34 patients (65%). New neovascular membranes have been noted in five patients. Conclusions: It appears that radiotherapy can affect active subretinal neovascularization, but it is unlikely to prevent new neovascular events produced by this chronic disease. Further investigation is warranted

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

    International Nuclear Information System (INIS)

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

  4. Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

    International Nuclear Information System (INIS)

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30–3.26 for the investigated concentration range of 1–7 mg g−1, respectively. In comparison, for the same concentration range, nDEF values of 1.32–3.40, 1.31–3.33, 1.29–3.19, 1.28–3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD. (paper)

  5. Whole Exome Sequencing in Patients with the Cuticular Drusen Subtype of Age-Related Macular Degeneration

    Science.gov (United States)

    Duvvari, Maheswara R.; van de Ven, Johannes P. H.; Geerlings, Maartje J.; Saksens, Nicole T. M.; Bakker, Bjorn; Henkes, Arjen; Neveling, Kornelia; del Rosario, Marisol; Westra, Dineke; van den Heuvel, Lambertus P. W. J.; Schick, Tina; Fauser, Sascha; Boon, Camiel J. F.; Hoyng, Carel B.; de Jong, Eiko K.; den Hollander, Anneke I.

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people worldwide. Cuticular drusen (CD) is a clinical subtype of AMD, which typically displays an earlier age at onset, and has a strong genetic component. Genetic studies support a role for rare sequence variants in CD susceptibility, and rare sequence variants in the CFH gene have been identified in 8.8% of CD cases. To further explore the role of rare variants in CD, we performed whole exome sequencing (WES) in 14 affected members of six families and 12 sporadic cases with CD. We detected rare sequence variants in CFH and FBLN5, which previously were shown to harbor rare variants in patients with CD. In addition, we detected heterozygous rare sequence variants in several genes encoding components of the extracellular matrix (ECM), including FBLN1, FBLN3/EFEMP1, FBLN5, FBLN6/HMCN1, FBN2, and COL15A1. Two rare pathogenic variants were identified in the COL15A1 gene: one in a sporadic case and another was found to segregate in a family with six affected individuals with CD. In addition, two rare pathogenic variants were identified in the FGL1 gene in three unrelated CD cases. These findings suggest that alterations in the ECM and in the coagulation pathway may play a role in the pathogenesis of CD. The identified candidate genes require further analyses in larger cohorts to confirm their role in the CD subtype of AMD. No evidence was found of rare sequence variants in a single gene that segregate with CD in the six families, suggesting that the disease is genetically heterogeneous. PMID:27007659

  6. Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study.

    Directory of Open Access Journals (Sweden)

    Audrey Cougnard-Grégoire

    Full Text Available 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 elderly patients with high HDL

  7. Cost-Utility Analyses of Cataract Surgery in Advanced Age-Related Macular Degeneration

    Science.gov (United States)

    Ma, Yingyan; Huang, Jiannan; Zhu, Bijun; Sun, Qian; Miao, Yuyu; Zou, Haidong

    2016-01-01

    ABSTRACT Purpose To explore the cost-utility of cataract surgery in patients with advanced age-related macular degeneration (AMD). Methods Patients who were diagnosed as having and treated for age-related cataract and with a history of advanced AMD at the Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, were included in the study. All of the participants underwent successful phacoemulsification with foldable posterior chamber intraocular lens implantation under retrobulbar anesthesia. Best-corrected visual acuity (BCVA) and utility value elicited by time trade-off method from patients at 3-month postoperative time were compared with those before surgery. Quality-adjusted life years (QALYs) gained in a lifetime were calculated at a 3% annual discounted rate. Costs per QALY gained were calculated using the bootstrap method, and probabilities of being cost-effective were presented using a cost-effectiveness acceptability curve. Sensitivity analyses were performed to test the robustness of the results. Results Mean logarithm of the minimum angle of resolution BCVA in the operated eye increased from 1.37 ± 0.5 (Snellen, 20/469) to 0.98 ± 0.25 (Snellen, 20/191) (p < 0.001); BCVA in the weighted average from both eyes (=75% better eye + 25% worse eye) was changed from 1.13 ± 0.22 (Snellen, 20/270) to 0.96 ± 0.17 (Snellen, 20/182) (p < 0.001). Utility values from both patients and doctors increased significantly after surgery (p < 0.001 and p = 0.007). Patients gained 1.17 QALYs by cataract surgery in their lifetime. The cost per QALY was 8835 Chinese yuan (CNY) (1400 U.S. dollars [USD]). It is cost-effective at the threshold of 115,062 CNY (18,235 USD) per QALY in China recommended by the World Health Organization. The cost per QALY varied from 7045 CNY (1116 USD) to 94,178 CNY (14,925 USD) in sensitivity analyses. Conclusions Visual acuity and quality of life assessed by utility value improved significantly after surgery

  8. A circulating microrna profile is associated with late-stage neovascular age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV AMD (hsa-mir-301-3p, pcorrected = 5.6*10-5, hsa-mir-361-5p, pcorrected = 8.0*10-4 and hsa-mir-424-5p, pcorrected = 9.6*10-3. A combined profile of the three miRNAs revealed an area under the curve (AUC value of 0.727 and was highly associated with NV AMD (p = 1.2*10-8. To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (pcorrected<0.005. Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGFβ, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay.

  9. Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina

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    Singh Brij B

    2011-08-01

    Full Text Available Abstract Background Alzheimer's disease (AD and age-related macular degeneration (AMD share several pathological hallmarks including β-amyloid (Aβ accumulation, oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely multi-factorial with several factors such as diet, environment, and genetic susceptibility participating in the pathogenesis of these diseases. Epidemiological studies correlated high plasma cholesterol levels with high incidence of AD, and feeding rabbits with a diet rich in cholesterol has been shown to induce AD-like pathology in rabbit brain. High intake of cholesterol and saturated fat were also long been suspected to increase the risk for AMD. However, the extent to which cholesterol-enriched diet may also cause AMD-like features in rabbit retinas is not well known. Methods Male New Zealand white rabbits were fed normal chow or a 2% cholesterol-enriched diet for 12 weeks. At necropsy, animals were perfused with Dulbecco's phosphate-buffered saline and the eyes were promptly removed. One eye of each animal was used for immunohistochemistry and retina dissected from the other eye was used for Western blot, ELISA assays, spectrophotometry and mass spectrometry analyses. Results Increased levels of Aβ, decreased levels of the anti-apoptotic protein Bcl-2, increased levels of the pro-apoptotic Bax and gadd153 proteins, emergence of TUNEL-positive cells, and increased generation of reactive oxygen species were found in retinas from cholesterol-fed compared to normal chow-fed rabbits. Additionally, astrogliosis, drusen-like debris and cholesterol accumulations in retinas from cholesterol-fed rabbits were observed. As several lines of evidence suggest that oxidized cholesterol metabolites (oxysterols may be the link by which cholesterol contributes to the pathogenesis of AMD, we determined levels of oxysterols and found a dramatic increase in levels of oxysterols in retinas from cholesterol-fed rabbits

  10. Age-related macular degeneration is associated with increased proportion of CD56(+) T cells in peripheral blood

    DEFF Research Database (Denmark)

    Faber, Carsten; Singh, Amardeep; Krüger Falk, Mads; Juel, Helene Bæk; Sørensen, Torben Lykke; Nissen, Mogens Holst

    2013-01-01

    PURPOSE: To examine the association between age-related changes in the T-cell compartment and prevalence of age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: A total of 117 AMD cases and 106 controls were included prospectively. METHODS: Fresh-drawn peripheral blood...... levels of circulating aged CD56(+) CD28(-) T cells in patients with AMD. Although this supports the notion of AMD as a systemic disease, it also suggests that the adaptive immune system is implicated in its pathogenesis....

  11. Ranibizumab in neovascular age-related macular degeneration: a 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Cvetkova NP

    2016-06-01

    Full Text Available Nadezhda P Cvetkova, Kristina Hölldobler, Philipp Prahs, Viola Radeck, Horst Helbig, David Märker Department of Ophthalmology, University of Regensburg, Regensburg, Germany Purpose: Our aim was to evaluate an optical coherence tomography (OCT and visual acuity (VA-guided, variable-dosing regimen with intravitreal ranibizumab injection for treating patients with neovascular age-related macular degeneration (AMD from 2007 to 2012. Design: This was a retrospective clinical study of 5 years follow-up in a tertiary eye center. Patients and methods: In this study, 66 patients with neovascular AMD (mean age of 74 years, SD 8.7 years were included. We investigated the development of best-corrected visual acuity (BCVA, the number of intravitreal injections, and the central retinal thickness measured with OCT (OCT Spectralis over 5 years of intravitreal treatment. Results: The mean number of intravitreal ranibizumab injections over 5 years was 8.8. The mean BCVA before therapy was 0.4 logarithm of the minimum angle of resolution (logMAR. After 5 years of therapy, the mean BCVA was 0.6 logMAR. In all, 16% of treated patients had stable VA over 5 years and 10% of study eyes approved their VA. The mean OCT-measured central retinal thickness at the beginning of this study was 295 µm; after 5 years of treatment, the mean central retinal thickness was 315 µm. There was an increase in central retinal thickness in 47.5% of examined eyes. Conclusion: Other studies showed VA improvement in OCT-guided variable-dosing regimens. Our study revealed a moderate decrease in VA after a total mean injection number as low as 8.8 injections over 5 years. In OCT, an increase in central retinal thickness over 5 years could be observed. Probably, this is due to deficient treatment when comparing the total injection number to other treatment regimens. Anti-VEGF therapy helps to keep the VA stable for a period of time, but cannot totally stop the progression of

  12. [Age-related macular degeneration – a challenge for public health care].

    Science.gov (United States)

    Mantel, Irmela

    2016-01-01

    Age-related macular degeneration (AMD) is the predominant cause of legal blindness in the population over 50 years of age. The disorder shows exponentially increasing prevalence with age, and the late forms with their vision threatening evolution are found in approximately one third of cases. The late AMD may be purely atrophic and so far untreatable. Or it may be neovascular and exudative, for which medical treatment is available, consisting of repetitive intravitreous injections of Anti-VEGF molecules. The treatment is highly effective in blocking the growth of the pathological vessels and allowing resolution of the accompanying edema. Visual improvement is variable but often very meaningful for the patients. However, the final visual level depends mostly on early intervention. Thus, screening for the first signs of neovascular AMD is crucial for the endresult. However, the repetitive intraocular injections are an important burden for the patients. Due to the high patient numbers, the chronic care management with steadily adding new patients is a major challenge for treating institutions. Limited resources may put patients at risk of undertreatment with resulting visual loss. Various strategies have been developed to cope with the burden. In addition, the financial cost is high for the health care system. On the other hand, timely and ongoing treatment is the best investment to achieve meaningful visual improvement, which is extremely important for the quality of life and autonomy of the patients. Side effects of the treatment are limited and mostly procedure related. Systemic side effects are possible but despite the large studies not conclusive. However, care must be taken in cases of high cardiovascular risk, as thromboembolic risk increase may rarely happen. So far unsolved problems include the long term visual results, the degree of reversibility of neovascularization, and the missing treatment options of atrophic AMD. Basic and clinical research on various

  13. A simple technique for treating age-related macular degeneration with external beam radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To develop a simple external beam photon radiotherapy technique to treat age-related macular degeneration without the need for simulation, planning computed tomography (CT) or computer dosimetry. Methods and Materials: The goal was to enable the treatment to be set up reliably on the treatment machine on Day 1 with the patient supine in a head cast without any prior planning. Using measurements of ocular globe topography from Karlsson et al. (Int J Radiat Oncol Biol Phys 1996; 33: 705-712), we chose a point 1.5 cm behind the anterior surface of the upper eyelid (ASUE) as the isocentre of a half-beam, blocked, 5.0 x 3.0-cm, angled lateral field to treat the involved eye. This would position the isocentre about 0.5 cm behind the posterior surface of the lens, and a little over 1 cm in front of the macula, according to Karlsson et al. The setup requires initial adjustment of the gantry from horizontal (to account for any asymmetry of position of the eyes), then angling 15 deg. posteriorly to avoid the contralateral eye. Finally, the couch is raised to position the isocentre 1.5 cm behind the ASUE. Results: To verify the applicability of the technique, we performed CT and computer dosimetry on the first 11 eyes so treated. Our CT measurements were in good agreement with Karlsson et al. The lens dose was < 5% and the macula was within the 95% isodose curve in each case (6-MV linac). Treatment setup time is approximately 10 min each day. The 11 patients were treated with 5 x 2.00 Gy (2 patients) or 5 x 3.00 Gy (9 patients), and subjective response on follow-up over 1 to 12 months (median 4 months) was comparable to previously reported results, with no significant acute side effects. Conclusion: Our technique is easy to set up and reliably treats the macula, with sparing of the lens and contralateral eye. It enables treatment to commence rapidly and cost-effectively without the need for simulation or CT computer planning

  14. Evaluation of variants in the selectin genes in age-related macular degeneration

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    Wang Kai

    2011-04-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is a common disease of the elderly that leads to loss of the central visual field due to atrophic or neovascular events. Evidence from human eyes and animal models suggests an important role for macrophages and endothelial cell activation in the pathogenesis of AMD. We sought to determine whether common ancestral variants in genes encoding the selectin family of proteins are associated with AMD. Methods Expression of E-selectin, L-selectin and P-selectin was examined in choroid and retina by quantitative PCR and immunofluorescence. Samples from patients with AMD (n = 341 and controls (n = 400 were genotyped at a total of 34 SNPs in the SELE, SELL and SELP genes. Allele and genotype frequencies at these SNPs were compared between AMD patients and controls as well as between subtypes of AMD (dry, geographic atrophy, and wet and controls. Results High expression of all three selectin genes was observed in the choroid as compared to the retina. Some selectin labeling of retinal microglia, drusen cores and the choroidal vasculature was observed. In the genetic screen of AMD versus controls, no positive associations were observed for SELE or SELL. One SNP in SELP (rs3917751 produced p-values SELE, two in SELL, and three in SELP produced p-values SELP (rs3917751 produced a statistically significant p-value (p = 0.0029. Conclusions This genetic screen did not detect any SNPs that were highly associated with AMD affection status overall. However, subtype analysis showed that a single SNP located within an intron of SELP (rs3917751 is statistically associated with dry AMD in our cohort. Future studies with additional cohorts and functional assays will clarify the biological significance of this discovery. Based on our findings, it is unlikely that common ancestral variants in the other selectin genes (SELE and SELL are risk factors for AMD. Finally, it remains possible that sporadic or rare

  15. Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

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    Hartnett ME

    2011-09-01

    Full Text Available Haibo Wang1, Erika S Wittchen2, M Elizabeth Hartnett11Department of Ophthalmology, John A Moran Eye Center, University of Utah, Salt Lake City, UT; 2Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAAbstract: Neovascular age-related macular degeneration (AMD is a leading cause of central visual acuity loss in a growing segment of the population, those over the age of 60 years. Treatment has improved over the last decade, with the availability of agents that inhibit the bioactivity of vascular endothelial growth factor (VEGF, but it is still limited, because of tachyphylaxis and potential risk and toxicity of anti-VEGF agents. The authors have sought to understand the mechanisms of choroidal endothelial cell (CEC activation and transmigration of the retinal pigment epithelium (RPE and of RPE barrier dysfunction, events preceding vision-threatening neovascular AMD. The authors developed physiologically relevant human RPE and CEC coculture and transmigration models that have been important in helping to understand causes of events in human neovascular AMD. The authors can control for interactions between these cells and can separately assess activation of signaling pathways in each cell type relevant during CEC transmigration. Using these models, it was found that VEGF, particularly the cell-associated VEGF splice variant VEGF189, accounts for about 40% of CEC transmigration across the RPE. This percentage is in the range of similar reports following clinical inhibition of VEGF in neovascular AMD. RPE VEGF189 working through CEC VEGF receptor 2 activates the small guanosine triphosphatase (GTPase of the Rho family, Rac1, in CECs, which in turn facilitates CEC transmigration. Conversely, inhibition of Rac1 activity prevents CEC transmigration. Once activated, Rac1 aggregates with subunits of nicotinamide adenine dinucleotide phosphate (NADPH oxidase, resulting in the generation of reactive

  16. Development of gene therapy for treatment of age-related macular degeneration.

    Science.gov (United States)

    Askou, Anne Louise

    2014-07-01

    Intraocular neovascular diseases are the leading cause of blindness in the Western world in individuals over the age of 50. Age-related macular degeneration (AMD) is one of these diseases. Exudative AMD, the late-stage form, is characterized by abnormal neovessel development, sprouting from the choroid into the avascular subretinal space, where it can suddenly cause irreversible damage to the vulnerable photoreceptor (PR) cells essential for our high-resolution, central vision. The molecular basis of AMD is not well understood, but several growth factors have been implicated including vascular endothelial growth factor (VEGF), and the advent of anti-VEGF therapy has markedly changed the outcome of treatment. However, common to all current therapies for exudative AMD are the complications of repeated monthly intravitreal injections, which must be continued throughout one's lifetime to maintain visual benefits. Additionally, some patients do not benefit from established treatments. Strategies providing long-term suppression of inappropriate ocular angiogenesis are therefore needed, and gene therapy offers a potential powerful technique. This study aimed to develop a strategy based on RNA interference (RNAi) for the sustained attenuation of VEGF. We designed a panel of anti-VEGF short hairpin RNAs (shRNA), and based on the most potent shRNAs, microRNA (miRNA)-mimicked hairpins were developed. We demonstrated an additive VEGF silencing effect when we combined the miRNAs in a tricistronic miRNA cluster. To meet the requirements for development of medical treatments for AMD with long-term effects, the shRNA/miRNA is expressed from vectors based on adeno-associated virus (AAV) or lentivirus (LV). Both vector systems have been found superior in terms of transduction efficiency and persistence in gene expression in retinal cells. The capacity of AAV-encoded RNAi effector molecules to silence endogenous VEGF gene expression was evaluated in mouse models, including the model

  17. Intravitreal ranibizumab and bevacizumab therapy for choroidal neovascularization in age-related macular degeneration with extensive pre-existing geographic atrophy

    OpenAIRE

    Miguel Hage Amaro; Aaron Brock Roller

    2012-01-01

    PURPOSE: To report the response of choroidal neovascularization to intravitreal ranibizumab or bevacizumab treatment in the setting of age-related macular degeneration with extensive pre-existing geographic atrophy of the retinal pigment epithelium. METHODS: This is a retrospective case series of 11 eyes in ten consecutive patients retrieved from a photographic database. The patients were treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration with pre-existin...

  18. The effect of intravitreal administration of bevacizumab on macular edema and visual acuity in age-related macular degeneration with subfoveolar choroidal neovascularisation

    OpenAIRE

    Ristić Dragana; Vukosavljević Miroslav; Draganić Biljana; Cerović Vesna; Petrović Nenad; Janićijević-Petrović Mirjana

    2013-01-01

    Background/Aim. Age-related macular degeneration (AMD) is a leading cause of the loss of central visual acuity in population older than 70 years. We can distinguish wet and dry form of AMD. The aim of the study was to present our early results in treatment of the wet (neovascular) form of AMD with intravitreal administration of bevacizumab. Methods. The study included 39 patients. Each patient underwent a complete ophthalmological examination, fluorescein angiography (FA) and optical co...

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

    Directory of Open Access Journals (Sweden)

    Vasileios Peponis

    2010-07-01

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

  20. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    OpenAIRE

    K. A. Mirzabekova

    2015-01-01

    Common pathogenic aspects of age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma wi...

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

    OpenAIRE

    Robison, Craig D.; Jivrajka, Renu V.; Bababeygy, Simon R.; Fink, Wolfgang; Sadun, Alfredo A; Sebag, J.

    2011-01-01

    Background/aims: With the increased efficacy of current therapy for wet age-related macular degeneration (AMD), better ways to detect wet AMD are needed. This study was designed to test the ability of three-dimensional contrast threshold Amsler grid (3D-CTAG) testing to distinguish wet AMD from dry AMD. Methods: Conventional paper Amsler grid and 3D-CTAG tests were performed in 90 eyes: 63 with AMD (34 dry, 29 wet) and 27 controls. Qualitative comparisons were based upon the three-dimensi...

  2. Optical Coherence Tomography Updates on Clinical and Technical Developments. Age-Related Macular Degeneration: Drusen and Geographic Atrophy

    Science.gov (United States)

    Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Holz, Frank G.

    Age-related macular degeneration (AMD) is a complex disease with both genetic and environmental factors influencing its development. With the advent of high-resolution OCT imaging, the characterization of drusen in AMD has become possible. The in vivo morphologic characteristics imaged with SD-OCT may represent distinct subclasses of drusen variants, may relate closely to ultrastructural drusen elements identified in donor eyes, and may be useful imaging biomarkers for disease severity or risk of progression [Khanifar et al. Ophthalmology 115(11):1883-1890, 2008].

  3. Emerging therapies for the treatment of wet age-related macular degeneration--VEGF Trap-Eye.

    Science.gov (United States)

    Rejdak, Robert; Szkaradek, Małgorzata; Grieb, Paweł; Jünemann, Anselm G M

    2011-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. The most severe form of this disease is exudative AMD. It accounts for 10% of cases of AMD and is responsible for approximately 90% cases of severe vision loss due to AMD. Anti-vascular endothelial growth factor (VEGF) therapy changed the standard-of-care for this blinding disease. This article presents one promising new drug for the treatment of exudative AMD--VEGF Trap-Eye. PMID:22384659

  4. Dosimetry characterization of a multibeam radiotherapy treatment for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Choonsik; Chell, Erik; Gertner, Michael; Hansen, Steven; Howell, Roger W.; Hanlon, Justin; Bolch, Wesley E. [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Florida 32611 (United States); Oraya Therapeutics, Inc., Newark, California 94560 (United States); Department of Radiology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103 (United States); Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Florida 32611 (United States); Departments of Nuclear and Radiological and Biomedical Engineering, University of Florida, Gainesville, Florida 32611 (United States)

    2008-11-15

    Age-related macular degeneration (ARMD) is a major health problem worldwide. Advanced ARMD, which ultimately leads to profound vision loss, has dry and wet forms, which account for 20% and 80% of cases involving severe vision loss, respectively. A new device and approach for radiation treatment of ARMD has been recently developed by Oraya Therapeutics, Inc. (Newark, CA). The goal of the present study is to provide a initial dosimetry characterization of the proposed radiotherapy treatment via Monte Carlo radiation transport simulation. A 3D eye model including cornea, anterior chamber, lens, orbit, fat, sclera, choroid, retina, vitreous, macula, and optic nerve was carefully designed. The eye model was imported into the MCNPX2.5 Monte Carlo code and radiation transport simulations were undertaken to obtain absorbed doses and dose volume histograms (DVH) to targeted and nontargeted structures within the eye. Three different studies were undertaken to investigate (1) available beam angles that maximized the dose to the macula target tissue, simultaneously minimizing dose to normal tissues, (2) the energy dependency of the DVH for different x-ray energies (80, 100, and 120 kVp), and (3) the optimal focal spot size among options of 0.0, 0.4, 1.0, and 5.5 mm. All results were scaled to give 8 Gy to the macula volume, which is the current treatment requirement. Eight beam treatment angles are currently under investigation. In all eight beam angles, the source-to-target distance is 13 cm, and the polar angle of entry is 30 degree sign from the geometric axis of the eye. The azimuthal angle changes in eight increments of 45 degree sign in a clockwise fashion, such that an azimuthal angle of 0 degree sign corresponds to the 12 o'clock position when viewing the treated eye. Based on considerations of nontarget tissue avoidance, as well as facial-anatomical restrictions on beam delivery, treatment azimuthal angles between 135 degree sign and 225 degree sign would be

  5. Dosimetry characterization of a multibeam radiotherapy treatment for age-related macular degeneration

    International Nuclear Information System (INIS)

    Age-related macular degeneration (ARMD) is a major health problem worldwide. Advanced ARMD, which ultimately leads to profound vision loss, has dry and wet forms, which account for 20% and 80% of cases involving severe vision loss, respectively. A new device and approach for radiation treatment of ARMD has been recently developed by Oraya Therapeutics, Inc. (Newark, CA). The goal of the present study is to provide a initial dosimetry characterization of the proposed radiotherapy treatment via Monte Carlo radiation transport simulation. A 3D eye model including cornea, anterior chamber, lens, orbit, fat, sclera, choroid, retina, vitreous, macula, and optic nerve was carefully designed. The eye model was imported into the MCNPX2.5 Monte Carlo code and radiation transport simulations were undertaken to obtain absorbed doses and dose volume histograms (DVH) to targeted and nontargeted structures within the eye. Three different studies were undertaken to investigate (1) available beam angles that maximized the dose to the macula target tissue, simultaneously minimizing dose to normal tissues, (2) the energy dependency of the DVH for different x-ray energies (80, 100, and 120 kVp), and (3) the optimal focal spot size among options of 0.0, 0.4, 1.0, and 5.5 mm. All results were scaled to give 8 Gy to the macula volume, which is the current treatment requirement. Eight beam treatment angles are currently under investigation. In all eight beam angles, the source-to-target distance is 13 cm, and the polar angle of entry is 30 degree sign from the geometric axis of the eye. The azimuthal angle changes in eight increments of 45 degree sign in a clockwise fashion, such that an azimuthal angle of 0 degree sign corresponds to the 12 o'clock position when viewing the treated eye. Based on considerations of nontarget tissue avoidance, as well as facial-anatomical restrictions on beam delivery, treatment azimuthal angles between 135 degree sign and 225 degree sign would be available

  6. Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    P William Conrad

    2008-06-01

    Full Text Available P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15 if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153 and 20/100 at 8 weeks (p = 0.0027. Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005. By masked OCT grading, macular fluid was resolved in 10/15 (66.7% and 11/15 (73.3% eyes at 4 and 8 weeks, respectively, and 3/15 (20% eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomography

  7. Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population

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    Basheer K

    2015-05-01

    Full Text Available Khadijah Basheer, Evelyn Mensah, Tina Khanam, Neda Minakaran Ophthalmology Department, Central Middlesex Hospital, London, UK Aim: To compare the visual outcomes of an urban population with age-related macular degeneration (AMD undergoing ranibizumab monotherapy to the results from major clinical trials.Procedures: Prospective data was collected from 164 wet AMD patients receiving intravitreal ranibizumab. Visual acuities were obtained with the Early Treatment Diabetic Retinopathy Study chart. All patients underwent a loading phase of three monthly treatments of ranibizumab. Patients were monitored monthly using a retreatment criterion. Treatment was further individualized by sequentially lengthening follow-up intervals when stable.Results: At 12 and 24 months, respectively, the percentage of eyes that maintained vision was 91% and 88.6%. We found that 20.3% of eyes had improved vision at 12 months and 20% at 24 months. At 12 months, 8.3% of eyes’ vision worsened and 12% worsened at 24 months.Conclusion: Individualized ranibizumab monotherapy is effective in preserving vision in wet AMD and follows the same trends as the pivotal trials. Keywords: visual acuity, comparison of age-related macular degeneration treatment trials, choroidal neovascular membrane

  8. Increased Expression of CD200 on Circulating CD11b+ Monocytes in Patients with Neovascular Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads K; Hviid, Thomas V F; Sørensen, Torben Lykke

    2013-01-01

    neovascular age-related macular degeneration (AMD) and 44 age-matched controls without AMD. METHODS: The participants were aged 60 years or older, had no history of immune dysfunction or cancer, and were not receiving immune-modulating therapy. All participants were subjected to a structured interview, and...... detailed retinal imaging was performed: fundus autofluorescence imaging, digital color fundoscopy, and spectral-domain optical coherence tomography. Fluorescein and indocyanine green angiography were performed in patients with suspected neovascular AMD. Visual acuity was measured in both eyes. Fresh venous......: Patients with neovascular AMD had a higher percentage of CD11b+CD200+ monocytes and CD200+ monocytes compared with controls. Multiple regression analysis revealed that the intergroup differences observed were independent of age. Moreover, an age-related increment in CD200 expression on monocytes was...

  9. Repeatability of retinal thickness and volume metrics in neovascular age-related macular degeneration using the topcon 3doct-1000

    Directory of Open Access Journals (Sweden)

    Vikas Tah

    2014-01-01

    Full Text Available Introduction: Optical coherence tomography (OCT is a commonly used imaging modality that provides detailed cross-sectional retinal images. This has revolutionised management of neovascular age-related macular degeneration. The need for repeated anti-vascular endothelial growth factor injections has led to therapy being delivered using OCT-guided retreatment strategies with both qualitative OCT features of disease activity (e.g. macular fluid and changes in retinal thickness as triggers for retreatment The purpose of this study is to determine the intra-session repeatability of retinal thickness and volume measurements using the Topcon 3DOCT-1000 spectral-domain optical coherence tomography (SDOCT device in patients with neovascular age-related macular degeneration (nAMD. This is the largest study to date looking specifically at the Topcon 3DOCT-1000. Materials and Methods: Two SDOCT raster scans were performed by the same blinded observer in the same sitting in consecutive patients attending for nAMD treatment as part of standard validation of a new device. Retrospective analysis was undertaken, with retinal thickness and volume measurements automatically calculated by the onboard software for each Early Treatment of Diabetic Retinopathy Study subfield for each scan. Bland-Altman methods of analysis were used to assess repeatability. Results: Data from the 73 patients were analyzed with a mean age of 78 years (standard deviation 8. The 95% coefficient of repeatability (CR was 64 μm and 0.050 mm 3 for retinal thickness and volume respectively in the central 1 mm macular subfield. The CR did not exceed 85 μm (0.30 mm 3 in any subfield. The revised CR for retinal thickness and volume for the subgroup of 37 patients with no segmentation error in the central 1 mm subfield was 53 μm and 0.050 mm 3 respectively. Discussion : We report relatively modest intra-sessional repeatability of SDOCT retinal thickness and volume metrics in patients with n

  10. Long-term longitudinal study of patients treated with ranibizumab for neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Sander, Birgit

    2014-01-01

    PURPOSE OF REVIEW: To review the current literature regarding long-term treatment beyond 2 years with anti-vascular endothelial growth factor (VEGF) inhibition for neovascular age-related macular degeneration (nv-AMD). RECENT FINDINGS: Only few studies of anti-VEGF treatment for nv-AMD exist beyond...... 2 years, and the number of patients followed for 4 years or longer is small. The results of studies show that the majority of patients with nv-AMD can preserve visual acuity compared with baseline, subgroups reveal large variations in visual benefit. Approximately 20-30% of patients seem to respond...... for further improvement. Close follow-up to detect recurrent activity of nv-AMD and activity in fellow eye is important. Definitive evidence of systemic side-effects is lacking, but long-term VEGF inhibition seems to be tolerated well with few ocular and systemic complications. SUMMARY: The majority...

  11. Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography

    Science.gov (United States)

    Baumann, Bernhard; Götzinger, Erich; Pircher, Michael; Sattmann, Harald; Schütze, Christopher; Schlanitz, Ferdinand; Ahlers, Christian; Schmidt-Erfurth, Ursula; Hitzenberger, Christoph K.

    2010-11-01

    We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures' tissue-inherent polarization properties.

  12. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    Science.gov (United States)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  13. Interleukin-17 Retinotoxicity Is Prevented by Gene Transfer of a Soluble Interleukin-17 Receptor Acting as a Cytokine Blocker: Implications for Age-Related Macular Degeneration

    OpenAIRE

    Ardeljan, Daniel; Wang, Yujuan; Park, Stanley; Shen, DeFen; Chu, Xi Kathy; Yu, Cheng-Rong; Abu-Asab, Mones; Tuo, Jingsheng; Eberhart, Charles G.; Olsen, Timothy W.; Mullins, Robert F; White, Gary; Wadsworth, Sam; Scaria, Abraham; Chan, Chi-Chao

    2014-01-01

    Age-related macular degeneration (AMD) is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A) and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subseq...

  14. Comparison of the effect between pegaptanib and ranibizumab on exudative age-related macular degeneration with small lesion size

    Directory of Open Access Journals (Sweden)

    Fujihara M

    2012-03-01

    Full Text Available Yoshihiro Nishimura1,2, Maiko Taguchi1, Takafumi Nagai1, Masashi Fujihara1,2, Shigeru Honda2, Mamoru Uenishi11Department of Ophthalmology, Mitsubishi Kobe Hospital, Kobe, Japan; 2Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, JapanPurpose: To compare the effect of pegaptanib versus ranibizumab on exudative age-related macular degeneration (AMD with small lesion size.Methods: This is a retrospective study of 81 eyes from 78 patients with exudative AMD treated and followed up over 12 months. Patients with baseline best corrected visual acuity (BCVA under 20/400 and with a greatest linear dimension of lesion over 4500 µm were excluded from the study. Twenty-six eyes from 25 patients were treated with three consecutive intravitreal injections of pegaptanib (IVP group and 55 eyes from 54 patients were treated with three consecutive ranibizumab injections (IVR group. Each therapy was repeated as needed. The alteration in BCVA was evaluated in the IVP and IVR groups.Results: No differences were detected in baseline parameters between the IVP and IVR groups. The mean BCVA (logMAR at month 1, 3, 6 and 12 after the initial treatment was improved from baseline in the IVP group (-0.095, -0.17, -0.18 and -0.18, respectively and in the IVR group (-0.077, -0.15, -0.17 and -0.11, respectively, which was statistically significant. There was no difference in the change in mean BCVA between IVP and IVR groups at the same time periods.Conclusions: The visual outcome of IVP was equivalent with IVR in exudative AMD with small lesion size.Keywords: pegaptanib, ranibizumab, age-related macular degeneration, small lesion size

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

    Science.gov (United States)

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs. PMID:27010695

  16. Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

    Science.gov (United States)

    Gohil, Rishma; Crosby-Nwaobi, Roxanne; Forbes, Angus; Burton, Ben J; Hykin, Philip; Sivaprasad, Sobha

    2016-01-01

    Context Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD) remains unclear. Aims The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting. Settings and design A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact. Materials and methods A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8) and the patients’ demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined. Results The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8), health-related quality of life (EQ-5D-3L), and duration of AMD. Visual acuity changes were rated as less important than one would have expected. Conclusion The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment. PMID:27307715

  17. 6-weekly bevacizumab versus 4-weekly ranibizumab for neovascular age-related macular degeneration: a 2-year outcome

    Directory of Open Access Journals (Sweden)

    Patrick J Chiam

    2016-04-01

    Full Text Available AIM: To compare visual acuity and central macular thickness (CMT changes in neovascular age related macular degeneration patients treated with either 6 weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis. METHODS: Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits. Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on the reduction of >5 letters in the best-corrected visual acuity (BCVA, the presence of retinal fluid on optical coherence tomography (OCT or new retinal haemorrhage. RESULTS: Visual acuity at 2y bevacizumab patients gained 7.0 letters and ranibizumab 9.2 (P=0.31, 95% CI -6.4 to 2.0. At 2y 86% of bevacizumab and 94% ranibizumab patients had not lost 15 letters or more (P=0.13. Mean CMT decreased at 2y bevacizumab by 146 µm, ranibizumab 160 µm (P=0.72. Mean number of injections was at 2y bevacizumzb 11.9, ranibizumab 10.3 (P=0.023. CONCLUSION: Bevacizumab 6 weekly on an as required basis was not demonstrably non-inferior to ranibizumab 4 weekly pro re nata (prn in terms of BCVA and change in CMT. In the bevacizumab group, one more injection was required in the second year compared to the ranibizumab group.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-12-01

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

  20. Quantitative analysis of cone photoreceptor distribution and its relationship with axial length, age, and early age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Ryo Obata

    Full Text Available PURPOSE: It has not been clarified whether early age-related macular degeneration (AMD is associated with cone photoreceptor distribution. We used adaptive optics fundus camera to examine cone photoreceptors in the macular area of aged patients and quantitatively analyzed its relationship between the presence of early AMD and cone distribution. METHODS: Sixty cases aged 50 or older were studied. The eyes were examined with funduscopy and spectral-domain optical coherence tomography to exclude the eyes with any abnormalities at two sites of measurement, 2° superior and 5° temporal to the fovea. High-resolution retinal images with cone photoreceptor mosaic were obtained with adaptive optics fundus camera (rtx1, Imagine Eyes, France. After adjusting for axial length, cone packing density was calculated and the relationship with age, axial length, or severity of early AMD based on the age-related eye disease study (AREDS classification was analyzed. RESULTS: Patient's age ranged from 50 to 77, and axial length from 21.7 to 27.5 mm. Mean density in metric units and that in angular units were 24,900 cells/mm2, 2,170 cells/deg2 at 2° superior, and 18,500 cells/mm2, 1,570 cels/deg2 at 5° temporal, respectively. Axial length was significantly correlated with the density calculated in metric units, but not with that in angular units. Age was significantly correlated with the density both in metric and angular units at 2° superior. There was no significant difference in the density in metric and angular units between the eyes with AREDS category one and those with categories two or three. CONCLUSION: Axial length and age were significantly correlated with parafoveal cone photoreceptor distribution. The results do not support that early AMD might influence cone photoreceptor density in the area without drusen or pigment abnormalities.

  1. What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD?

    Directory of Open Access Journals (Sweden)

    Willich, Stefan N.

    2006-12-01

    Full Text Available Background: The cataract (Cataracta senilis is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing number of patients will suffer from cataract and AMD at the same time. This coincidence leads to a greater interest in the question of a mutual influence of both diseases, respectively their therapies, on each other. Objectives: The aim of this report was the evaluation of the medical and health economic effects of cataract operations on the development and progression of an age related macular degeneration (AMD. It was differentiated between first manifestations of AMD, progression of early stages of AMD and influence on further impairment in late stages of AMD. Methods: The relevant publications for this report were identified by DIMDI via structured database enquiry as well as common, self-made enquiry and were evaluated, based on the criteria of evidence based medicine. The present report included German and English literature published since 1983. Results: The database enquiry generated a record of 2769 issue-related publications. Eight medical publications were eligible for analysis in the course of the present HTA report. No relevant studies on health economical, ethical, social or legal issues could be included. Three epidemiological cohort studies provided some evidence for a promoting influence of cataract extractions on the progression of early types of AMD. Two of the epidemiological studies assessed the risk of first manifestation of AMD after cataract extraction. Both came up with up with increased incidences that did not reach statistical

  2. IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

    DEFF Research Database (Denmark)

    Ross, Christian; Engler, Claus Bødker; Sander, Birgit; Bendtzen, Klaus

    2002-01-01

    We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

  3. Reducing the Genetic Risk of Age-Related Macular Degeneration With Dietary Antioxidants, Zinc, and omega-3 Fatty Acids The Rotterdam Study

    NARCIS (Netherlands)

    L. Ho; R. van Leeuwen; J.C.M. Witteman; C.M. van Duijn; A.G. Uitterlinden; A. Hofman; P.T.V.M. de Jong; J.R. Vingerling; C.C.W. Klaver

    2011-01-01

    Objective: To investigate whether dietary nutrients can reduce the genetic risk of early age-related macular degeneration (AMD) conferred by the genetic variants CFH Y402H and LOC387715 A69S in a nested case-control study. Methods: For 2167 individuals (>= 55 years) from the population-based Rotterd

  4. Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study

    Science.gov (United States)

    To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. This is a multice...

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Liu Melissa M

    2012-08-01

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

  7. The effect of intravitreal administration of bevacizumab on macular edema and visual acuity in age-related macular degeneration with subfoveolar choroidal neovascularisation

    Directory of Open Access Journals (Sweden)

    Ristić Dragana

    2013-01-01

    Full Text Available Background/Aim. Age-related macular degeneration (AMD is a leading cause of the loss of central visual acuity in population older than 70 years. We can distinguish wet and dry form of AMD. The aim of the study was to present our early results in treatment of the wet (neovascular form of AMD with intravitreal administration of bevacizumab. Methods. The study included 39 patients. Each patient underwent a complete ophthalmological examination, fluorescein angiography (FA and optical coherence tomography (OCT. All the patients received 1.25 mg of intravitreal bevacizumab (0.05 mL of commercial phial of Avastin®. The total of three doses was given with a one-month interval between doses. Results. Among 39 patients, 24 were women and 15 men. The average best corrected visual acuity (BCVA was improved from 0.09 before the therapy to 0.24 after the administration of all the three doses of bevacizumab (p < 0.001. The average central macular thickness (CMT measured by OCT was improved from 474 μm in the beginning to 341 μm after the administration of all the three doses of the drug (p < 0.001. There were no side effects. Conclusions. Our short-term experience indicates that intravitreal administration of three doses of bevacizumab in one-month intervals between the doses leads to a significant reduction of macular edema and improvement of BCVA in patients with neovascular AMD.

  8. Macular degeneration (image)

    Science.gov (United States)

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

  9. Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group.

    Science.gov (United States)

    1990-06-01

    The Age-Related Macular Degeneration Study-Krypton Laser (AMDS-K) is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with macular degeneration that have either choroidal neovascularization 1 to 199 microns from the center of the foveal avascular zone or choroidal neovascularization 200 microns or farther from the foveal avascular zone center with blood and/or blocked fluorescence extending within 200 microns of the foveal avascular zone center. Recruitment ended in December 1987 after 247 patients had been assigned to photocoagulation and 249 patients had been assigned to no treatment. At 3 years after randomization, 49% (86/174) of treated eyes, in contrast to 58% (98/169) of untreated eyes, had lost six or more lines of visual acuity. The average visual acuity of treated and untreated eyes at that time was 20/200 and 20/250, respectively. The benefit of laser treatment was largest among patients without evidence of hypertension and diminished to no apparent benefit among patients who had highly elevated blood pressure and/or used antihypertensive medication. Treatment of lesions meeting the AMDS-K eligibility criteria in eyes of patients with no hypertension is recommended. However, treatment cannot be recommended uniformly for patients with definite hypertension having lesions similar to those of patients enrolled in the AMDS-K. PMID:1693496

  10. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    Science.gov (United States)

    Smith, Theresa Marie

    2008-01-01

    One in eight Americans aged 65 and older has an eye disease resulting in low vision, and more women than men are visually impaired, mainly because women live longer. Age-related visual impairments are an indicator of a decline in activities of daily living and self-help skills. The top eye conditions that affect older adults are macular…

  11. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Balaratnasingam C

    2015-12-01

    Full Text Available Chandrakumar Balaratnasingam,1–3 Elona Dhrami-Gavazi,1,2,4 Jesse T McCann,1,2,4,5 Quraish Ghadiali,1,2 K Bailey Freund1,2,4,5 1Vitreous-Retina-Macula Consultants of New York, NY, USA; 2LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY, USA; 3Centre for Ophthalmology and Visual Sciences, Lions Eye Institute, University of Western Australia, Perth, WA, Australia; 4Department of Ophthalmology, Edward S Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, New York University School of Medicine, New York, NY, USA Abstract: Choroidal neovascularization (CNV due to age-related macular degeneration (AMD is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®, initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to

  12. Effect of ranibizumab on serous and vascular pigment epithelial detachments associated with exudative age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Panos GD

    2013-07-01

    Full Text Available Georgios D Panos,1 Zisis Gatzioufas,1 Ioannis K Petropoulos,1 Doukas Dardabounis,2 Gabriele Thumann,1 Farhad Hafezi11Department of Ophthalmology, Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland; 2Department of Ophthalmology, University Hospital of Alexandroupolis, GreecePurpose: To report the effect of intravitreal ranibizumab therapy for serous and vascular pigment epithelial detachments (PED associated with choroidal neovascularisation (CNV secondary to age-related macular degeneration (AMD.Methods: In a prospective study, best-corrected visual acuity (BCVA and optical coherence tomography (OCT data were collected for 62 eyes of 62 patients, with serous or vascular PED associated with CNV secondary to AMD. Intravitreal ranibizumab 0.5 mg was administered with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to the retreatment criteria of the PrONTO study. The change in visual acuity and PED height from baseline to month 12 after the first injection was determined.Results: Sixty-one eyes of 61 patients (one of the patients developed retinal pigment epithelial tear and was excluded from the study were assessed at the 12-month follow-up examination. There were two types of PED, including vascular PED in 32 patients (Group A and serous PED (Group B in 29 patients. The mean improvement of mean BCVA from baseline to 12 months was 0.09 logMAR (Logarithm of the Minimum Angle of Resolution in Group A and 0.13 logMAR in Group B. Both groups showed significant improvement of the mean BCVA 12 months after the first injection compared with the baseline value (P < 0.05. In relation to the PED height, the mean decrease of mean PED height from baseline to 12 months was 135 µm in Group A and 180 µm in Group B. Both groups showed significant reduction of the PED height during the follow-up period (P < 0.01. The PED anatomical response

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

    Directory of Open Access Journals (Sweden)

    Ba J

    2015-09-01

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

  14. Clinical course over two to six years of age-related macular degeneration with or without radiation

    International Nuclear Information System (INIS)

    We previously reported about the long-term outcome as long as three years after radiation therapy for choroidal neovascularization secondary to age-related macular degeneration (AMD). Though MPS (Macular Photocoagulation Study) Group reported the long-term natural course of AMD, such reports have not been provided concerned about Japanese AMD patients. Furthermore, there is not report that revealed the course of AMD with radiation therapy more than three years. We evaluated the long-term natural course and long-term effect of low-dose radiation on AMD. The fundus ophthalmoscopic evaluation and visual outcome were compared retrospectively among control group and two treated groups; seven eyes received 10 Gy, and eight eyes 20 Gy. The control group consisted of 10 eyes without treatment. All patients were followed at least four years, and the average follow-up duration was 6.56 years. The course of median visual acuity without treatment showed the similar result to that of MPS Group's report. In control group, visual acuity (VA) after four years was better in no eyes, unchanged in two eyes, and worse in eight eyes; in treated group, better in four eyes, unchanged in one eye, and worse in ten eyes. After four years VA was kept 20/200 or higher in 2 eyes without treatment, 4 eyes with 10 Gy, and 4 eyes with 20 Gy of radiation. Then maximum VA was 20/125 with no treatment, and 20/50 with radiation therapy. The natural course of the AMD of Japanese patients showed similar results to US patients. All eyes of AMD withort treatment got worse in VA, and some showed better outcome with radiation therapy; but it was not statistically significant. (author)

  15. Clinical course over two to six years of age-related macular degeneration with or without radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kameda, Takanori; Noami, Sachiyo; Akita, Joe [Kyoto Univ. (Japan). Graduate School of Medicine] (and others)

    2002-10-01

    We previously reported about the long-term outcome as long as three years after radiation therapy for choroidal neovascularization secondary to age-related macular degeneration (AMD). Though MPS (Macular Photocoagulation Study) Group reported the long-term natural course of AMD, such reports have not been provided concerned about Japanese AMD patients. Furthermore, there is not report that revealed the course of AMD with radiation therapy more than three years. We evaluated the long-term natural course and long-term effect of low-dose radiation on AMD. The fundus ophthalmoscopic evaluation and visual outcome were compared retrospectively among control group and two treated groups; seven eyes received 10 Gy, and eight eyes 20 Gy. The control group consisted of 10 eyes without treatment. All patients were followed at least four years, and the average follow-up duration was 6.56 years. The course of median visual acuity without treatment showed the similar result to that of MPS Group's report. In control group, visual acuity (VA) after four years was better in no eyes, unchanged in two eyes, and worse in eight eyes; in treated group, better in four eyes, unchanged in one eye, and worse in ten eyes. After four years VA was kept 20/200 or higher in 2 eyes without treatment, 4 eyes with 10 Gy, and 4 eyes with 20 Gy of radiation. Then maximum VA was 20/125 with no treatment, and 20/50 with radiation therapy. The natural course of the AMD of Japanese patients showed similar results to US patients. All eyes of AMD withort treatment got worse in VA, and some showed better outcome with radiation therapy; but it was not statistically significant. (author)

  16. Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Similarities to Age-Related Macular Degeneration and Potential Therapies.

    Science.gov (United States)

    Hulleman, John D

    2016-01-01

    Fibulin-3 (F3) is a secreted, disulfide-rich glycoprotein which is expressed in a variety of tissues within the body, including the retina. An Arg345Trp (R345W) mutation in F3 was identified as the cause of a rare retinal dystrophy, Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD). ML/DHRD shares many phenotypic similarities with age-related macular degeneration (AMD). The most prominent feature of ML/DHRD is the development of radial or honeycomb patterns of drusen which can develop as early as adolescence. Two independent mouse models of ML/DHRD show evidence of complement activation as well as retinal pigment epithelium (RPE) atrophy, strengthening the phenotypic connection with AMD. Because of its similarities with AMD, ML/DHRD is receiving increasing interest as a potential surrogate disease to study the underpinnings of AMD. This mini-review summarizes the current knowledge of F3 and points toward potential therapeutic strategies which directly or indirectly target cellular dysfunction associated with R345W F3. PMID:26427406

  17. Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-10-01

    The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

  18. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2015-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  19. Grading of Age-Related Macular Degeneration: Comparison between Color Fundus Photography, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Nils F. Mokwa

    2013-01-01

    Full Text Available Purpose. To compare color fundus photography (FP, fluorescein angiography (FA, and spectral domain optical coherence tomography (SDOCT for the detection of age-related macular degeneration (AMD, choroidal neovascularisation (CNV, and CNV activity. Methods. FPs, FAs, and SDOCT volume scans from 120 eyes of 66 AMD and control patients were randomly collected. Control eyes were required to show no AMD, but other retinal pathology was allowed. The presence of drusen, pigmentary changes, CNV, and signs for CNV activity was independently analyzed for all imaging modalities. Results. AMD was diagnosed based on FP in 75 eyes. SDOCT and FA showed sensitivity (specificity of 89% (76% and 92% (82%, respectively. CNV was present on FA in 68 eyes. Sensitivity (specificity was 78% (100% for FP and 94% (98% for SDOCT. CNV activity was detected by SDOCT or FA in 60 eyes with an agreement in 46 eyes. Sensitivity was 88% for SDOCT and 88% for FA. FP showed sensitivity of 38% and specificity of 98%. Conclusions. CNV lesions and activity may be missed by FP alone, but FP may help identifying drusen and pigmentary changes. SDOCT is highly sensitive for the detection of AMD, CNV, and CNV activity; however, it cannot fully replace FA.

  20. Metabolic risk factors, coping with stress, and psychological well-being in patients with age-related macular degeneration.

    Science.gov (United States)

    Cavar, Ivan; Lovrić, Sanjin; Vukojević, Mladenka; Sesar, Irena; Petric-Vicković, Ivanka; Sesar, Antonio

    2014-03-01

    The aim of this study was to determine the relationship between the risk factors (age, obesity, hypertension, hyperlipidemia, smoking, consumption of alchohol and drugs, positive family history, and exposure to sunlight), coping with stress, psychological well-being and age-related macular degeneration (ARMD). Forty patients with ARMD (case group) and 63 presbyopes (control group) participated in the study. Patient data were collected through general information questionnaire including patient habits, the COPE questionnaire that showed the way the patients handling stress, and the GHQ that analyzed the psychological aspects of their quality of life. These questionnaires were administered to the patients during ophthalmologic examination. The study involved 46 (44.66%) men and 57 (55.33%) women. Statistical analysis showed that the major risks for the development of ARMD were elevated cholesterol, triglycerides and LDL cholesterol in plasma. A significantly higher number ofARMD patients had a positive family history when compared with presbyopes. This study showed presbyopes to cope with emotional problems significantly better and to have a lower level of social dysfunction when compared with ARMD patients. However, it is necessary to conduct further studies in a large number of patients to determine more accurately the pathophysiological mechanisms of metabolic factors as well as the impact of the disease on the quality of life in patients with ARMD. PMID:24974669

  1. Pluripotent Stem Cell-Based Therapies in Combination with Substrate for the Treatment of Age-Related Macular Degeneration.

    Science.gov (United States)

    Pennington, Britney O; Clegg, Dennis O

    2016-06-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the western world, which severely decreases the quality of life in the patients and places an economic burden on their families and society. The disease is caused by the dysfunction of a specialized cell layer in the back of the eye called the retinal pigmented epithelium (RPE). Pluripotent stem cells can provide an unlimited source of RPE, and laboratories around the world are investigating their potential as therapies for AMD. To ensure the precise delivery of functional RPE to the diseased site, some groups are developing a therapy composed of mature RPE monolayers on a supportive scaffold for transplantation as an alternative to injecting a single-cell suspension. This review summarizes methods of generating RPE from pluripotent stem cells, compares biodegradable and biostable materials as scaffolds, and describes the specific combination of human embryonic stem cell-derived RPE on Parylene-C membranes, which is scheduled to begin clinical trials in the United Sates in 2016. Stem cell-derived RPE monolayers on scaffolds hold great promise for the treatment of AMD and other retinal diseases. PMID:26889704

  2. A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo.

    Science.gov (United States)

    Paun, Constantin C; Lechanteur, Yara T E; Groenewoud, Joannes M M; Altay, Lebriz; Schick, Tina; Daha, Mohamed R; Fauser, Sascha; Hoyng, Carel B; den Hollander, Anneke I; de Jong, Eiko K

    2016-01-01

    The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation in vitro. Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10(-13)) and complement activation levels in vivo (p = 8.31*10(-9)). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments. PMID:27241480

  3. [Review and expert opinion in age related macular degeneration. Focus on the pathophysiology, angiogenesis and pharmacological and clinical data].

    Science.gov (United States)

    Weber, M; Sennlaub, F; Souied, E; Cohen, S-Y; Béhar-Cohen, F; Milano, G; Tadayoni, R

    2014-09-01

    Age related macular degeneration (AMD) is a pathological aging of the macula, brought about by the interaction of genetic and environmental factors. It induces geographic atrophy of the retina and/or choroidal neovascularization. In the latter, abnormal vessels develop from the choriocapillaris, with the involvement of VEGF (vascular endothelial growth factor). The VEGF family includes several factors, including VEGF-A, B, C, D, F and PlGF (placental growth factor). Their biological properties and their affinities to the VEGFR1, VEGFR2 and VEGFR3 receptors found on endothelial cells differ. Exudative AMD involves mainly VEGF-A and VEGF-R2. Anti-VEGF agents used in ophthalmology (ranibizumab, bevacizumab and aflibercept) are designed to primarily target this pathway. In vitro, all have sufficient affinity to their ligands. Their therapeutic efficacy must therefore be judged based on clinical criteria. In clinical practice, the minimum number of injections required for a satisfactory result appears to be comparable with all the three. The few available studies on therapeutic substitutions of anti-VEGF compounds suggest that some patients may benefit from substituting the anti-VEGF in cases of an unsatisfactory response to an initial molecule. Although local side effects, including increased risk of geographic atrophy, and systemic effects, including vascular accidents, have been suggested, these risks remain low, specially compared to the benefits of the treatment. Differences in safety between anti-VEGF are theoretically possible but unproven. PMID:25190312

  4. Visual outcome of ranibizumab therapy for neovascular age related macular degeneration in the black population: a report of five cases

    Directory of Open Access Journals (Sweden)

    Roopa Vemala

    2010-08-01

    Full Text Available Roopa Vemala, Bhaskar Gupta, Sobha SivaprasadLaser and Retinal Research Unit, King’s College Hospital, London SE5 9RS, UKIntroduction: Neovascular age related macular degeneration (AMD is relatively uncommon in the black population. We report the 12-month outcome of ranibizumab therapy in five black patients with choroidal neovascular membrane (CNV secondary to AMD.Material and methods: Retrospective analysis of a prospective audit database maintained for all patients on ranibizumab therapy in a retinal specialist unit that caters to a multi-ethnic cohort in London, United Kingdom.Results: At 12 months, all the 5 patients maintained stable vision (loss of less than 15 ETDRS letters. However, none of them gained more than 15 ETDRS letters. All eyes showed early subretinal fibrosis while 2 patients showed extended areas of retinal pigment atrophy.Conclusion: Our case studies indicate that ranibizumab stabilizes the vision in black patients with CNV secondary to AMD but they tend to develop early subretinal fibrosis and retinal pigment atrophy.Keywords: choroidal neovascular membrane, Afro-Caribbean, blacks

  5. Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

  6. A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo

    Science.gov (United States)

    Paun, Constantin C.; Lechanteur, Yara T. E.; Groenewoud, Joannes M. M.; Altay, Lebriz; Schick, Tina; Daha, Mohamed R.; Fauser, Sascha; Hoyng, Carel B.; den Hollander, Anneke I.; de Jong, Eiko K.

    2016-01-01

    The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation in vitro. Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10−13) and complement activation levels in vivo (p = 8.31*10−9). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments. PMID:27241480

  7. Novel risk index for the identification of age-related macular degeneration using radon transform and DWT features.

    Science.gov (United States)

    Acharya, U Rajendra; Mookiah, Muthu Rama Krishnan; Koh, Joel E W; Tan, Jen Hong; Noronha, Kevin; Bhandary, Sulatha V; Rao, A Krishna; Hagiwara, Yuki; Chua, Chua Kuang; Laude, Augustinus

    2016-06-01

    Age-related Macular Degeneration (AMD) affects the central vision of aged people. It can be diagnosed due to the presence of drusen, Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in the fundus images. It is labor intensive and time-consuming for the ophthalmologists to screen these images. An automated digital fundus photography based screening system can overcome these drawbacks. Such a safe, non-contact and cost-effective platform can be used as a screening system for dry AMD. In this paper, we are proposing a novel algorithm using Radon Transform (RT), Discrete Wavelet Transform (DWT) coupled with Locality Sensitive Discriminant Analysis (LSDA) for automated diagnosis of AMD. First the image is subjected to RT followed by DWT. The extracted features are subjected to dimension reduction using LSDA and ranked using t-test. The performance of various supervised classifiers namely Decision Tree (DT), Support Vector Machine (SVM), Probabilistic Neural Network (PNN) and k-Nearest Neighbor (k-NN) are compared to automatically discriminate to normal and AMD classes using ranked LSDA components. The proposed approach is evaluated using private and public datasets such as ARIA and STARE. The highest classification accuracy of 99.49%, 96.89% and 100% are reported for private, ARIA and STARE datasets. Also, AMD index is devised using two LSDA components to distinguish two classes accurately. Hence, this proposed system can be extended for mass AMD screening. PMID:27107676

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

    Science.gov (United States)

    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. PMID:26827241

  9. Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration.

    Science.gov (United States)

    Ye, Fuxiang; Kaneko, Hiroki; Hayashi, Yumi; Takayama, Kei; Hwang, Shiang-Jyi; Nishizawa, Yuji; Kimoto, Reona; Nagasaka, Yosuke; Tsunekawa, Taichi; Matsuura, Toshiyuki; Yasukawa, Tsutomu; Kondo, Takaaki; Terasaki, Hiroko

    2016-05-01

    Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels. PMID:26923802

  10. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

    Science.gov (United States)

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

  11. Loosely coupled level sets for retinal layers and drusen segmentation in subjects with dry age-related macular degeneration

    Science.gov (United States)

    Novosel, Jelena; Wang, Ziyuan; de Jong, Henk; Vermeer, Koenraad A.; van Vliet, Lucas J.

    2016-03-01

    Optical coherence tomography (OCT) is used to produce high-resolution three-dimensional images of the retina, which permit the investigation of retinal irregularities. In dry age-related macular degeneration (AMD), a chronic eye disease that causes central vision loss, disruptions such as drusen and changes in retinal layer thicknesses occur which could be used as biomarkers for disease monitoring and diagnosis. Due to the topology disrupting pathology, existing segmentation methods often fail. Here, we present a solution for the segmentation of retinal layers in dry AMD subjects by extending our previously presented loosely coupled level sets framework which operates on attenuation coefficients. In eyes affected by AMD, Bruch's membrane becomes visible only below the drusen and our segmentation framework is adapted to delineate such a partially discernible interface. Furthermore, the initialization stage, which tentatively segments five interfaces, is modified to accommodate the appearance of drusen. This stage is based on Dijkstra's algorithm and combines prior knowledge on the shape of the interface, gradient and attenuation coefficient in the newly proposed cost function. This prior knowledge is incorporated by varying the weights for horizontal, diagonal and vertical edges. Finally, quantitative evaluation of the accuracy shows a good agreement between manual and automated segmentation.

  12. Incorporating prior knowledge to facilitate discoveries in a genome-wide association study on age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lee Wen-Chung

    2010-01-01

    Full Text Available Abstract Background Substantial genotyping data produced by current high-throughput technologies have brought opportunities and difficulties. With the number of single-nucleotide polymorphisms (SNPs going into millions comes the harsh challenge of multiple-testing adjustment. However, even with the false discovery rate (FDR control approach, a genome-wide association study (GWAS may still fall short of discovering any true positive gene, particularly when it has a relatively small sample size. Findings To counteract such a harsh multiple-testing penalty, in this report, we incorporate findings from previous linkage and association studies to re-analyze a GWAS on age-related macular degeneration. While previous Bonferroni correction and the traditional FDR approach detected only one significant SNP (rs380390, here we have been able to detect seven significant SNPs with an easy-to-implement prioritized subset analysis (PSA with the overall FDR controlled at 0.05. These include SNPs within three genes: CFH, CFHR4, and SGCD. Conclusions Based on the success of this example, we advocate using the simple method of PSA to facilitate discoveries in future GWASs.

  13. β-amyloidopathy in the Pathogenesis of Age-Related Macular Degeneration in Correlation with Neurodegenerative Diseases.

    Science.gov (United States)

    Ermilov, Victor V; Nesterova, Alla A

    2016-01-01

    Involvement of new biotechnology and genetic engineering methods to the study of the aging organism allowed to select a group of neurodegenerative diseases (NDD) which have a similar mechanism of pathogenesis including pathological processes of protein aggregation and its deposition in the structures of nerve tissue. The development of eye and brain from one embryonic germ layer, community of ethiopathogenetic and morphological manifestations of age-related macular degeneration (AMD) and Alzheimer's disease (AD), a common pathway of β-amyloid precursor protein (APP) are associated with the pathological aggregation of fibrillar β-amyloid (Aβ) protein and the development of β-amyloidopathy in structural elements of the eye and the brain. The review demonstrates the keynote of AMD and AD pathogenesis is β-amyloidopathy that is a manifestation of proteinopathy leading to cytotoxicity, neurodegeneration and the development of pathological apoptosis activated by the formation of intracellular Aβ. This view on the problem predetermines the development of new strategies for the creating of ophthalmogeriatric and neuroprotective drugs affecting the pathogenesis and including all stages of Aβ formation and pathological aggregation. PMID:26427402

  14. Genetic and functional dissection of ARMS2 in age-related macular degeneration and polypoidal choroidal vasculopathy.

    Directory of Open Access Journals (Sweden)

    Yong Cheng

    Full Text Available Age-related maculopathy susceptibility 2(ARMS2 was suggested to be associated with neovascular age-related macular degeneration (nAMD and polypoidal choroidal vasculopathy (PCV in multiple genetic studies in Caucasians and Japanese. To date, no biological properties have been attributed to the putative protein in nAMD and PCV. The complete genes of ARMS2 and HTRA1 including all exons and the promoter region were assessed using direct sequencing technology in 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients and 96 controls. Significant associations with both nAMD and PCV were observed in 2 polymorphisms of ARMS2 and HTRA1 rs11200638, with different genotypic distributions between nAMD and PCV (p<0.001. After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with nAMD and PCV (p<0.001. Then we overexpressed wild-type ARMS2 and ARMS2 A69S mutation (rs10490924 in RF/6A cells and RPE cells as in vitro study model. Cell proliferation, attachment, migration and tube formation were analyzed for the first time. Compare with wild-type ARMS2, A69S mutation resulted in a significant increase in proliferation and attachment but inhibited cell migration. Moreover, neither wild-type ARMS2 nor A69S mutation affected tube formation of RF/6A cells. There is a strong and consistent association of the ARMS2/HTRA1 locus with both nAMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Neither wild-type ARMS2 nor A69S mutation had direct association with neovascularisation in the pathogenesis of AMD.

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

    OpenAIRE

    Emily Y Chew; Clemons, Traci E.; SanGiovanni, John Paul; Danis, Ronald P; Ferris, Frederick L.; Elman, Michael J.; Antoszyk, Andrew; Ruby, Alan; Orth, David; Bressler, Susan B.; Fish, Gary; Hubbard, Baker; Klein, Michael; Chandra, Suresh; Blodi, Barbara

    2014-01-01

    The Age-Related Eye Disease Study (AREDS) formulation for treatment of age-related macular degeneration contains vitamins C, E, beta-carotene and zinc with copper. Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk of lung cancer from beta-carotene in smokers and former smokers. As previously reported in a secondary analysis, AREDS2 participants taking lutein/zeaxanthin with or without omega-3...

  16. The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration.

    Science.gov (United States)

    Stringham, J M; Hammond, B R; Nolan, J M; Wooten, B R; Mammen, A; Smollon, W; Snodderly, D M

    2008-11-01

    The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curves of lutein and zeaxanthin and the similarity of spatial density profiles to those measured in subjects without retinal disease. Macular pigment optical density (MPOD) spatial profiles were measured with an LED-based macular densitometer; spectral absorption curves were measured with a 3-channel Maxwellian view system including a monochromator. All patients were characterized via clinical exams and all but 2 subjects from whom data were obtained had masked grading of color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Most of the patients were in AREDS category 2 (27%) or 3 (57%). Patients with visual acuity as poor as 20/80 were included, and could perform the task as long as they could see the stimulus. Eighty-one percent of the patients screened were able to perform the cHFP task, and data were obtained from 30 AMD patients. Spatial profiles of MPOD were measured in 19 subjects who could see the stimulus at all tested loci. These profiles were highly similar to those that have been measured with HFP in subjects without retinal disease. The average shape of the spectral absorption curves for the AMD subjects corresponded well to an ex vivo template. These data support both the utility and validity of the cHFP method for measuring MPOD in subjects with intermediate stages of AMD. The ability to measure the retinal response to nutritional intervention is of practical importance for monitoring patients being supplemented with lutein and

  17. Segmentation error and macular thickness measurements obtained with spectral-domain optical coherence tomography devices in neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Moosang Kim

    2013-01-01

    Full Text Available Purpose: To evaluate frequency and severity of segmentation errors of two spectral-domain optical coherence tomography (SD-OCT devices and error effect on central macular thickness (CMT measurements. Materials and Methods: Twenty-seven eyes of 25 patients with neovascular age-related macular degeneration, examined using the Cirrus HD-OCT and Spectralis HRA + OCT, were retrospectively reviewed. Macular cube 512 × 128 and 5-line raster scans were performed with the Cirrus and 512 × 25 volume scans with the Spectralis. Frequency and severity of segmentation errors were compared between scans. Results: Segmentation error frequency was 47.4% (baseline, 40.7% (1 month, 40.7% (2 months, and 48.1% (6 months for the Cirrus, and 59.3%, 62.2%, 57.8%, and 63.7%, respectively, for the Spectralis, differing significantly between devices at all examinations (P < 0.05, except at baseline. Average error score was 1.21 ± 1.65 (baseline, 0.79 ± 1.18 (1 month, 0.74 ± 1.12 (2 months, and 0.96 ± 1.11 (6 months for the Cirrus, and 1.73 ± 1.50, 1.54 ± 1.35, 1.38 ± 1.40, and 1.49 ± 1.30, respectively, for the Spectralis, differing significantly at 1 month and 2 months (P < 0.02. Automated and manual CMT measurements by the Spectralis were larger than those by the Cirrus. Conclusions: The Cirrus HD-OCT had a lower frequency and severity of segmentation error than the Spectralis HRA + OCT. SD-OCT error should be considered when evaluating retinal thickness.

  18. Combined Transpupillary Thermotherapy with Subtenon Triamcinolone Injection in Treatment of Choroidal Neovascularization Secondary to Exudative Age Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    M Naseripour

    2008-04-01

    Full Text Available ABSTRACT: Introduction & Objective: In spite of several treatment methods which are being used to treat exudative age-related macular degeneration (ARMD like laser therapy, Intravitreal steroids injections or anti-vascular endothelial growth factors (VEGF, no method has been yet presented as the best treatment way. This study aimed to assess the effectiveness of combined transpupillary thermotherapy (TTT with subtenon triamcinolone acetonide (TA injection in treatment of choroidal neovascularization (CNV in patients with ARMD. Materials & Methods: In this clinical trial, 63 eyes of 57 patients with CNV secondary to exudative age-related macular degeneration (ARMD were studied. All CNVs (including 20 predominantly classic and 43 predominantly occult lesions were treated with diode laser (810nm. In 20 eyes with predominantly classic CNVs, 20 mg and 40 mg subtenon triamcinolone was injected in 12 and 8 eyes respectively. The patients were followed for a mean of 9.1 months (ranging from 5.5 to 16 months. The average number of treatment sessions was 1.25. In 43 eyes with occult CNV, 20 mg and 40 mg subtenon triamcinolone was injected in 31 eyes and in 12 eyes respectively. Mean follow up time was 12 months (4.5 to 23 months. Mean treatment times was 1.17. A variable spot size of 0.8, 1.2, 2 and 3 mm was used depending on the size of CNV and treatment was given in one area for 1 minute. Thermotherapy was adminstered through a contact lens at a power range between 120-560 mw. At the end of treatment, each patient randomly received 20 mg or 40 mg subtenon triamcinolone acetonide injection in superotemporal quadrant. Outcome was assessed with clinical and angiographic examination.collected data were analyzed by one-sample and paired –sample T test, using SPSS software. Results: At the end of the study in first group, visual acuity remained stable (0 to ± one line in 14 out of 20 (70 % of eyes, improved (> one line in 2 of 20 (10 % eyes and showed a

  19. An overview of multidisciplinary rehabilitation for age-related macular degeneration at the Henry Ford Center for Visual Rehabilitation and Research

    OpenAIRE

    Deol,

    2012-01-01

    Ramanpal K DeolHenry Ford Center for Visual Rehabilitation and Research, Livonia, MI, USAAbstract: Age-related macular degeneration (ARMD) is a leading cause of legal blindness in the United States. With the aging population increasing in numbers, there is a greater need for comprehensive low vision services. Visual impairment from ARMD can affect all aspects of living, from safety to well-being to participation in everyday and leisure activities. Low vision intervention is necessary for indi...

  20. Transconjunctival sutureless vitrectomy with tissue plasminogen activator, gas and intravitreal bevacizumab in the management of predominantly hemorrhagic age-related macular degeneration

    OpenAIRE

    Arias, Luis

    2010-01-01

    Luis Arias1,2, Jordi Monés11Institut de la Màcula i de la Retina, Centro Médico Teknon, Barcelona; 2Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, BarcelonaPurpose: To determine the efficacy and safety of treating predominantly hemorrhagic age-related macular degeneration (AMD) with transconjunctival sutureless vitrectomy (TSV), tissue plasminogen activator (tPA), sulphur hexafluoride (SF6), and intravitreal bevacizumab.Methods: Retro...

  1. Reliability and reproducibility of spectral and time domain optical coherence tomography images before and after correction for patients with age-related macular degeneration

    OpenAIRE

    Sadiq, Mohammad A.; Aymen Rashid; Roomasa Channa; Elham Hatef; Do, Diana V.; Quan Dong Nguyen; Sepah, Yasir J.

    2015-01-01

    Purpose: To evaluate the reproducibility and reliability of optical coherence tomography scans obtained using the time domain (TD-OCT) Stratus TM OCT, and the Spectral Domain (SD-OCT) Spectralis TM and Cirrus TM OCT devices before and after manual correction in eyes with either Neovascular (NV-AMD) or Non-Neovascular (NNV-AMD) age-related macular degeneration. Design: Prospective observational study. Methods: Setting: University-based retina practice. Patients: Thirty-six patients (50 eyes) w...

  2. Mitochondrial DNA Variants of Respiratory Complex I that Uniquely Characterize Haplogroup T2 Are Associated with Increased Risk of Age-Related Macular Degeneration

    OpenAIRE

    SanGiovanni, John Paul; Arking, Dan E.; Sudha K. Iyengar; Elashoff, Michael; Clemons, Traci E.; Reed, George F.; Henning, Alice K.; Sivakumaran, Theru A; Xu, Xuming; DeWan, Andrew; Agrón, Elvira; Rochtchina, Elena; Carolyn M Sue; Wang, Jie Jin; Mitchell, Paul

    2009-01-01

    Background Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been ...

  3. A Prospective Study of Treatment Patterns and 1-Year Outcome of Asian Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

    OpenAIRE

    Cheung, Chui Ming Gemmy; Xiang LI; Mathur, Ranjana; Lee, Shu Yen; Chan, Choi Mun; Yeo, Ian; Loh, Boon Kwang; Williams, Rachel; Wong, Edmund Yick-Mun; Wong, Doric; Wong, Tien Yin

    2014-01-01

    Objective To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV) and polypoidal choroidal vasculopathy (PCV). Design Prospective cohort, non-interventional study. Methods 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV...

  4. Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects

    OpenAIRE

    Park, Kyu Hyung; Ryu, Euijung; Tosakulwong, Nirubol; Wu, Yanhong; Edwards, Albert O.

    2009-01-01

    Purpose Common genetic variation in the complement component 1 inhibitor gene ( SERPING1 ) was recently reported to increase the risk of developing age-related macular degeneration (AMD). This study was performed to replicate the association between SERPING1 and AMD. Methods Seven single nucleotide polymorphisms (SNPs) tagging common haplotypes across SERPING1 were genotyped on 786 (The Mayo Clinic) subjects and the association with AMD studied using single SNP and haplotype association analy...

  5. Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study

    OpenAIRE

    Osthoff, Michael; Dean, Melinda M.; Baird, Paul N.; Richardson, Andrea J.; Daniell, Mark; Guymer, Robyn H.; Eisen, Damon P

    2015-01-01

    Background In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and s...

  6. Age-related macular degeneration: Prevalence and risk factors - a cross-sectional study : The Tromsø Study 2007/2008

    OpenAIRE

    Erke, Maja Gran

    2013-01-01

    Age-related macular degeneration (AMD) is an important cause of visual impairment and blindness worldwide. The number of people affected by the disease is expected to rise due to increasing longevity. Development of adequate eye care for these patients should be based on knowledge about the prevalence of AMD. Further, preventive measures are the best strategy for any disease. The aims of this thesis were to estimate the prevalence of AMD and examine risk factors associated with AMD. ...

  7. Visual acuity and contrast sensitivity outcomes in Indian eyes undergoing photodynamic therapy with intravitreal injection of triamcinolone acetonide in age-related macular degeneration

    OpenAIRE

    Kumar Atul; Sinha Subijay; Kumar Vikram

    2007-01-01

    Purpose: To evaluate photodynamic therapy (PDT) with verteporfin along with intravitreal triamcinolone acetonide (IVTA) in the treatment of neovascular age-related macular degeneration (AMD). Materials and Methods: This prospective interventional case series included 23 patients (23 eyes) of choroidal neovascularization due to neovascular AMD who were treated with PDT with verteporfin followed by an injection of 4 mg IVTA. The main outcome measures were visual acuity (VA), contrast sensiti...

  8. Dietary n-3 Fatty Acid, α-Tocopherol, Zinc, vitamin D, vitamin C, and β-carotene are Associated with Age-Related Macular Degeneration in Japan

    OpenAIRE

    Aya Aoki; Maiko Inoue; Elizabeth Nguyen; Ryo Obata; Kazuaki Kadonosono; Shoji Shinkai; Hideki Hashimoto; Satoshi Sasaki; Yasuo Yanagi

    2016-01-01

    This case-control study reports the association between nutrient intake and neovascular age-related macular degeneration (AMD) in Japan. The nutrient intake of 161 neovascular AMD cases from two university hospitals and 369 population-based control subjects from a cohort study was assessed using a brief-type self-administered questionnaire on diet history, which required respondent recall of the usual intake of 58 foods during the preceding month. Energy-adjusted nutrient intake values were c...

  9. Vasodilators and Blood Pressure Lowering Medications and Age-Related Macular Degeneration: The Beaver Dam Eye Study

    Science.gov (United States)

    Klein, Ronald; Myers, Chelsea E.; Klein, Barbara E. K.

    2014-01-01

    Objective To examine the association of vasodilator and antihypertensive medication use to the incidence of age-related macular degeneration (AMD). Design A longitudinal population-based study. Participants Persons 43–86 years of age living in Beaver Dam, Wisconsin in 1988–1990. Methods Examinations were performed every 5 years over a 20-year period. There were 9676 total person-visits over the course of the study. Status of AMD was determined from grading retinal photographs. Main Outcome Measures Incidence of AMD. Results The 5-year incidence of early AMD over the 20-year period was 8.4%, for late AMD it was 1.4%, for pure geographic atrophy (GA) it was 0.6%, for exudative AMD it was 0.9%, and for progression of AMD it was 24.9%. While adjusting for age, sex, and other factors, using a vasodilator (hazard ratio [HR]=1.72; 95% confidence interval [CI] 1.25 – 2.38), particularly oral nitroglycerin (1.81, 1.14 – 2.90) was associated with an increased risk of early AMD. Using an oral beta blocker was associated with an increased hazard of incident exudative AMD (1.71, 1.04 – 2.82) but not pure GA (0.51, 0.20 – 1.29) or progression (0.92, 0.67 – 1.28) of AMD over the 20-year period. Conclusions Use of vasodilators is associated with a 72% increase in the hazard of incidence of early AMD and use of oral beta blockers is associated with a 71% increase in the hazard of incident exudative AMD. If these findings are replicated it may have implications for care of older adults as vasodilators and oral beta blockers are commonly used drugs by older persons. PMID:24793737

  10. Assessment of targeting accuracy of a low-energy stereotactic radiosurgery treatment for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Taddei, Phillip J; Newhauser, Wayne D [Radiation Physics Department, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); Chell, Erik; Hansen, Steven; Gertner, Michael, E-mail: ptaddei@mdanderson.or [Oraya Therapeutics, Inc., 8000 Jarvis Avenue, Newark, CA 94560 (United States)

    2010-12-07

    Age-related macular degeneration (AMD), a leading cause of blindness in the United States, is a neovascular disease that may be controlled with radiation therapy. Early patient outcomes of external beam radiotherapy, however, have been mixed. Recently, a novel multimodality treatment was developed, comprising external beam radiotherapy and concomitant treatment with a vascular endothelial growth factor inhibitor. The radiotherapy arm is performed by stereotactic radiosurgery, delivering a 16 Gy dose in the macula (clinical target volume, CTV) using three external low-energy x-ray fields while adequately sparing normal tissues. The purpose of our study was to test the sensitivity of the delivery of the prescribed dose in the CTV using this technique and of the adequate sparing of normal tissues to all plausible variations in the position and gaze angle of the eye. Using Monte Carlo simulations of a 16 Gy treatment, we varied the gaze angle by {+-}5{sup 0} in the polar and azimuthal directions, the linear displacement of the eye {+-}1 mm in all orthogonal directions, and observed the union of the three fields on the posterior wall of spheres concentric with the eye that had diameters between 20 and 28 mm. In all cases, the dose in the CTV fluctuated <6%, the maximum dose in the sclera was <20 Gy, the dose in the optic disc, optic nerve, lens and cornea were <0.7 Gy and the three-field junction was adequately preserved. The results of this study provide strong evidence that for plausible variations in the position of the eye during treatment, either by the setup error or intrafraction motion, the prescribed dose will be delivered to the CTV and the dose in structures at risk will be kept far below tolerance doses.

  11. Analysis of rare variants in the C3 gene in patients with age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Maheswara R Duvvari

    Full Text Available Age-related macular degeneration (AMD is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3 gene have been associated with AMD and recently a rare C3 variant (Lys155Gln was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS, we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P=0.04, Arg735Trp (OR=17.4, 95% CI=2.2-136; P=0.0003, and Ser1619Arg (OR=5.2, 95% CI=1.0-25; P=0.05 at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant.

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

    Directory of Open Access Journals (Sweden)

    Keane PA

    2015-02-01

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

  13. Expression analysis of an evolutionarily conserved alternative splicing factor, Sfrs10, in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Devi Krishna Priya Karunakaran

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness in the elderly population. Hypoxic stress created in the micro-environment of the photoreceptors is thought to be the underlying cause that results in the pathophysiology of AMD. However, association of AMD with alternative splicing mediated gene regulation is not well explored. Alternative Splicing is one of the primary mechanisms in humans by which fewer protein coding genes are able to generate a vast proteome. Here, we investigated the expression of a known stress response gene and an alternative splicing factor called Serine-Arginine rich splicing factor 10 (Sfrs10. Sfrs10 is a member of the serine-arginine (SR rich protein family and is 100% identical at the amino acid level in most mammals. Immunoblot analysis on retinal extracts from mouse, rat, and chicken showed a single immunoreactive band. Further, immunohistochemistry on adult mouse, rat and chicken retinae showed pan-retinal expression. However, SFRS10 was not detected in normal human retina but was observed as distinct nuclear speckles in AMD retinae. This is in agreement with previous reports that show Sfrs10 to be a stress response gene, which is upregulated under hypoxia. The difference in the expression of Sfrs10 between humans and lower mammals and the upregulation of SFRS10 in AMD is further reflected in the divergence of the promoter sequence between these species. Finally, SFRS10+ speckles were independent of the SC35+ SR protein speckles or the HSF1+ stress granules. In all, our data suggests that SFRS10 is upregulated and forms distinct stress-induced speckles and might be involved in AS of stress response genes in AMD.

  14. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration.

    Science.gov (United States)

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L; Kamei, Motohiro

    2012-05-15

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  15. A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Siobhan M Cashman

    Full Text Available Age related macular degeneration (AMD is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV. Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD.

  16. Intravitreal Expansile Gas and Bevacizumab Injection for Submacular Hemorrhage Due to Neovascular Age-related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Ramin Nourinia

    2010-01-01

    Full Text Available Purpose: To evaluate the results of intravitreal expansile gas injection, with or without recombinant tissue plasminogen activator (rtPA, followed by intravitreal bevacizumab injection for treatment of submacular hemorrhage (SMH secondary to neovascular age-related macular degeneration (AMD. Methods: In this interventional case series, 5 eyes of 5 patients with SMH secondary to choroidal neovascularization (CNV due to neovascular AMD were treated with 0.3 cc intravitreal SF6 (and 50 μg of rtPA in two eyes, followed by face-down positioning; 24 hours later, 1.25 mg of bevacizumab was injected intravitreally. Main outcome measures included displacement of SMH and best corrected visual acuity (BCVA. Results: Mean patient age was 75.6±9.2 (range, 60-83 years, mean duration of symptoms was 6.4±3.2 (range, 3-10 days, and mean number of bevacizumab injections was 1.8 (range, 1-3. Mean preoperative BCVA was 1.28±0.27 logMAR which improved significantly to 0.57±0.33 logMAR at 12 months (P=0.042. SMH displacement occurred in all eyes, and visual acuity improved and remained stable during the follow-up period of 12 months. Conclusion: Intravitreal expansile gas injection, with or without rtPA, followed by intravitreal bevacizumab injection, seems to be an effective modality for SMH displacement and treatment of the underlying CNV in neovascular AMD.

  17. Systemic adverse events after intravitreal bevacizumab versus ranibizumab for age-related macular degeneration: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available OBJECTIVE: To assess whether the incidence of systemic adverse events differs between those who used bevacizumab and those who used ranibizumab in the treatment of age-related macular degeneration (AMD. METHODS: A systematic literature search was conducted to identify randomised controlled trials (RCTs comparing the use of intravitreal bevacizumab with the use of ranibizumab in AMD patients. Results were expressed as risk ratios (RRs with accompanying 95% confidence intervals (CIs. The data were pooled using the fixed-effect or random-effect model according to the heterogeneity present. RESULTS: Four RCTs were included in the final meta-analysis. Overall, the quality of the evidence was high. There were 2,613 treated patients: 1,291 treated with bevacizumab and 1,322 treated with ranibicizumab. No significant differences between bevacizumab use and ranizumab use were found in terms of the incidence of death from all causes, arteriothrombotic events, stroke, nonfatal myocardial infarction, vascular death, venous thrombotic events, and hypertension, with the pooled RRs being 1.11 (0.77, 1.61, 1.03 (0.69,1.55, 0.84 (0.39,1.80, 0.97 (0.48, 1.96, 1.24 (0.63, 2.44, 2.38 (0.94, 6.04, and 1.02 (0.29, 3.62, respectively. CONCLUSIONS: The meta-analysis shows that both treatments are comparably safe. However, the findings from our study must be confirmed in future research via well-designed cohort or intervention studies because of the limited number of studies.

  18. Assessment of targeting accuracy of a low-energy stereotactic radiosurgery treatment for age-related macular degeneration

    International Nuclear Information System (INIS)

    Age-related macular degeneration (AMD), a leading cause of blindness in the United States, is a neovascular disease that may be controlled with radiation therapy. Early patient outcomes of external beam radiotherapy, however, have been mixed. Recently, a novel multimodality treatment was developed, comprising external beam radiotherapy and concomitant treatment with a vascular endothelial growth factor inhibitor. The radiotherapy arm is performed by stereotactic radiosurgery, delivering a 16 Gy dose in the macula (clinical target volume, CTV) using three external low-energy x-ray fields while adequately sparing normal tissues. The purpose of our study was to test the sensitivity of the delivery of the prescribed dose in the CTV using this technique and of the adequate sparing of normal tissues to all plausible variations in the position and gaze angle of the eye. Using Monte Carlo simulations of a 16 Gy treatment, we varied the gaze angle by ±50 in the polar and azimuthal directions, the linear displacement of the eye ±1 mm in all orthogonal directions, and observed the union of the three fields on the posterior wall of spheres concentric with the eye that had diameters between 20 and 28 mm. In all cases, the dose in the CTV fluctuated <6%, the maximum dose in the sclera was <20 Gy, the dose in the optic disc, optic nerve, lens and cornea were <0.7 Gy and the three-field junction was adequately preserved. The results of this study provide strong evidence that for plausible variations in the position of the eye during treatment, either by the setup error or intrafraction motion, the prescribed dose will be delivered to the CTV and the dose in structures at risk will be kept far below tolerance doses.

  19. Low-dose fractionated percutaneous teletherapy in age-related macular degeneration with subfoveolar neovascularization - 3 year results

    International Nuclear Information System (INIS)

    The effect of low dose fractionated percutaneous teletherapy to visual acuity and the changes in subfoveolar neovascular membranes in age-related macular degeneration were investigated. Patients and Method: 126 eyes of 118 patients (age 55-89 years; mean 74 ys.) were treated. Best distal and near visual acuity was assessed prior to (= initial visual acuity [IVA]) and 3, 6, 12, 18, 24, and 36 months after teletherapy. Fluorescein angiography was performed prior to and 6, 12, 24 and 36 months after radiation therapy. For analysis patients were divided into different groups by IVA and membrane size. Maximal duration of observation was 36 months. Teletherapy was done by a 9-MeV photon linear accelerator through a lateral port in half-beam technique with a single dose of 2 Gy up to a total dose of 20 Gy within 12 days. Results: No severe negative side effects have been observed. Eight patients reported of epiphora and four patients complained of transient sicca syndrome. Visual acuity decreased more than one line in the group IVA 0.05-0.2. The group IVA 0.3-0.5 remained unchanged for 1 year. We found a tendency for increased visual acuity in group IVA ≥ 0.6 for 18 months. After that time both groups showed decreased visual acuity, but all these patients reported of reduced metamorphopsia and increased color and contrast perception. Conclusions: There is an influence of low dose fractionated percutaneous teletherapy on visual acuity, subfoveal neovascular membranes and metamorphopsia. IVA and duration of anamnesis play an important role. There seems to be no persistent effect; possibly increased dosage will bring a benefit. (orig.)

  20. Assessment of targeting accuracy of a low-energy stereotactic radiosurgery treatment for age-related macular degeneration

    Science.gov (United States)

    Taddei, Phillip J.; Chell, Erik; Hansen, Steven; Gertner, Michael; Newhauser, Wayne D.

    2010-12-01

    Age-related macular degeneration (AMD), a leading cause of blindness in the United States, is a neovascular disease that may be controlled with radiation therapy. Early patient outcomes of external beam radiotherapy, however, have been mixed. Recently, a novel multimodality treatment was developed, comprising external beam radiotherapy and concomitant treatment with a vascular endothelial growth factor inhibitor. The radiotherapy arm is performed by stereotactic radiosurgery, delivering a 16 Gy dose in the macula (clinical target volume, CTV) using three external low-energy x-ray fields while adequately sparing normal tissues. The purpose of our study was to test the sensitivity of the delivery of the prescribed dose in the CTV using this technique and of the adequate sparing of normal tissues to all plausible variations in the position and gaze angle of the eye. Using Monte Carlo simulations of a 16 Gy treatment, we varied the gaze angle by ±5° in the polar and azimuthal directions, the linear displacement of the eye ±1 mm in all orthogonal directions, and observed the union of the three fields on the posterior wall of spheres concentric with the eye that had diameters between 20 and 28 mm. In all cases, the dose in the CTV fluctuated <6%, the maximum dose in the sclera was <20 Gy, the dose in the optic disc, optic nerve, lens and cornea were <0.7 Gy and the three-field junction was adequately preserved. The results of this study provide strong evidence that for plausible variations in the position of the eye during treatment, either by the setup error or intrafraction motion, the prescribed dose will be delivered to the CTV and the dose in structures at risk will be kept far below tolerance doses.

  1. Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration

    Science.gov (United States)

    Michalska-Małecka, Katarzyna; Kabiesz, Adam; Kimsa, Malgorzata W; Strzałka-Mrozik, Barbara; Formińska-Kapuścik, Maria; Nita, Malgorzata; Mazurek, Urszula

    2016-01-01

    The purpose of this study was to evaluate the systemic effects of intravitreal ranibizumab (Lucentis) treatment in patients with neovascular age-related macular degeneration (AMD). The impact of intravitreal ranibizumab injections on central retinal thickness (CRT) of treated and contralateral untreated eyes, and differences in gene expression patterns in the peripheral blood mononuclear cells were analyzed. The study included 29 patients aged 50 years old and over with diagnosed neovascular AMD. The treatment was defined as 0.5 mg of ranibizumab injected intravitreally in the form of one injection every month during the period of 3 months. CRT was measured by optical coherence tomography. The gene expression profile was assigned using oligonucleotide microarrays of Affymetrix HG-U133A. Studies have shown that there was a change of CRT between treated and untreated eyes, and there were differences in CRT at baseline and after 1, 2, and 3 months of ranibizumab treatment. Three months after intravitreal injection, mean CRT was reduced in the treated eyes from 331.97±123.62 to 254.31±58.75 μm, while mean CRT in the untreated fellow eyes reduced from 251.07±40.29 to 235.45±36.21 μm at the same time. Furthermore, the research has shown that among all transcripts, 3,097 expresses change after the ranibizumab treatment in relation to controls. Among these transcripts, 1,339 were up-regulated, whereas 1,758 were down-regulated. Our results show the potential systemic effects of anti-VEGF therapy for AMD. Moreover, our study indicated different gene expression in peripheral blood mononuclear cells before and after intravitreal ranibizumab treatment. PMID:27069359

  2. Topical application of PPADS inhibits complement activation and choroidal neovascularization in a model of age-related macular degeneration.

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    Kerstin Birke

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC in their choroidal blood vessels and retinal pigment epithelium (RPE. MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF that promotes the formation of choroidal neovascularization (CNV. High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as α-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS as a potential treatment for AMD. We found that 4.17 µM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 µM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia.

  3. Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.

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    Tina Ristau

    Full Text Available Age-related macular degeneration (AMD is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs in or near 23 AMD associated risk genes. Component 3 (C3 and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH genes and complement factor B (CFB genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002, higher age (p = 1.56 × 10(-7, AMD phenotype (p = 1.15 × 10(-11 and the two SNPs in the C3 gene rs6795735 (p = 0.04 and rs2230199 (p = 0.04. Lower C3d/C3 ratios were found for diabetes (p = 2.87 × 10(-6, higher body mass index (p = 1.00 × 10(-13, the SNPs rs1410996 (p = 0.0001, rs800292 (p = 0.003, rs12144939 (p = 4.60 × 10(-6 in CFH, rs4151667 (p = 1.01 × 10(-5 in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.

  4. Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12

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    Weeks Daniel E

    2004-07-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is a complex disorder that is responsible for the majority of central vision loss in older adults living in developed countries. Phenotypic and genetic heterogeneity complicate the analysis of genome-wide scans for AMD susceptibility loci. The ordered subset analysis (OSA method is an approach for reducing heterogeneity, increasing statistical power for detecting linkage, and helping to define the most informative data set for follow-up analysis. OSA assesses the linkage evidence in subsets of potentially more homogeneous families by rank-ordering family-specific lod scores with respect to trait-associated covariates or phenotypic features. Here, we present results of incorporating five continuous covariates into our genome-wide linkage analysis of 389 microsatellite markers in 62 multiplex families: Body mass index (BMI, systolic (SBP and diastolic (DBP blood pressure, intraocular pressure (IOP, and pack-years of cigarette smoking. Chromosome-wide significance of increases in nonparametric multipoint lod scores in covariate-defined subsets relative to the overall sample was assessed by permutation. Results Using a correction for testing multiple covariates, statistically significant lod score increases were observed for two chromosomal regions: 14q13 with a lod score of 3.2 in 28 families with average IOP ≤ 15.5 (p = 0.002, and 6q14 with a lod score of 1.6 in eight families with average BMI ≥ 30.1 (p = 0.0004. On chromosome 16p12, nominally significant lod score increases (p ≤ 0.05, up to a lod score of 2.9 in 32 families, were observed with several covariate orderings. While less significant, this was the only region where linkage evidence was associated with multiple clinically meaningful covariates and the only nominally significant finding when analysis was restricted to advanced forms of AMD. Families with linkage to 16p12 had higher averages of SBP, IOP and BMI and were

  5. Computational assessment of effective dose and patient specific doses for kilovoltage stereotactic radiosurgery of wet age-related macular degeneration

    Science.gov (United States)

    Hanlon, Justin Mitchell

    Age-related macular degeneration (AMD) is a leading cause of vision loss and a major health problem for people over the age of 50 in industrialized nations. The current standard of care, ranibizumab, is used to help slow and in some cases stabilize the process of AMD, but requires frequent invasive injections into the eye. Interest continues for stereotactic radiosurgery (SRS), an option that provides a non-invasive treatment for the wet form of AMD, through the development of the IRay(TM) (Oraya Therapeutics, Inc., Newark, CA). The goal of this modality is to destroy choroidal neovascularization beneath the pigment epithelium via delivery of three 100 kVp photon beams entering through the sclera and overlapping on the macula delivering up to 24 Gy of therapeutic dose over a span of approximately 5 minutes. The divergent x-ray beams targeting the fovea are robotically positioned and the eye is gently immobilized by a suction-enabled contact lens. Device development requires assessment of patient effective dose, reference patient mean absorbed doses to radiosensitive tissues, and patient specific doses to the lens and optic nerve. A series of head phantoms, including both reference and patient specific, was derived from CT data and employed in conjunction with the MCNPX 2.5.0 radiation transport code to simulate treatment and evaluate absorbed doses to potential tissues-at-risk. The reference phantoms were used to evaluate effective dose and mean absorbed doses to several radiosensitive tissues. The optic nerve was modeled with changeable positions based on individual patient variability seen in a review of head CT scans gathered. Patient specific phantoms were used to determine the effect of varying anatomy and gaze. The results showed that absorbed doses to the non-targeted tissues were below the threshold levels for serious complications; specifically the development of radiogenic cataracts and radiation induced optic neuropathy (RON). The effective dose

  6. Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study

    Directory of Open Access Journals (Sweden)

    Kenney M Cristina

    2013-01-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924 and CFH (T > C; Try402His, rs1061170. Methods Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. Results The JTU haplogroup cluster occurred in 34% (55/162 of AMD subjects versus 15% (24/164 of normal (OR = 2.99; p = 0.0001. This association was slightly greater in males (OR = 3.98, p = 0.005 than the female population (OR = 3.02, p = 0.001. Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001 and CFH (rs1061170; p = 0.027 SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924 or CFH (rs1061170 SNPs on the JTU haplogroup background. Conclusions There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924 and CFH (rs1061170 genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.

  7. Refractive error and risk of early or late age-related macular degeneration: a systematic review and meta-analysis.

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    Ying Li

    Full Text Available OBJECTIVE: To summarize relevant evidence investigating the associations between refractive error and age-related macular degeneration (AMD. DESIGN: Systematic review and meta-analysis. METHODS: We searched Medline, Web of Science, and Cochrane databases as well as the reference lists of retrieved articles to identify studies that met the inclusion criteria. Extracted data were combined using a random-effects meta-analysis. Studies that were pertinent to our topic but did not meet the criteria for quantitative analysis were reported in a systematic review instead. MAIN OUTCOME MEASURES: Pooled odds ratios (ORs and 95% confidence intervals (CIs for the associations between refractive error (hyperopia, myopia, per-diopter increase in spherical equivalent [SE] toward hyperopia, per-millimeter increase in axial length [AL] and AMD (early and late, prevalent and incident. RESULTS: Fourteen studies comprising over 5800 patients were eligible. Significant associations were found between hyperopia, myopia, per-diopter increase in SE, per-millimeter increase in AL, and prevalent early AMD. The pooled ORs and 95% CIs were 1.13 (1.06-1.20, 0.75 (0.56-0.94, 1.10 (1.07-1.14, and 0.79 (0.73-0.85, respectively. The per-diopter increase in SE was also significantly associated with early AMD incidence (OR, 1.06; 95% CI, 1.02-1.10. However, no significant association was found between hyperopia or myopia and early AMD incidence. Furthermore, neither prevalent nor incident late AMD was associated with refractive error. Considerable heterogeneity was found among studies investigating the association between myopia and prevalent early AMD (P = 0.001, I2 = 72.2%. Geographic location might play a role; the heterogeneity became non-significant after stratifying these studies into Asian and non-Asian subgroups. CONCLUSION: Refractive error is associated with early AMD but not with late AMD. More large-scale longitudinal studies are needed to further investigate

  8. Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study

    Science.gov (United States)

    Borrelli, Emma; Diadori, Angelica; Zalaffi, Alessandro; Bocci, Velio

    2012-01-01

    AIM To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haematochemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (Pozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, Pozonated autohaemotherapy may exert a role in reducing oxidative stress by endogenously stimulating the production of antioxidant molecules. CONCLUSION The results of this study suggests that major ozonated autohaemotherapy could be a safe and effective therapeutic option for high-risk patients

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

    Science.gov (United States)

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

    2016-01-01

    Purpose To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD). Design Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters. Patients Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV) secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA) score between 20 and 78 letters on an EDTRS like chart in the study eye. Methods Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed. Main Outcome Measures Primary outcome was the change in BCVA in the study eye from baseline to 12 months. Results The mean gain in BCVA was 5.1 (±14.1) letters in the bevacizumab group (n = 161) and 6.4 (±12.2) letters in the ranibizumab group (n = 166) (p = 0.37). The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038). No significant differences in absolute CRT and CRT change (p = 0.13) or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively) were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal) differed significantly (p = 0.020), with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively). Conclusions Bevacizumab was not inferior to ranibizumab. The

  10. Investigation of a 90Sr/90Y source for intra-ocular treatment of wet age-related macular degeneration

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to perform an extensive investigation of an approximately 2.5 mm long 90Sr/90Y source designed for treating wet age-related macular degeneration. Methods: As part of this investigation, a NIST-traceable absorbed dose to water calibration technique was established, and a source deployment verification test was developed. The influence of treatment cannula construction tolerance on the measurements as well as the dose delivered to the patient was investigated using the Monte Carlo code MCNP5. Variation between production cannulae was quantified experimentally using a well-type ionization chamber, and additional measurements along with Monte Carlo calculations of the collimating insert used for source deployment verification were performed to validate the model. Results: Maximum variation in the integrated target dose was seen when the source was shifted laterally within the treatment cannula. For the well chamber measurements, the observed standard deviation in ionization current for a single source placed in different reference cannulae was ±0.3%, with a maximum observed range of less than ±0.5%. Clinical cannulae in the collimating insert showed an average of 17.8%±0.4% of the reference signal when sources were fully deployed compared to 18.5% predicted by Monte Carlo calculations. This discrepancy has been attributed primarily to construction of the collimator since the collimation gap was observed to be approximately 0.025-0.075 mm smaller than specified. Construction tolerance of the well chamber insert as well as position tolerance of the cannula tip were both investigated, and their influence on the predicted signal was quantified. Additional measurements along with Monte Carlo based calculations of the collimating insert with polyethylene spacers added to the setup were performed to validate the Monte Carlo model. The shimmed Monte Carlo and measured data agree to within 1%, which is a magnitude difference of

  11. The effect of terahertz electromagnetic radiation on cardiovascular system and orbital vessels in age-related macular degeneration

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    K. U. Eremenko

    2014-07-01

    Full Text Available Aim.To study the effect of terahertz (THz radiation at atmospheric oxygen frequency (129 GHz on cardiovascular and hemodynamic parameters of orbital arteries following the irradiation of bioactive points in healthy volunteers and age-related macular degeneration (AMD patients.Materials and methods. 18 healthy volunteers (36 eyes and 20 AMD patients (34 eyes were examined. Blood pressure (BP, heart rate (HR, systolic and diastolic blood flow velocities, resistance index (RI in orbital arteries before and following THz radiation of two bioactive points VB1 and TR23 at atmospheric oxygen frequency 129 GHz in continuouswave generation mode were measured.Results. First data on the effect of THz waves at atmospheric oxygen irradiation and absorption molecular spectrum frequency (129 GHz in continuous wave generation mode on ocular hemodynamics in healthy persons and AMD patients are presented. Following THz irradiation at atmospheric oxygen frequency (129 GHz, common hemodynamicparameters (BP, HR decreased. In healthy volunteers, systolic and diastolic BP reduced by 22.83±4.09 and 8.82±0.98 mm Hg, respectively (р<0.05, HR reduced by 6.11±0.15 bpm (р<0.05. In AMD patients, systolic and diastolic BP significantly decreased by 45.55±0.43 and 9.56±1.42 mm Hg, respectively (р<0.05, HR decreased by 6.15±1.1 bpm (р<0.05. In AMD patients, systolic blood flow velocity significantly reduced by 2.89±0.1 cm / sec in central retinal artery and increased by0.9‑5.97 cm / sec in short posterior ciliary arteries and ophthalmic artery. RI in these vessels decreased by 0.13, 0.11, 0.13 and 0.12, respectively.Conclusion. THz waves at atmospheric oxygen irradiation and absorption molecular spectrum frequency (129 GHz are safe and cause no side effects on general health of healthy volunteers and AMD patients. Besides, this method improves ocular hemodynamics.

  12. Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration

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    Hageman Gregory S

    2011-07-01

    Full Text Available Abstract Predictive tests for estimating the risk of developing late-stage neovascular age-related macular degeneration (AMD are subject to unique challenges. AMD prevalence increases with age, clinical phenotypes are heterogeneous and control collections are prone to high false-negative rates, as many control subjects are likely to develop disease with advancing age. Risk prediction tests have been presented previously, using up to ten genetic markers and a range of self-reported non-genetic variables such as body mass index (BMI and smoking history. In order to maximise the accuracy of prediction for mainstream genetic testing, we sought to derive a test comparable in performance to earlier testing models but based purely on genetic markers, which are static through life and not subject to misreporting. We report a multicentre assessment of a larger panel of single nucleotide polymorphisms (SNPs than previously analysed, to improve further the classification performance of a predictive test to estimate the risk of developing choroidal neovascular (CNV disease. We developed a predictive model based solely on genetic markers and avoided inclusion of self-reported variables (eg smoking history or non-static factors (BMI, education status that might otherwise introduce inaccuracies in calculating individual risk estimates. We describe the performance of a test panel comprising 13 SNPs genotyped across a consolidated collection of four patient cohorts obtained from academic centres deemed appropriate for pooling. We report on predictive effect sizes and their classification performance. By incorporating multiple cohorts of homogeneous ethnic origin, we obtained >80 per cent power to detect differences in genetic variants observed between cases and controls. We focused our study on CNV, a subtype of advanced AMD associated with a severe and potentially treatable form of the disease. Lastly, we followed a two-stage strategy involving both test model

  13. Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration: A Meta-Analysis

    OpenAIRE

    Zhou, Qiang; Shaffer, James; Ying, Gui-shuang

    2016-01-01

    Importance The fellow eye of patients with unilateral neovascular age-related degeneration (nAMD) is at increased risk of developing late AMD. Several cohort studies have evaluated the prevalence of pseudodrusen and the association between pseudodrusen and late AMD in the fellow eye of patients with unilateral nAMD. However, these studies have limited sample sizes and their results are inconsistent. Objective To evaluate the prevalence rate of pseudodrusen, and the association between pseudod...

  14. Chinese Medicine for Eye Diseases: Principles of Treatment of Age Related Macular Degeneration-AMD%Chinese Medicine for Eye Diseases:Principles of Treatment of Age Related Macular Degeneration-AMD

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The AMD causes a deterioration of the central field of vision of the human eye caused by loss of function of the macula. The macula is the central part of the retina, the part that receives the most freely detailed information since it contains a considerable number of daylight sensitive and colour sensitive photoreceptor cells. People with little skin pigments like European people are more frequently affected than people from the Asian continent for example. Three quarters of the people who are affected by AMD suffer from the dry form of macular degeneration which means lack of fluid or dehydration of the back part of the eye. There is no effective treatment to be known so far.

  15. Radiotherapy of macular lesions in age-related macular degeneration (A.M.D.): preliminary results of a clinical study conducted in Lyon, France

    International Nuclear Information System (INIS)

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

  16. R102G polymorphism of the C3 gene associated with exudative age-related macular degeneration in a French population

    OpenAIRE

    Zerbib, Jennyfer; Richard, Florence; Puche, Nathalie; Leveziel, Nicolas; Cohen, Salomon Y.; Korobelnik, Jean-François; Sahel, José; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel; Souied, Eric H

    2010-01-01

    Purpose Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, underlying the role of the complement pathway in AMD. Our purpose was to analyze the role of the R102G polymorphism of the complement component (C3) gene in a French population, in a case-control study. Methods A total of 1,080 patients with exudative AMD and 406 controls were recruited and genotyped for Y402H of complement factor H (CFH), rs10490924 of age-re...

  17. Zinc-induced self-association of complement C3b and Factor H: implications for inflammation and age-related macular degeneration.

    OpenAIRE

    Nan, R.; Tetchner, S; Rodriguez, E.; Pao, P. J.; Gor, J.; Lengyel, I; Perkins, S J

    2013-01-01

    The sub-retinal pigment epithelial deposits (sRPEds) that are a hallmark of age-related macular degeneration (AMD) contain both C3b and mM levels of zinc. C3 is the central protein of complement, while C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation...

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-06-01

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

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

    International Nuclear Information System (INIS)

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

  20. Intravitreal ranibizumab and bevacizumab therapy for choroidal neovascularization in age-related macular degeneration with extensive pre-existing geographic atrophy

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    Miguel Hage Amaro

    2012-08-01

    Full Text Available PURPOSE: To report the response of choroidal neovascularization to intravitreal ranibizumab or bevacizumab treatment in the setting of age-related macular degeneration with extensive pre-existing geographic atrophy of the retinal pigment epithelium. METHODS: This is a retrospective case series of 11 eyes in ten consecutive patients retrieved from a photographic database. The patients were treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration with pre-existing geographic atrophy. Patients were included if they had geographic atrophy at or adjacent to the foveal center of at least 1 disc area in size that was present before the development of choroidal neovascularization. The best corrected visual acuity and optical coherence tomography analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab or bevacizumab were administered until there was complete resolution of subretinal fluid on optical coherence tomography. Data over the entire follow-up period were analyzed for overall visual and optical coherence tomography changes. RESULTS: The patients received an average of 7 ± 3 intravitreal injections over the treatment period. Seven of 11 eyes had reduced retinal thickening on optical coherence tomography. On average, the central macular thickness was reduced by 72 ± 115 µm. Six of these 7 eyes had improvement of one or more lines of vision and one had no change. The average acuity change for all patients was -0.04 ± 0.46 logMAR units, which corresponded to a gain of 0.2 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with resolution of the subretinal fluid and overall stable visual acuity. CONCLUSIONS: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF agent (ranibizumab or bevacizumab for choroidal neovascularization in age-related macular degeneration with pre

  1. The methodological quality of systematic reviews comparing intravitreal bevacizumab and alternates for neovascular age related macular degeneration: A systematic review of reviews

    Directory of Open Access Journals (Sweden)

    Pradeep Paul George

    2014-01-01

    Full Text Available Objective: To systematically collate and evaluate the evidence from recent SRs of bevacizumab for neo-vascular age related macular degeneration. Materials and Methods: Literature searches were carried out in Medline, Embase, Cochrane databases for all systematic reviews (SRs on the effectiveness of bevacizumab for neo-vascular age related macular degeneration, published between 2000 and 2013. Titles and abstracts were assessed against the inclusion/exclusion criteria using Joanna Briggs Institute (JBI study eligibility form. Data was extracted using the JBI data extraction form. The quality of the SRs was assessed using JBI critical appraisal checklist for SRs. Decisions on study eligibility and quality were made by two reviewers; any disagreements were resolved by discussion. Results: Nine relevant reviews were identified from 30 citations, of which 5 reviews fulfilled the review′s inclusion criteria. All 5 reviews showed bevacizumab to be effective for neovascular AMD in the short-term when used alone or in combination with PDT or Pegaptanib. The average quality score of the reviews was 7; 95% confidence interval 6.2 to 7.8 (maximum possible quality score is 10. The selection and publication bias were not addressed in all included reviews. Three-fifth of the reviews had a quality score of 7 or lower, these reviews had some methodological limitations, search strategies were only identified in 2 (40% reviews, independent study selection and quality assessment of included studies (4 (80% were infrequently performed. Conclusion: Overall, the reviews on the effectiveness of intravitreal/systemic bevacizumab for neovascular age-related macular generation (AMD received good JBI quality scores (mean score = 7.0 points, with a few exceptions. The study also highlights the suboptimal reporting of SRs on this topic. Reviews with poor methodology may limit the validity of the reported results; hence efforts should be made to improve the design

  2. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration

    International Nuclear Information System (INIS)

    Purpose: Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray-induced changes in neovasculature microcirculation. Methods and materials: Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured. Results: Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values. Conclusion: These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose

  3. The quality of life impact of peripheral versus central vision loss with a focus on glaucoma versus age-related macular degeneration

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    Keith Evans

    2009-07-01

    Full Text Available Keith Evans1, Simon K Law2, John Walt3, Patricia Buchholz4, Jan Hansen31Global Health Outcomes, Wolters Kluwer Health, Chester, United Kingdom; 2Jules Stein Eye Institute, Los Angeles, CA, USA; 3Global Health Outcomes Strategy and Research, Allergan Inc., Irvine, CA, USA; 4Health Economics, Pricing, and Reimbursement, Allergan GmbH, Ettlingen, GermanyPurpose: It is well accepted that conditions that cause central vision loss (CVL have a negative impact on functional ability and quality of life (QoL, but the impact of diseases that cause peripheral vision loss (PVL is less well understood. Focusing on glaucoma and age-related macular degeneration (ARMD, the effects of CVL and PVL on QoL were compared. Methods: A systematic literature review of publications reporting QoL in patients with CVL or PVL identified 87 publications using four generic (Short-Form Health Survey-36 and -12, EuroQoL EQ-5D and Sickness Impact Profile and five vision-specific (National Eye Institute Visual Function Questionnaire-51, -39, and -25, Impact of Vision Impairment and Visual Function-14 QoL instruments; 33 and 15 publications reported QoL in ARMD and glaucoma, respectively.Results: QoL was impaired to a similar extent by diseases associated with PVL and CVL, but different domains were affected. In contrast to ARMD, mental aspects appeared to be affected more than physical aspects in patients with glaucoma.Conclusions: The differential impact upon QoL might be a function of the pathology of the diseases, for example potential for blindness and better ability to perform physical tasks due to retention of central vision may explain these observations in glaucoma.Keywords: vision loss, quality of life, glaucoma, age-related macular degeneration, diabetic macular edema, cataracts

  4. A Delphi Study to Detect Deficiencies and Propose Actions in Real Life Treatment of Neovascular Age-Related Macular Degeneration

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    Alfredo García-Layana

    2014-01-01

    Full Text Available Purpose. Spanish retina specialists were surveyed in order to propose actions to decrease deficiencies in real-life neovascular age macular degeneration treatment (nv-AMD. Methods. One hundred experts, members of the Spanish Vitreoretinal Society (SERV, were invited to complete an online survey of 52 statements about nv-AMD management with a modified Delphi methodology. Four rounds were performed using a 5-point Linkert scale. Recommendations were developed after analyzing the differences between the results and the SERV guidelines recommendations. Results. Eighty-seven specialists completed all the Delphi rounds. Once major potential deficiencies in real-life nv-AMD treatment were identified, 15 recommendations were developed with a high level of agreement. Consensus statements to reduce the burden of the disease included the use of treat and extend regimen and to reduce the amount of diagnostic tests during the loading phase and training technical staff to perform these tests and reduce the time between relapse detection and reinjection, as well as establishing patient referral protocols to outside general ophthalmology clinics. Conclusion. The level of agreement with the final recommendations for nv-AMD treatment among Spanish retinal specialist was high indicating that some actions could be applied in order to reduce the deficiencies in real-life nv-AMD treatment.

  5. Angiopoietin-like Protein 2 Is a Multistep Regulator of Inflammatory Neovascularization in a Murine Model of Age-related Macular Degeneration.

    Science.gov (United States)

    Hirasawa, Manabu; Takubo, Keiyo; Osada, Hideto; Miyake, Seiji; Toda, Eriko; Endo, Motoyoshi; Umezawa, Kazuo; Tsubota, Kazuo; Oike, Yuichi; Ozawa, Yoko

    2016-04-01

    Choroidal neovascularization (CNV) is a pathogenic process of age-related macular degeneration, a vision-threatening disease. The retinal pigment epithelium and macrophages both influence CNV development. However, the underlying mechanisms remain obscure. Here, we focus on Angptl2 (angiopoietin-like protein 2), a cytokine involved in age-related systemic diseases. Angptl2 was originally identified as an adipocytokine and is also expressed in the eye. Using a laser-induced CNV model, we found thatAngptl2KO mice exhibited suppressed CNV development with reduced macrophage recruitment and inflammatory mediator induction. The mediators monocyte chemotactic protein-1, interleukin-1β (Il-1β),Il-6, matrix metalloprotease-9 (Mmp-9), and transforming growth factor-β1 (Tgf-β1) that were up-regulated during CNV development were all suppressed in the retinal pigment epithelium-choroid of CNV models generated in theAngptl2KO mice. Bone marrow transplantation using wild-type and KO mice suggested that both bone marrow-derived and host-derived Angptl2 were responsible for macrophage recruitment and CNV development. Peritoneal macrophages derived fromAngptl2KO mice expressed lower levels of the inflammatory mediators. In the wild-type peritoneal macrophages and RAW264.7 cells, Angptl2 induced the mediators via integrins α4 and β2, followed by the downstream activation of NF-κB and ERK. The activation of NF-κB and ERK by Angptl2 also promoted macrophage migration. Therefore, Angptl2 from focal tissue might trigger macrophage recruitment, and that from recruited macrophages might promote expression of inflammatory mediators including Angptl2 in an autocrine and/or paracrine fashion to facilitate CNV development. Angptl2 might therefore represent a multistep regulator of CNV pathogenesis and serve as a new therapeutic target for age-related macular degeneration. PMID:26839315

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

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    M. Piccardi

    2012-01-01

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

  7. CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice.

    Science.gov (United States)

    Sennlaub, Florian; Auvynet, Constance; Calippe, Bertrand; Lavalette, Sophie; Poupel, Lucie; Hu, Shulong J; Dominguez, Elisa; Camelo, Serge; Levy, Olivier; Guyon, Elodie; Saederup, Noah; Charo, Israel F; Rooijen, Nico Van; Nandrot, Emeline; Bourges, Jean-Louis; Behar-Cohen, Francine; Sahel, José-Alain; Guillonneau, Xavier; Raoul, William; Combadiere, Christophe

    2013-11-01

    Atrophic age-related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2(+) inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2(+) monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD. PMID:24142887

  8. CCR2+ monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice

    Science.gov (United States)

    Sennlaub, Florian; Auvynet, Constance; Calippe, Bertrand; Lavalette, Sophie; Poupel, Lucie; Hu, Shulong J; Dominguez, Elisa; Camelo, Serge; Levy, Olivier; Guyon, Elodie; Saederup, Noah; Charo, Israel F; Van Rooijen, Nico; Nandrot, Emeline; Bourges, Jean-Louis; Behar-Cohen, Francine; Sahel, José-Alain; Guillonneau, Xavier; Raoul, William; Combadiere, Christophe

    2013-01-01

    Atrophic age-related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2+ inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2+ monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD. PMID:24142887

  9. Advances in the management of macular degeneration

    OpenAIRE

    Singer, Michael

    2014-01-01

    Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future lo...

  10. An eye on nutrition: The role of vitamins, essential fatty acids, and antioxidants in age-related macular degeneration, dry eye syndrome, and cataract.

    Science.gov (United States)

    McCusker, Meagen M; Durrani, Khayyam; Payette, Michael J; Suchecki, Jeanine

    2016-01-01

    Visual impairment is a global epidemic. In developing countries, nutritional deficiency and cataracts continue to be the leading cause of blindness, whereas age-related macular degeneration (AMD) and cataracts are the leading causes in developed nations. The World Health Organization has instituted VISION 2020: "The Right to Sight" as a global mission to put an end to worldwide blindness. In industrialized societies, patients, physicians, researchers, nutritionists, and biochemists have been looking toward vitamins and nutrients to prevent AMD, cataracts, and dry eye syndrome (DES). Nutrients from the AREDS2 study (lutein, zeaxanthin, vitamin C, vitamin E, zinc, copper, eicosapentanoic acid [EPA], and docosahexanoic acid [DHA]) set forth by the National Institutes of Health remain the most proven nutritional therapy for reducing the rate of advanced AMD. Omega-3 fatty acids, especially DHA, have been found to improve DES in randomized clinical trials. Conflicting results have been seen with regard to multivitamin supplementation on the prevention of cataract. PMID:26903189

  11. Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population: letter to the editor

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    Stewart MW

    2015-09-01

    Full Text Available Michael W Stewart Department of Ophthalmology, Mayo Clinic Florida, Jacksonville, FL, USA In their recently published manuscript entitled “Visual outcomes of age-related macular degeneration patients undergoing intravitreal ranibizumab monotherapy in an urban population” Basheer et al1 reported on the prospectively acquired results of 123 eyes (106 patients treated for 2 years with ranibizumab as needed. Visual acuity (VA outcomes from this series were summarized by the following statement: “Although our results, and those from other clinical settings, do not quite match the degree of vision preservation and gain as the large clinical trials, they are not dramatically dissimilar”.1 Unfortunately, the authors provide no statistical analysis to support this statement.View original paper by Basheer and colleagues.

  12. AGE-RELATED MACULAR DEGENERATION IS A VASCULAR DISEASE, PART OF VASCULOPATHY: HOLISTIC APPROACH OF THE AMD’S PATHOPHYSIOLOGY, PREVENTION AND PREVENTIVE TREATMENT

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    Tamás Fischer

    2012-12-01

    Full Text Available The endothelial system assures unhindered functioning and stability of the internal milieu maintaining vascular health and protecting against vascular injury, noxa. by producing, synthesising and excreting various substances: vasodilators and vasoconstrictors, growth factors and their inhibitors, pro-inflammatory and antiinflammatory agents, pro-thrombotic and fibrinolytic factors, and by keeping them in a strict equilibrium: endothelial dysfunction is the change of these properties, what is inappropriate with regard to the preservation of organ function. In the genesis and later development of age-related macular degeneration (AMD, endothelial dysfunction (ED has a crucial key role. AMD-risk factors often are identical wih the risk factors of (cardiovascular (CV diseases, so the two conditions have a similar pathogenesis. These risk factors lead to vascular injury through the same mechanism of actions, by inducing oxidative stress (OS → ED!: harm (noxa, i.e. |AMD| risk factors → oxidative stress [OS] → endothelial activation [EA], endothlial dysfunction [ED], respectively → vacular injury, vascular disease. Disordered function of endothelium in the vessels supplying the affected ocular structures with blood (ED have a key role in the genesis and development of age-related macular degeneration. Wall of blood vessels including thoose in choroids may be triggered by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic influences-impacts-stimuli (noxa, against which protracted response, the so-called host defense response may develop, and in consequence of this, vascular damage pathological consecutive changes ending in AMD, ultimately, may develop. As the human vascular system is uniform and consubstantial, the medicines/non-medicinal methods desribed below [the RAAS-inhibiting (1 angiotensin converting enzyme ihibitors and (2 angiotensinreceptor blockers |AT1 receptor blocker

  13. Transconjunctival sutureless vitrectomy with tissue plasminogen activator, gas and intravitreal bevacizumab in the management of predominantly hemorrhagic age-related macular degeneration

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    Luis Arias

    2010-02-01

    Full Text Available Luis Arias1,2, Jordi Monés11Institut de la Màcula i de la Retina, Centro Médico Teknon, Barcelona; 2Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, BarcelonaPurpose: To determine the efficacy and safety of treating predominantly hemorrhagic age-related macular degeneration (AMD with transconjunctival sutureless vitrectomy (TSV, tissue plasminogen activator (tPA, sulphur hexafluoride (SF6, and intravitreal bevacizumab.Methods: Retrospective study, consecutive case series. Patients with acute hemorrhagic AMD treated with 25- or 23-gauge TSV, subretinal or intravitreal tPA, fluid-air-SF6 exchange and intravitreal injection of bevacizumab. All operations were performed within the first 5 days after the start of symptoms, which consisted of visual acuity (VA loss and central scotoma.Results: Fifteen eyes from 15 patients were included. The patients’ mean age was 79.6 years, and the mean follow-up was 11.8 months. Five patients (33% were receiving oral anticoagulant treatment. At baseline, the mean VA (logMAR values was 1.5 (20/640 Snellen equivalent. At the last follow-up visit, the mean VA was 1.1 (20/250 (P < 0.0001; paired t-test. The submacular hemorrhage was successfully displaced in all the cases. Complications consisted of three cases of vitreous hemorrhage and a tear or the retinal pigment epithelium. Twelve cases (80% did not require further treatment during the follow-up period.Conclusion: A surgical approach with 25- or 23-gauge TSV, tPA, SF6 and intravitreal bevacizumab is an efficacious and safe procedure in patients with hemorrhagic AMD. Early treatment is advisable for obtaining the optimal outcome.Keywords: Hemorrhagic age-related macular degeneration, tissue plasminogen activator, intravitreal bevacizumab; transconjunctival sutureless vitrectomy

  14. Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

    Science.gov (United States)

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2015-11-01

    Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. PMID:26368850

  15. Phase I/II study of proton beam irradiation for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: treatment techniques and preliminary results

    International Nuclear Information System (INIS)

    Purpose: Age-related macular degeneration is the prevalent etiology of subfoveal choroidal neovascularization (CNV). The only effective treatment is laser photocoagulation, which is associated with decreased visual acuity following treatment in most patients. This study assessed both the response of subfoveal CNV to proton beam irradiation and treatment-related morbidity. We evaluated preliminary results in patients treated with an initial dose of 8 Cobalt Gray Equivalents (CGE) using a relative biological effectiveness (RBE) of 1.1. Methods and Materials: Twenty-one patients with subfoveal CNV received proton irradiation to the central macula with a single fraction of 8 CGE; 19 were eligible for evaluation. Treatment-related morbidity was based on Radiation Therapy Oncology Group (RTOG) criteria; response was evaluated by Macular Photocoagulation Study (MPS) guidelines. Fluorescein angiography was performed; visual acuity, contrast sensitivity, and reading speed were measured at study entry and at 3-month intervals after treatment. Follow-up ranged from 6 to 15 months. Results: No measurable treatment-related morbidity was seen during or after treatment. Of 19 patients evaluated at 6 months, fluorescein angiography demonstrated treatment response in 10 (53%); 14 (74%) patients had improved or stable visual acuity. With a mean follow-up of 11.6 months, 11 (58%) patients have demonstrated improved or stable visual acuity. Conclusion: A macular dose of 8 CGE yielded no measurable treatment morbidity in patients studied. Fluorescein nagiography demonstrated that regressed or stabilized lesions were associated with improved visual acuity as compared with MPS results. In the next phase, a dose of 14 CGE in a single fraction will be used to further define the optimal dose fractionation schedule

  16. Animal models in research on age-related macular degeneration%年龄相关性黄斑变性的动物模型

    Institute of Scientific and Technical Information of China (English)

    聂闯; 罗灵; 张卯年

    2015-01-01

    年龄相关性黄斑变性(age-related macular degeneration,AMD)已成为65岁以上人群视力损失的主要原因,是一种年龄、基因、环境等多因素共同作用的慢性疾病,首先表现为Bruch膜的损害,随后影响到视网膜色素上皮和光感受器。随着疾病研究的深入,已发现了越来越多的特殊类型,但是其具体发病机制仍不明确。因此研究者们为了更深入地研究疾病以及研发新的治疗手段建立了各种各样的动物模型。我们复习了国内外经典以及较新的动物模型文献,并按不同疾病类型进行综述,希望为研究者寻找理想的动物实验平台提供思路。%Age-related macular degeneration (AMD) is the leading cause of blindness in the individuals older than 65 years. It is a complex chronic disease influenced by age, genetic and environmental factors. AMD begins in Bruch's membrane and progresses into the retinal pigment epithelium and ultimately the overlying photoreceptors. It has several subtypes. Its etiology still remains unclear and its therapy is still a big challenge. Recently, there are several AMD animal models have been established for research. This article reviews these diversity of animal models, both on their advantages and limitations, in order to provide some details for further study.

  17. Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Erin W. [Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI (United States); Schaumberg, Debra A. [Division of Preventive Medicine, Brigham and Women' s Hospital, Harvard Medical School and Department of Epidemiology, Harvard School of Public Health, Boston, MA (United States); Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT (United States); Park, Sung Kyun, E-mail: sungkyun@umich.edu [Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI (United States); Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI (United States)

    2014-08-15

    Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age-related

  18. Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

    International Nuclear Information System (INIS)

    Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age-related

  19. A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

    Science.gov (United States)

    Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

    2016-05-01

    The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value management of patients with this common degenerative maculopathy.

  20. Sun exposure and visual field damage among children on the Adriatic Island Rab--possible initial risk factor in development of age-related macular degeneration.

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    Vojniković, Bozidar; Micović, Vladimir; Coklo, Miran; Vojniković, Davor

    2009-09-01

    The Adriatic Island Rab, situated in the northern part of the Croatian sea, is more strongly exposed to sunlight (especially from May to October) than the other parts of Croatia and most of the European countries. As consequences of higher solar radiation, significant percentage of Pseudoexfoliation of lens capsula occurs in 15% and fundus picture of AMD (Age-Related Macular Degeneration) in 18% of agriculturalists and fishermen (45-70 years old). We previously presented the first clinical study showing that in AMD the peripheral visual field is also damaged. In this clinical study we examined 68 children (8-15 years old), including following procedures: vision correction, slit lamp examination, visual field in technic of isopters and profile quantitative perimetry (meridian retinal thresholds examination) using Kowa automated perimeter. In 15% of examinees we found strictly foveal "degeneration", and changes of visual fields: higher meridian thresholds and typical changes with invagination of isopters. It is very interesting that these children with damaged visual field and fundus picture do not protect their eyes from the sunlight during summertime. We suggest the possibility of the influence of higher sun radiation as one of the risk factors in the earlier development of future AMD. PMID:19860099

  1. Bilateral visual outcomes and service utilization of patients treated for 3 years with ranibizumab for neovascular age-related macular degeneration

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    Chavan R

    2014-04-01

    Full Text Available Randhir Chavan,1,* Swati Panneerselvam,1,* Parul Adhana,1 Nirodhini Narendran,1 Yit Yang1,2 1Eye Infirmary, New Cross Hospital, Royal Wolverhampton Hospitals NHS Trust Wolverhampton, West Midlands, UK; 2Faculty of Life and Health Sciences, Aston University, Birmingham, UK *These authors contributed equally to this paper Background: The aim of this study was to describe bilateral visual outcomes and the effect of incomplete follow-up after 3 years of ranibizumab therapy for neovascular age-related macular degeneration. Secondarily, the demands on service provision over a 3-year period were described. Methods: Data on visual acuity, hospital visits, and injections were collected over 36 months on consecutive patients commencing treatment over a 9-month period. Visual outcome was determined for 1 all patients, using last observation carried forward for missed visits due to early discontinuation and 2 only those patients completing full 36-month follow-up. Results: Over 3 years, 120 patients cumulatively attended hospital for 1,823 noninjection visits and 1,365 injection visits. A visual acuity loss of <15 letters (L was experienced by 78.2% of patients. For all patients (n=120, there was a mean loss of 1.68 L using last observation carried forward for missing values. Excluding five patients who died and 30 who discontinued follow-up, mean gain was 1.47 L. In bilateral cases, final acuity was on average 9 L better in second eyes compared to first eyes. Also, 91% of better-seeing eyes continued to be the better-seeing eye. Conclusion: We have demonstrated our approach to describing the long-term service provision and visual outcomes of ranibizumab therapy for neovascular age-related macular degeneration in a consecutive cohort of patients. Although there was a heavy burden with very frequent injections and clinic visits, patients can expect a good level of visual stability and a very high chance of maintaining their better

  2. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

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    Sarah Mrejen

    2015-07-01

    Full Text Available With the advent of anti-vascular endothelial growth factor (VEGF therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD, a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes were followed over an average of 3.5 years (range 1–6.6 with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6 (± standard deviation intravitreal anti-VEGF injections/year (range 4–13. The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

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

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    Sudhakar John

    2013-01-01

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

  4. Newly diagnosed exudative age-related macular degeneration treated with pegaptanib sodium monotherapy in US community-based practices: medical chart review study

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    Xu Xiao

    2010-02-01

    Full Text Available Abstract Background Studies have shown that early detection and treatment of neovascular age-related macular degeneration (NV-AMD can delay vision loss and blindness. The objective of this study was to evaluate the efficacy/safety of intravitreal pegaptanib sodium monotherapy in treatment-naïve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices. Methods From seven private US practices, charts were retrospectively reviewed on 73 subjects with previously untreated subfoveal choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after 4/1/2005 through 6/5/2006, receiving ≥4 treatments at 6-week intervals over 21 weeks. Primary endpoint: mean visual acuity (VA change from baseline to month 6. Results 75% of lesions were occult, and 82% were subfoveal. From baseline to month 6, mean VA change was -0.68 lines; 58% and 16% gained ≥0 and ≥3 lines of VA, and 70% were responders ( Conclusion Pegaptanib is effective in real-world patients with treatment-naïve NV-AMD in uncontrolled community-based retina practices.

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

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    Agarwal A

    2015-06-01

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

  6. Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration.

    Science.gov (United States)

    Szatmári-Tóth, M; Kristóf, E; Veréb, Z; Akhtar, S; Facskó, A; Fésüs, L; Kauppinen, A; Kaarniranta, K; Petrovski, G

    2016-01-01

    Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis. PMID:27607582

  7. A Brief Discussion on Lipid Activated Nuclear Receptors and their Potential Role in Regulating Microglia in Age-Related Macular Degeneration (AMD).

    Science.gov (United States)

    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

  8. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review.

    Science.gov (United States)

    Lanzetta, Paolo; Mitchell, Paul; Wolf, Sebastian; Veritti, Daniele

    2013-12-01

    Antivascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of wet age-related macular degeneration (wAMD). Recent research has focused on evaluating competing agents and alternative dosage regimens, providing evidence to help determine optimal treatment strategies. We therefore conducted a review of clinical research studies in wAMD published since 2008 that compared anti-VEGF dosing regimens and therapies; seven studies met our inclusion criteria. Data on baseline disease characteristics, disease outcomes, safety (ocular and systemic) and treatment burden (injection and visit frequencies) were extracted on patients treated with ranibizumab 0.5 mg, bevacizumab 1.25 mg or aflibercept 2.0 mg for up to 2 years. For ranibizumab and bevacizumab, visual and anatomical outcomes at 1 and 2 years were superior using scheduled monthly (or 4 weekly (q4w)) compared with as needed or scheduled quarterly dosing regimens. Treatment outcomes were generally better for both drugs when more aggressive retreatment criteria were used, which resulted in more frequent injections. Bevacizumab, however, was associated with a 30-35% elevated rate of serious systemic adverse events compared with ranibizumab, regardless of dosing interval; further study in larger patient populations will be required to determine the validity of this finding. Intravitreal aflibercept injection every 8 weeks was non-inferior to ranibizumab q4w on all visual and anatomical endpoints at week 52, had a similar safety profile and required five fewer anti-VEGF injections. PMID:23929309

  9. External-beam radiation therapy for age-related macular degeneration. Two years' follow-up results at a total dose of 20 Gy in 10 fractions

    International Nuclear Information System (INIS)

    The efficacy of external-beam radiation therapy (RT) was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration (ARMD). Twenty-one eyes of 18 patients with occult or mixed-type ARMD received a total dose of 20 Gy of 6 MV X-rays in 10 fractions. The follow-up time was 24 months. Fifteen non-treated eyes of 13 patients who had been followed served as a control. In the RT group, visual acuity was improved in three eyes, maintained in 14 eyes, and worsened in four eyes. In the control group, it was not improved in any eyes, was maintained in six eyes, and worsened in nine eyes. The improved or maintained rate in visual acuity was 81% in the RT group and 40% in the control group (p=0.0342). In the RT group, fundoscopic and angiographic findings were improved in five eyes, unchanged in seven eyes, and worsened in nine eyes, while they were not improved in any eyes, unchanged in two eyes, and worsened in 13 eyes in the control group (p=0.0342). RT at a total dose of 20 Gy in 10 fractions is effective for ARMD for at least two years. RT may be effective treatment for occult or mixed-type ARMD compared with the classic type. (author)

  10. Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration.

    Science.gov (United States)

    Koenig, Patrick; Lee, Chingwei V; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F; Fuh, Germaine

    2015-09-01

    The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. PMID:26088137

  11. Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper

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    Miguel Hage Amaro

    2012-12-01

    Full Text Available PURPOSE: To report the response of choroidal neovascularization (CNV to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD with extensive pre-existing geographic atrophy (GA and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF agent (ranibizumab for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti

  12. Serum carboxymethyllysine, an advanced glycation end product, and age-related macular degeneration: the Age, Gene/Environment Susceptibility-Reykjavik Study.

    Science.gov (United States)

    Semba, Richard D; Cotch, Mary Frances; Gudnason, Vilmundur; Eiríksdottir, Gudny; Harris, Tamara B; Sun, Kai; Klein, Ronald; Jonasson, Fridbert; Ferrucci, Luigi; Schaumberg, Debra A

    2014-04-01

    IMPORTANCE Advanced glycation end products have been implicated in the pathogenesis of age-related macular degeneration (AMD). OBJECTIVE To investigate the relationship between serum carboxymethyllysine (CML), a major circulating advanced glycation end product, and AMD in older adults. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of a population-based sample of 4907 older adults (aged ≥66 years) in the Age, Gene/Environment Susceptibility-Reykjavik Study in Iceland. EXPOSURES Serum CML and risk factors for AMD. MAIN OUTCOMES AND MEASURES Early or late AMD, assessed through fundus images taken through dilated pupils using a 45° digital camera and grading for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS Of the 4907 participants, 1025 (20.9%) had early AMD and 276 (5.6%) had late AMD. Mean (SD) serum CML concentrations among adults with no AMD, early AMD, and late AMD (exudative AMD and pure geographic atrophy) were 618.8 (195.5), 634.2 (206.4), and 638.4 (192.0) ng/mL, respectively (to convert to micromoles per liter, multiply by 0.00489; P = .07). Log serum CML (per 1-SD increase) was not associated with any AMD (early and late AMD) (odds ratio = 0.97; 95% CI, 0.90-1.04; P = .44) or with late AMD (odds ratio = 0.94; 95% CI, 0.82-1.08; P = .36) in respective multivariable logistic regression models adjusting for age, sex, body mass index, smoking, and renal function. CONCLUSIONS AND RELEVANCE Higher serum CML concentration had no significant cross-sectional association with prevalent AMD in this large population-based cohort of older adults in Iceland. PMID:24481410

  13. A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

    Science.gov (United States)

    Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

    2016-05-01

    The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

  14. Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration.

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    M Cristina Kenney

    Full Text Available BACKGROUND: Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD. Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt DNA haplogroups (as defined by combinations of mtDNA polymorphisms that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD versus J haplogroup (high risk for AMD. METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19 that was devoid of mitochondrial DNA (Rho0. In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD.

  15. Satisfação do paciente com degeneração macular relacionada à idade após terapia térmica transpupilar Satisfaction of the patient with age-related macular degeneration after transpupillary thermotherapy

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    Jhony de Polo

    2004-04-01

    degeneration (ARMD. METHODS: In a retrospective study we analyzed 23 charts of patients with angiofluoresceinographic diagnosis of age-related macular degeneration submitted to only one application of transpupillary thermotherapy (TTT. Visual acuity was recorded before and one month after the application, and the satisfaction of the patients with the treatment. RESULTS: 23 patients (15 females and 8 males, 53 to 88 years old (mean 74.8 were evaluated. 12 eyes were found with improvement of visual acuity, 6 eyes without alteration of visual acuity, 6 eyes with worse visual acuity. Regarding satisfaction the results were: 4 eyes, very satisfied; 13 eyes, satisfied; 7 eyes, not satisfed, and checking the data we found 3 eyes, very satisfied with the improvement of visual acuity and 1 eye, very satisfied without improvement of VA. Satisfied with improvement of visual acuity there were 7 eyes, satisfied without improvement of VA, 3 eyes and satisfied with worsening of VA, 3 eyes. CONCLUSION: Visual acuity was improved in 12 eyes of the 24 studied eyes; the number of very satisfied patients reached 17 eyes within one month. Observing these results transpupillary thermotherapy may be considered as alternative or adjuvant treatment for age-related macular degeneration.

  16. Assessing quality of life in the treatment of patients with age-related macular degeneration: clinical research findings and recommendations for clinical practice

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    Yuzawa M

    2013-07-01

    Full Text Available Mitsuko Yuzawa,1 Kyoko Fujita,1 Erika Tanaka,2 Edward C Y Wang21Department of Ophthalmology, Nihon University School of Medicine, Surugadai, Kanda, Chiyoda-ku, Tokyo, Japan; 2Health Economics and Outcomes Research, Bayer Yakuhin Ltd, Marunouchi, Chiyoda-ku, Tokyo, JapanBackground: The importance of incorporating quality-of-life (QoL assessments into medical practice is growing as health care practice shifts from a “disease-based” to a “patient-centered” model. The prevalence of age-related macular degeneration (AMD is increasing in today’s aging population. The purpose of this paper is: (1 to discuss, by reviewing the current literature, the impact of AMD on patients’ QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2 to make a recommendation for incorporating QoL into clinical practice.Methods: We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected.Results: AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25 is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA. QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients’ valued activities, which are not captured by a single, numerical VA score.Conclusion: The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease

  17. Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Pia; E.; Leon; Sandro; Saviano; Andrea; Zanei; Marco; R.; Pastore; Elvira; Guaglione; Alessandro; Mangogna; Daniele; Tognetto

    2014-01-01

    ·AIM:Toevaluatethevisualfunctionevolutionofretinal pigment epithelial(RPE) tears in patients with age-related macular degeneration(AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor(anti-VEGF) injection] and the topographic location of the tear after a two-year followup period.·METHODS: A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were: patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included: careful medical history,complete ophthalmological examination, fluorescein angiography(FA), indocyanine green angiography(ICG),autofluorescence and infrared imaging and optical coherence tomography(OCT). Patients were evaluated every month for visual acuity(VA), fundus examination and OCT. Other data reported were: presence of PED,number of injections before the tear, location of the lesion.·RESULTS:Meanfollow-up was24wk(SD±4wk). Atotal of 15 eyes were studied for RPE tear. In 6 cases(40%),the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13cases(86.6%), the RPE tear was associated with pigment epithelial detachment(PED). In 7 cases(46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period(P <0.01) independently of the type or the topographical location of the lesion.·CONCLUSION: RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.

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

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    Chui Ming Gemmy Cheung

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

  19. Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model.

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    Rana Begum

    Full Text Available Inflammation is an umbrella feature of ageing. It is present in the aged retina and many retinal diseases including age-related macular degeneration (AMD. In ageing and in AMD mitochondrial function declines. In normal ageing this can be manipulated by brief exposure to 670 nm light on the retina, which increases mitochondrial membrane potential and reduces inflammation. Here we ask if 670 nm exposure has the same ability in an aged mouse model of AMD, the complement factor H knockout (CFH(-/- where inflammation is a key feature. Further, we ask whether this occurs when 670 nm is delivered briefly in environmental lighting rather than directly focussed on the retina. Mice were exposed to 670 nm for 6 minutes twice a day for 14 days in the form of supplemented environmental light. Exposed animals had significant increase in cytochrome c oxidase (COX, which is a mitochondrial enzyme regulating oxidative phosphorylation.There was a significant reduction in complement component C3, an inflammatory marker in the outer retina. Vimetin and glial fibrillary acidic protein (GFAP expression, which reflect retinal stress in Muller glia, were also significantly down regulated. There were also significant changes in outer retinal macrophage morphology. However, amyloid beta (Aβ load, which also increases with age in the outer retina and is pro-inflammatory, did not change. Hence, 670 nm is effective in reducing inflammation probably via COX activation in mice with a genotype similar to that in 50% of AMD patients even when brief exposures are delivered via environmental lighting. Further, inflammation can be reduced independent of Aβ. The efficacy revealed here supports current early stage clinical trials of 670 nm in AMD patients.

  20. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration

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    Marazita, Mariela C.; Dugour, Andrea; Marquioni-Ramella, Melisa D.; Figueroa, Juan M.; Suburo, Angela M.

    2015-01-01

    Oxidative stress has a critical role in the pathogenesis of Age-related Macular Degeneration (AMD), a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. Stress-induced premature cellular senescence (SIPS) is postulated to contribute to this condition. In this study, we hypothesized that oxidative damage, promoted by endogenous or exogenous sources, could elicit a senescence response in RPE cells, which would in turn dysregulate the expression of major players in AMD pathogenic mechanisms. We showed that exposure of a human RPE cell line (ARPE-19) to a cigarette smoke concentrate (CSC), not only enhanced Reactive Oxygen Species (ROS) levels, but also induced 8-Hydroxydeoxyguanosine-immunoreactive (8-OHdG) DNA lesions and phosphorylated-Histone 2AX-immunoreactive (p-H2AX) nuclear foci. CSC-nuclear damage was followed by premature senescence as shown by positive senescence associated-β-galactosidase (SA-β-Gal) staining, and p16INK4a and p21Waf-Cip1 protein upregulation. N-acetylcysteine (NAC) treatment, a ROS scavenger, decreased senescence markers, thus supporting the role of oxidative damage in CSC-induced senescence activation. ARPE-19 senescent cultures were also established by exposure to hydrogen peroxide (H2O2), which is an endogenous stress source produced in the retina under photo-oxidation conditions. Senescent cells upregulated the proinflammatory cytokines IL-6 and IL-8, the main markers of the senescence-associated secretory phenotype (SASP). Most important, we show for the first time that senescent ARPE-19 cells upregulated vascular endothelial growth factor (VEGF) and simultaneously downregulated complement factor H (CFH) expression. Since both phenomena are involved in AMD pathogenesis, our results support the hypothesis that SIPS could be a principal player in the induction and progression of AMD. Moreover, they would also explain the striking association of this disease

  1. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration

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    Mariela C. Marazita

    2016-04-01

    Full Text Available Oxidative stress has a critical role in the pathogenesis of Age-related Macular Degeneration (AMD, a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. Stress-induced premature cellular senescence (SIPS is postulated to contribute to this condition. In this study, we hypothesized that oxidative damage, promoted by endogenous or exogenous sources, could elicit a senescence response in RPE cells, which would in turn dysregulate the expression of major players in AMD pathogenic mechanisms. We showed that exposure of a human RPE cell line (ARPE-19 to a cigarette smoke concentrate (CSC, not only enhanced Reactive Oxygen Species (ROS levels, but also induced 8-Hydroxydeoxyguanosine-immunoreactive (8-OHdG DNA lesions and phosphorylated-Histone 2AX-immunoreactive (p-H2AX nuclear foci. CSC-nuclear damage was followed by premature senescence as shown by positive senescence associated-β-galactosidase (SA-β-Gal staining, and p16INK4a and p21Waf-Cip1 protein upregulation. N-acetylcysteine (NAC treatment, a ROS scavenger, decreased senescence markers, thus supporting the role of oxidative damage in CSC-induced senescence activation. ARPE-19 senescent cultures were also established by exposure to hydrogen peroxide (H2O2, which is an endogenous stress source produced in the retina under photo-oxidation conditions. Senescent cells upregulated the proinflammatory cytokines IL-6 and IL-8, the main markers of the senescence-associated secretory phenotype (SASP. Most important, we show for the first time that senescent ARPE-19 cells upregulated vascular endothelial growth factor (VEGF and simultaneously downregulated complement factor H (CFH expression. Since both phenomena are involved in AMD pathogenesis, our results support the hypothesis that SIPS could be a principal player in the induction and progression of AMD. Moreover, they would also explain the striking association of this

  2. Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes.

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    Khan, Kamron N; Mahroo, Omar A; Khan, Rehna S; Mohamed, Moin D; McKibbin, Martin; Bird, Alan; Michaelides, Michel; Tufail, Adnan; Moore, Anthony T

    2016-07-01

    Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research. PMID:27173377

  3. Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration

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    Klein Michael L

    2011-07-01

    Full Text Available Abstract Background Age related macular degeneration (AMD is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH, the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD. Methods Human peripheral blood mononuclear cells (PBMCs were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500. Results We show that C5a promotes interleukin (IL-22 and IL-17 expression by human CD4+ T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4+ cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls. Conclusions Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.

  4. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy?

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    Fernández-Vega, Beatriz; Fernández-Vega, Álvaro; Rangel, Carlos Mario; Nicieza, Javier; Villota-Deleu, Eva; Vega, José A.; Sanchez-Avila, Ronald M.

    2016-01-01

    Aims To report a case of wet age-related macular degeneration (wet-AMD) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) drug, for concomitant Crohn's disease. Methods Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment). Best-corrected visual acuity (BCVA) was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg) for a period of 40 months with intervals of 1–6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks). During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes. PMID:27065854

  5. A Case of Sustained Intraocular Pressure Elevation after Multiple Intravitreal Injection of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration

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    Matsubara, Hisashi; Miyata, Ryohei; Kobayashi, Maki; Tsukitome, Hideyuki; Ikesugi, Kengo; Kondo, Mineo

    2016-01-01

    Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.

  6. A level-set method for pathology segmentation in fluorescein angiograms and en face retinal images of patients with age-related macular degeneration

    Science.gov (United States)

    Mohammad, Fatimah; Ansari, Rashid; Shahidi, Mahnaz

    2013-03-01

    The visibility and continuity of the inner segment outer segment (ISOS) junction layer of the photoreceptors on spectral domain optical coherence tomography images is known to be related to visual acuity in patients with age-related macular degeneration (AMD). Automatic detection and segmentation of lesions and pathologies in retinal images is crucial for the screening, diagnosis, and follow-up of patients with retinal diseases. One of the challenges of using the classical level-set algorithms for segmentation involves the placement of the initial contour. Manually defining the contour or randomly placing it in the image may lead to segmentation of erroneous structures. It is important to be able to automatically define the contour by using information provided by image features. We explored a level-set method which is based on the classical Chan-Vese model and which utilizes image feature information for automatic contour placement for the segmentation of pathologies in fluorescein angiograms and en face retinal images of the ISOS layer. This was accomplished by exploiting a priori knowledge of the shape and intensity distribution allowing the use of projection profiles to detect the presence of pathologies that are characterized by intensity differences with surrounding areas in retinal images. We first tested our method by applying it to fluorescein angiograms. We then applied our method to en face retinal images of patients with AMD. The experimental results included demonstrate that the proposed method provided a quick and improved outcome as compared to the classical Chan-Vese method in which the initial contour is randomly placed, thus indicating the potential to provide a more accurate and detailed view of changes in pathologies due to disease progression and treatment.

  7. Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study.

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    Jennifer L Y Yip

    Full Text Available To examine the cross sectional and longitudinal relationship between cardiovascular risk factors and age-related macular degeneration (AMD in a large British cohort study.The EPIC Norfolk Eye study is nested in a larger prospective cohort study. Data on cardiovascular risk factors were collected at baseline (1993-1997 and follow up (2006-2011 via clinical examination, validated lifestyle questionnaires and serum blood samples. AMD was ascertained using standardised grading of fundus photographs at the follow up. Logistic regression was used to examine associations between baseline and follow up risk factors with AMD.5,344 pairs (62.0% of total 8623 of fundus photographs were of sufficient quality for grading of AMD in participants with mean age of 67.4 years old (range 44-91 at diagnosis. There were 28 cases of late AMD (0.5%, 95% confidence interval (CI=0.3-0.8% and 645 cases of early AMD (12.1%, 95%CI=11.2-13.0.%. In multivariable analysis, older people with higher levels of baseline high density lipoprotein- cholesterol (HDL-C and C-reactive protein (CRP were more likely to have any signs of AMD, after adjusting for sex, education, smoking, and systolic blood pressure. In cross sectional analysis, only older age and higher HDL were significantly associated with AMD.We have found that older age and higher levels of CRP and HDL-C were associated with increased odds of AMD in this population in the longitudinal analysis, but older age and HDL-C, not CRP was significantly associated with AMD in the cross sectional analysis. The prevalence of AMD in this cohort was low compared to other cohorts in Europe, the US and Australia, and probably reflects the some selection biases in follow up participation as well as the low rate of smoking among our healthy participants.

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

    Science.gov (United States)

    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. PMID:25680934

  9. Subretinal AAV2.COMP-Ang1 suppresses choroidal neovascularization and vascular endothelial growth factor in a murine model of age-related macular degeneration.

    Science.gov (United States)

    Lambert, Nathan G; Zhang, Xiaohui; Rai, Ruju R; Uehara, Hironori; Choi, Susie; Carroll, Lara S; Das, Subrata K; Cahoon, Judd M; Kirk, Brian H; Bentley, Blaine M; Ambati, Balamurali K

    2016-04-01

    To assess whether Tie2-mediated vascular stabilization ameliorates neovascular age-related macular degeneration (AMD), we investigated the impact of adeno-associated virus-mediated gene therapy with cartilage oligomeric matrix protein angiopoietin-1 (AAV2.COMP-Ang1) on choroidal neovascularization (CNV), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF) in a mouse model of the disease. We treated mice with subretinal injections of AAV2.COMP-Ang1 or control (AAV2.AcGFP, AAV2.LacZ, and phosphate-buffered saline). Subretinal AAV2 localization and plasmid protein expression was verified in the retinal pigment epithelium (RPE)/choroid of mice treated with all AAV2 constructs. Laser-assisted simulation of neovascular AMD was performed and followed by quantification of HIF, VEGF, and CNV in each experimental group. We found that AAV2.COMP-Ang1 was associated with a significant reduction in VEGF levels (29-33%, p < 0.01) and CNV volume (60-70%, p < 0.01), without a concomitant decrease in HIF1-α, compared to all controls. We concluded that a) AAV2 is a viable vector for delivering COMP-Ang1 to subretinal tissues, b) subretinal COMP-Ang1 holds promise as a prospective treatment for neovascular AMD, and c) although VEGF suppression in the RPE/choroid may be one mechanism by which AAV2.COMP-Ang1 reduces CNV, this therapeutic effect may be hypoxia-independent. Taken together, these findings suggest that AAV2.COMP-Ang1 has potential to serve as an alternative or complementary option to anti-VEGF agents for the long-term amelioration of neovascular AMD. PMID:26775053

  10. Three-year follow-up of ranibizumab treatment of wet age-related macular degeneration: influence of baseline visual acuity and injection frequency on visual outcomes

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    Razi F

    2016-02-01

    Full Text Available Faraz Razi,1 Adnaan Haq,2 Prabhu Tonne,3 Maharatnam Logendran3 1Department of Paediatrics, Basingstoke and North Hampshire Hospital, Basingstoke, UK; 2Department of Ophthalmology, Leicester General Hospital, Leicester, UK; 3Department of Ophthalmology, Northampton General Hospital, Northampton, UK Purpose: To determine the effect of ranibizumab on visual acuity (VA following a 3-year treatment period for patients diagnosed with wet age-related macular degeneration. To establish whether baseline VA and injection frequency influence visual outcomes. Patients and methods: Retrospective review of 70 patients (76 eyes treated with 0.5 mg intravitreal ranibizumab for 3 consecutive months, and pro re nata thereafter (three + pro re nata protocol, over a 3-year period. VA was measured using Early Treatment Diabetic Retinopathy Study (ETDRS charts at baseline, 12, 24, and 36 months. The number of injections administered at the end of years 1, 2, and 3 were also recorded. Eyes were stratified according to baseline VA, as well as the number of injections administered at the end of year 1. Linear regression analysis determined the relationship between VA and both baseline VA and injection frequency. P<0.05 was considered statistically significant. Results: At 36 months, VA improved by a mean of 5.3 ETDRS letters (P=0.002, with 29% of eyes (n=22 demonstrating a clinically significant improvement in VA (gain of ≥15 ETDRS letters. Improvements in VA from baseline to 36 months were inversely proportional to the baseline VA (R=0.414, P=<0.001. A positive correlation was observed between injection frequency and change in VA from baseline to 36 months (R=0.244, P=0.036. Conclusion: Mean improvement in VA is inversely proportional to baseline VA, and directly proportional to injection frequency. Keywords: long-term results, Lucentis, neovascular AMD

  11. Delay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration

    Science.gov (United States)

    LIM, JONATHAN H.; WICKREMASINGHE, SANJEEWA S.; XIE, JING; CHAUHAN, DEVINDER S.; BAIRD, PAUL N.; ROBMAN, LUBA D.; HAGEMAN, GREGORY; GUYMER, ROBYN H.

    2016-01-01

    PURPOSE To investigate the potential influences that affect visual acuity (VA) outcome in a clinic-based cohort of age-related macular degeneration (AMD) patients undergoing anti–vascular endothelial growth factor (anti-VEGF) treatment for choroidal neovascularization. DESIGN Prospective interventional case series. METHODS Patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were prospectively recruited. A detailed questionnaire was given to patients at time of enrollment, to collect information relating to demographics, history of visual symptoms, visual acuity (VA), and treatment scheduling. Delay from symptoms to treatment (“Treatment delay”) was measured in terms of weeks and analyzed in tertiles. Information pertaining to treatment outcomes was collected over a 6-month period. RESULTS One hundred eighty-five eyes of 185 patients were recruited into the study. Longer delay from first symptoms suggestive of CNV to first injection was a significant predictor (P = .015) of poorer treatment outcome, when controlling for age, sex, and baseline VA. Patients with a delay in treatment of 21 weeks or more compared to a delay of 7 weeks or less had an odds ratio of 2.62 (1.20, 5.68) for worsening vision after treatment. CONCLUSIONS Patients experiencing a longer delay between their first symptoms of CNV and their first anti-VEGF treatment have a significantly lower chance of improving vision at 6 months following anti-VEGF therapy. It is critical that this information reach those at potential vision loss from AMD, in order that prompt treatment may be instituted, to maximize the benefits of anti-VEGF treatment. PMID:22245460

  12. Macular degeneration - age-related

    Science.gov (United States)

    ... wet AMD, your doctor may recommend: Laser surgery (laser photocoagulation) -- a small beam of light destroys the leaking, abnormal blood vessels. Photodynamic therapy -- a light activates a drug that is injected ...

  13. Vitaminas e antioxidantes na degeneração macular relacionada à idade Vitamins and antioxidants in age-related macular degeneration

    OpenAIRE

    Pedro Durães Serracarbassa

    2006-01-01

    O autor descreve os efeitos bioquímicos e estruturais das vitaminas e antioxidantes na retina. Apresenta as principais substâncias presentes na dieta alimentar e na suplementação vitamínica envolvidas na gênese da degeneração macular relacionada à idade. Relata ainda os resultados de estudos prospectivos multicêntricos relacionados ao assunto, por meio de revisão bibliográfica.The author describes biochemical and structural effects of vitamins and antioxidants on the retina. The main substanc...

  14. American Macular Degeneration Foundation

    Science.gov (United States)

    ... of Macular Degeneration The Eye as a Camera Anatomy of a Normal Human Eye ADA and Your Legal Protection AMD Treatment ... Amsler Grid Ten Questions to Ask Your Doctor Anatomy of a Normal Human Eye Disclaimer Privacy Policy Americans with Disabilities Act ...

  15. Macular carotenoids and age-related maculopathy

    OpenAIRE

    O'Connell, E; Neelam, K.; Nolan, John; Eong, K. G. A.; BEATTY, S

    2006-01-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary...

  16. Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

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    Sanna P Seitsonen

    Full Text Available BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD, the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9; non-AMD controls and OR 2.79, p = 2.78 x 10(-19, blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls, respectively. Previously, we have shown a strong association between complement factor H (CFH Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression model, a synergy index (departure-from-additivity model and the mutual information method (MI, suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI index.

  17. A common complement C3 variant is associated with protection against wet age-related macular degeneration in a Japanese population.

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    Suiho Yanagisawa

    Full Text Available BACKGROUND: Genetic variants in the complement component 3 gene (C3 have been shown to be associated with age-related macular degeneration (AMD in Caucasian populations of European descent. In particular, a nonsynonymous coding variant, rs2230199 (R102G, is presumed to be the most likely causal variant in the C3 locus based on strong statistical evidence for disease association and mechanistic functional evidence. However, the risk allele is absent or rare (<1% in Japanese and Chinese populations, and the association of R102G with AMD has not been reported in Asian populations. Genetic heterogeneity of disease-associated variants among different ethnicities is common in complex diseases. Here, we sought to examine whether other common variants in C3 are associated with wet AMD, a common advanced-stage manifestation of AMD, in a Japanese population. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 13 tag single nucleotide polymorphisms (SNPs that capture the majority of common variations in the C3 locus and tested for associations between these SNPs and wet AMD in a Japanese population comprising 420 case subjects and 197 controls. A noncoding variant in C3 (rs2241394 exhibited statistically significant evidence of association (allelic P = 8.32 × 10(-4; odds ratio = 0.48 [95% CI = 0.31-0.74] for the rs2241394 C allele. Multilocus logistic regression analysis confirmed that the effect of rs2241394 was independent of the previously described loci at ARMS2 and CFH, and that the model including variants in ARMS2 and CFH plus C3 rs2241394 provided a better fit than the model without rs2241394. We found no evidence of epistasis between variants in C3 and CFH, despite the fact that they are involved in the same biological pathway. CONCLUSIONS: Our study provides evidence that C3 is a common AMD-associated locus that transcends racial boundaries and provides an impetus for more detailed genetic characterization of the C3 locus in Asian populations.

  18. Investigation of a {sup 90}Sr/{sup 90}Y source for intra-ocular treatment of wet age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, Shannon M.; Micka, John A.; DeWerd, Larry A. [University of Wisconsin Medical Radiation Research Center, Madison, Wisconsin 53705 (United States)

    2009-10-15

    Purpose: The purpose of this study is to perform an extensive investigation of an approximately 2.5 mm long {sup 90}Sr/{sup 90}Y source designed for treating wet age-related macular degeneration. Methods: As part of this investigation, a NIST-traceable absorbed dose to water calibration technique was established, and a source deployment verification test was developed. The influence of treatment cannula construction tolerance on the measurements as well as the dose delivered to the patient was investigated using the Monte Carlo code MCNP5. Variation between production cannulae was quantified experimentally using a well-type ionization chamber, and additional measurements along with Monte Carlo calculations of the collimating insert used for source deployment verification were performed to validate the model. Results: Maximum variation in the integrated target dose was seen when the source was shifted laterally within the treatment cannula. For the well chamber measurements, the observed standard deviation in ionization current for a single source placed in different reference cannulae was {+-}0.3%, with a maximum observed range of less than {+-}0.5%. Clinical cannulae in the collimating insert showed an average of 17.8%{+-}0.4% of the reference signal when sources were fully deployed compared to 18.5% predicted by Monte Carlo calculations. This discrepancy has been attributed primarily to construction of the collimator since the collimation gap was observed to be approximately 0.025-0.075 mm smaller than specified. Construction tolerance of the well chamber insert as well as position tolerance of the cannula tip were both investigated, and their influence on the predicted signal was quantified. Additional measurements along with Monte Carlo based calculations of the collimating insert with polyethylene spacers added to the setup were performed to validate the Monte Carlo model. The shimmed Monte Carlo and measured data agree to within 1%, which is a magnitude

  19. Laser therapy and macular degeneration

    Science.gov (United States)

    Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania

    2001-10-01

    Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.

  20. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration

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    Morrison Margaux A

    2011-10-01

    Full Text Available Abstract Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1, and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001. Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OHD] was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance. Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1 in this same family-based cohort. Initial

  1. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration.

    Science.gov (United States)

    Morrison, Margaux A; Silveira, Alexandra C; Huynh, Nancy; Jun, Gyungah; Smith, Silvia E; Zacharaki, Fani; Sato, Hajime; Loomis, Stephanie; Andreoli, Michael T; Adams, Scott M; Radeke, Monte J; Jelcick, Austin S; Yuan, Yang; Tsiloulis, Aristoteles N; Chatzoulis, Dimitrios Z; Silvestri, Giuliana; Kotoula, Maria G; Tsironi, Evangelia E; Hollis, Bruce W; Chen, Rui; Haider, Neena B; Miller, Joan W; Farrer, Lindsay A; Hageman, Gregory S; Kim, Ivana K; Schaumberg, Debra A; DeAngelis, Margaret M

    2011-10-01

    Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD) and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH) and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1), and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001). Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance. Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1) in this same family-based cohort. Initial findings were then

  2. Complicações na facoemulsificação interferem no aparecimento da degeneração macular relacionada à idade? Does phacoemulsification complications interfere in the appearance of age related macular degeneration?

    Directory of Open Access Journals (Sweden)

    Angela Bettarello

    2007-08-01

    Full Text Available OBJETIVO: Avaliar se uma cirurgia de catarata por facoemulsificação com complicação intra-operatória é um fator de risco para o desenvolvimento de degeneração macular relacionada à idade. MÉTODOS: Estudo retrospectivo longitudinal tipo caso-controle com revisão dos prontuários de 1150 pacientes submetidos à facectomia no período de 1995 a 1999, realizadas por apenas um cirurgião (T.C.. Para cálculo estatístico foram utilizados o Qui-quadrado com correção de Yates, Teste Exato de Fisher e Teste de Mann-Whitney, com intervalo de confiança de 95% (p PURPOSE: To estimate if a complicated phacoemulsification is a risk factor for developing age related macular degeneration. METHODS: Retrospective case-control study with review of records of 1150 patients, that underwent phacoemulsification surgery between 1995 and 1999, performed by a single surgeon (T.C. Qui square test, Fisher exact test, and Mann-Whitney test were used to perform statistical analysis. RESULTS: There were 224 participants who had cataract surgery on 297 eyes, and from this total, 240 were with no complication and 57 were complicated surgery. In the female group there were a total of 38 complicated surgery, and ten of those developed ARMD. (p = 0,0509. In the male group one in 19 of the eyes that have complicated surgery developed ARMD (p = 0,5737. CONCLUSION: There were no statistically significant increase in the incidence of ARMD in eyes that have complicated surgery, however more research is necessary to clarify the pathogeny of this desease.

  3. Genetics Home Reference: Stargardt macular degeneration

    Science.gov (United States)

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

  4. Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background The present study was undertaken to replicate the associations of representative polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Hart Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes. Methods An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms (SNPs) loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and directresequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis. Results The C risk allele frequencies for CFH Y402H (rs1061170) in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians (P<0.001). Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio (OR) of 3.23 (1.36-5.07). However, the population attributable risk (PAR) of C allele was only 3.3% (1.4%-4.3%). rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 (1.21-5.45) and 4.76 (2.15-10.55) respectively, with correspondent PARs of 28.3% (2.0%-40.5%) and 38.2% (21.8%-45.4%). rs11200638 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD (OR=3.98, 1.88-8.43) with PAR of 38.9% (24.3%-45.8%). Education status and

  5. Spectral thresholds in macular degeneration.

    OpenAIRE

    S. L. ALVAREZ; King-Smith, P E; Bhargava, S K

    1983-01-01

    Spectral sensitivities were measured in 18 normal eyes, 9 eyes in patients with senile macular degeneration, 4 patients with Stargardt's juvenile macular degeneration (JMD), and 2 patients without conclusive signs--that is, genetic or morphological abnormalities--to indicate the cause of loss of central vision. Spectral sensitivity, testing for which included measurements on white, yellow, purple, and blue backgrounds, is here used as an aid in differential diagnosis for cases of macular dege...

  6. The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

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    I. V. Vorobyova

    2014-01-01

    Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

  7. Macular carotenoids and age-related maculopathy.

    Science.gov (United States)

    O'Connell, Eamonn; Neelam, Kumari; Nolan, John; Au Eong, Kah-Guan; Beatty, Stephan

    2006-11-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary supplementation with these carotenoids might prevent, delay, or modify the course of ARM. This article discusses the scientific rationale supporting the hypothesis that L and Z are protective against ARM, and presents the recent evidence germane to this theory. PMID:17160199

  8. 中国老年性黄斑变性临床诊断治疗路径%Clinical Pathway of Age-related Macular Degeneration in China

    Institute of Scientific and Technical Information of China (English)

    中华医学会眼科学分会眼底病学组中国老年性黄斑变性临

    2013-01-01

    Objectives The prevalence of age-related macular degeneration (AMD) is rising in China in recent years,and there are more and more drug treatment modalities for this disease.However,all over the country many ophthalmologists have only limited knowledge of prevention and intervention of AMD.In most hospitals the management of AMD is personal experience-based without consensus.It is urgent to propose a standardized clinical pathway for AMD in China.Methods The clinical guideline and clinical pathway development committee of AMD is established under the Chinese Ocular Fundus Diseases Society.The committee proposed the Chinese AMD clinical pathway (hereinafter referred to as "clinical pathway"),based on existed international guidelines,and updated clinical research evidence,the specific types of AMD and the current socio-economic status in China.Results This clinical pathway was developed on the basis of the clinical stages and clinical types of AMD,including the choice of examination items,treatment methods,follow-up and low vision aids.The clinical pathway was designed in flow sheets,which is easy to understand and implement for ophthalmologists,thus to standardize AMD clinical management procedures.Conclusions The clinical pathway,which followed the basic principles of evidence-based medicine and combined with the actual demands of patients with AMD in China,provides principle guidance for the diagnosis and treatment of AMD.The clinical pathway was designed to meet the requirements of the majority of AMD patients; clinicians should also consider individual situations of patients,available treatment options,the patient's affordability and other factors when making treatment decisions.%目的 近年来,中国老年性黄斑变性(AMD)患病率不断上升,药物治疗手段快速发展,中国各地眼科医师对AMD的干预意识与知识的普及率有待提高,各地区各层级医院对AMD的诊断与治疗仍以自己的经验积累为主,需要规范化的

  9. Avaliação da perimetria macular em pacientes com degeneração macular relacionada à idade por meio do oftalmoscópio de rastreamento a laser Evaluation of macular perimetry in patients with age-related macular degeneration using the scanning laser ophthalmoscope

    Directory of Open Access Journals (Sweden)

    Lúcio Moraes

    2007-10-01

    Full Text Available OBJETIVOS: Verificar a relação entre alterações anatômicas (drusas duras, drusas moles, hiperpigmentação, neovasos, descolamento do epitélio pigmentado da retina, hipopigmentação e atrofia coriorretiniana e a sensibilidade à luz em pacientes com degeneração macular relacionada à idade (DMRI; analisar a sensibilidade macular em áreas com ausência de lesões anatômicas nos pacientes com DMRI comparando-as ao grupo de controles, para avaliar a existência ou não de lesão funcional em área sem lesão anatômica. MÉTODOS: Estudo comparativo, descritivo e analítico, de corte transversal. O grupo de casos foi formado por 31 indivíduos portadores de DMRI com idade entre 51 e 88 anos. O grupo de controles ficou composto por 31 indivíduos considerados "sadios", não portadores de DMRI com idade entre 61 e 80 anos. Os grupos foram pareados por sexo e idade. Realizou-se a perimetria macular estática, vermelho-vermelho, com o oftalmoscópio de rastreamento a laser (ORL. Os resultados da perimetria macular foram correlacionados à lesão anatômica identificada no local correspondente pelo laser infravermelho e fotografias coloridas. RESULTADOS: As áreas com neovasos ou atrofia apresentaram sensibilidade significantemente diferente em relação às áreas com ausência de lesões anatômicas nos pacientes com DMRI. Houve perda funcional significativa em áreas com ausência de lesões anatômicas nos pacientes com DMRI em relação ao grupo de controles. CONCLUSÕES: Áreas com neovasos ou atrofia podem ser fatores individuais de piora da sensibilidade macular localizada. Pode ocorrer perda funcional mesmo sem lesão anatômica aparente nos pacientes com DMRI.PURPOSES: To evaluate the correlation between anatomical changes (hard druses, soft druses, hyperpigmentation, new vessels, detachment of retinal pigment epithelium, hypopigmentation and chorioretinal atrophy and light sensitivity in patients with age-related macular

  10. A single-arm, investigator-initiated study of the efficacy, safety, and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration previously treated with ranibizumab or bevacizumab (ASSESS study: 12-month analysis

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    Singh RP

    2015-09-01

    Full Text Available Rishi P Singh, Sunil K Srivastava, Justis P Ehlers, Fabiana Q Silva, Rumneek Bedi, Andrew P Schachat, Peter K Kaiser Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA Summary statement: In subjects with active exudative age-related macular degeneration, treating with a fixed intravitreal aflibercept injection dosing regimen for 12 months demonstrated improved anatomic and vision endpoints from baseline.Purpose: Switching therapies in neovascular age-related macular degeneration (AMD may offer an advantage for some patients. This study evaluates the efficacy of intravitreal aflibercept injection (IAI in subjects previously treated with ranibizumab and/or bevacizumab.Methods: Subjects (n=26 were given monthly 2 mg of IAI for 3 months, followed by 2 mg once in every 2 months for up to 12 months. The mean absolute change from baseline in central subfield thickness (CST measured by optical coherence tomography and the mean change from baseline in best-corrected visual acuity (BCVA early treatment in diabetic retinopathy study (ETDRS letter score were obtained. Additionally, the percentage of subjects who gained or lost ≥15 letters of vision and the percentage of subjects who are 20/40 or better or 20/200 or worse were evaluated.Results: There was a mean decrease in CST of -50.3  µm (P<0.001 and a mean increase in ETDRS BCVA of +9.2 letters (P<0.001. Twenty-seven percent of subjects experienced a  ≥15-letter improvement in visual acuity, and no subject lost ≥3 lines of vision from baseline. Fifty percent of subjects were 20/40 or better, and 11.5% of subjects were 20/200 or worse at month 12.Conclusion: Fixed IAI dosing regimen for 12 months demonstrated improved anatomic and vision endpoints in subjects with active exudative AMD. Keywords: aflibercept, age-related macular degeneration, bevacizumab, ranibizumab, vascular endothelial growth factors

  11. Macular Degeneration - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Macular Degeneration URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Macular Degeneration - Multiple Languages To use the sharing features on ...

  12. CCR3在湿性年龄相关性黄斑变性中的研究进展%Study progress of CCR3 in wet age -related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    吴宪巍; 刘哲丽

    2014-01-01

    研究显示,趋化因子受体3(chemokine receptor 3,CCR3)在眼部主要分布于视网膜色素上皮细胞中,亦表达于脉络膜血管内皮细胞( CECs )中。 CCR3的特异性高表达在湿性年龄相关性黄斑变性( age -related macular degeneration ,AMD)中被发现,并被证明在湿性AMD患者脉络膜新生血管( choroidal neovascularization ,CNV)的产生中具有重要作用。本文拟对CCR3的结构、功能、目前研究存在的问题及未来的研究方向做一综述。相信随着对CCR3研究的进一步深入,必将帮助我们寻找到一种湿性AMD诊断和治疗的新方法,同时也可能对其它CNV性疾病研究以及新的抗CNV药物提供重要参考。%According to the study, chemokine receptor 3 ( CCR3 ) in the eye is mainly distributed in retinal pigment epithelial cells, and also expressed in the choroidal vascular endothelial cells ( CECs ) . The specificity of CCR3's high expression in wet age -related macular degeneration ( AMD) was found, and it is proved that in wet-AMD patients, it plays an important role in the formation of choroidal neovascularization ( CNV) .In this paper, the structure, function, the problem of current research and the future direction of CCR3 were summarized.It is believed that with the further research on CCR3, it will not only help us to find a new method of wet-AMD diagnosis and treatment, but also may provide an important reference for other CNV disease research and new anti-CNV drugs.

  13. Reliability and reproducibility of spectral and time domain optical coherence tomography images before and after correction for patients with age-related macular degeneration [v2; ref status: indexed, http://f1000r.es/50m

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    Mohammad A. Sadiq

    2015-03-01

    Full Text Available Purpose: To evaluate the reproducibility and reliability of optical coherence tomography scans obtained using the time domain (TD-OCT StratusTM OCT, and the Spectral Domain (SD-OCT SpectralisTM and CirrusTM OCT devices before and after manual correction in eyes with either Neovascular (NV-AMD or Non-Neovascular (NNV-AMD age-related macular degeneration. Design: Prospective observational study. Methods: Setting: University-based retina practice. Patients: Thirty-six patients (50 eyes with NV-AMD or NNV-AMD. Procedure: OCT scans were taken simultaneously using one TD-OCT and two SD-OCT devices. Main Outcome Measures: Macular thickness measurements were assessed before and after correction of the algorithm by constructing Bland-Altman plots for agreement and calculating intraclass correlation coefficients (ICCs and coefficients of repeatability (COR to evaluate intraclass repeatability. Results: Spectralis had the highest number of images needing manual correction.  All machines had high ICCs, with Spectralis having the highest.  Also, Bland-Altman plots indicated that there was low agreement between Cirrus™ and Stratus™, Spectralis™ and Stratus™, while there was good agreement between the Cirrus™ and Spectralis™.  The CORs were lowest for SpectralisTM and similar and higher for CirrusTM and StratusTM.  Agreement, CORs, and ICCs generally improved after manual correction, but only minimally.  Conclusion: Agreement is low between devices, except between both SD-OCT machines.  Manual correction tends to improve results.

  14. Association of the polymorphism Y402H in the CFH gene with response to anti-VEGF treatment in age-related macular degeneration: a systematic review and meta-analysis.

    Science.gov (United States)

    Hong, Nan; Shen, Ye; Yu, Chen-Ying; Wang, Shu-Qun; Tong, Jian-Ping

    2016-06-01

    To explore whether the complement factor H (CFH) polymorphism rs1061170/Y402H is associated with responsiveness to antivascular endothelial growth factor (VEGF) agents in age-related macular degeneration (AMD). We reviewed the English literature to examine the association between the polymorphism rs1061170/Y402H of the CFH gene and responsiveness to treatment with anti-VEGF drugs in AMD patients. A meta-analysis of eligible studies was also performed. Pooled odds ratios (ORs) and 95% CIs were estimated using Stata V.12.0. Statistical heterogeneity was measured using Q-statistic testing. Fourteen relevant studies including a total of 2963 AMD patients were eligible. In AMD patients without a treatment history, individuals carrying the rs1061170/Y402H TT genotype were more likely to achieve a better outcome (OR = 1.932, 95% CI = 1.125-3.317, p = 0.017) than those carrying the CC genotype. The polymorphism rs1061170/Y402H might be a genetic predictor of treatment response to anti-VEGF therapy in AMD patients. Further prospective research including a larger number of patients is needed to validate this finding. PMID:27151934

  15. Functional single nucleotide polymorphism in IL-17A 3' untranslated region is targeted by miR-4480 in vitro and may be associated with age-related macular degeneration.

    Science.gov (United States)

    Popp, Nicholas A; Yu, Dianke; Green, Bridgett; Chew, Emily Y; Ning, Baitang; Chan, Chi-Chao; Tuo, Jingsheng

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. Genetic factors contributing to AMD include single nucleotide polymorphisms (SNPs) in immune-related genes including CFH, C2, CFI, C9, and C3, thus implicating these pathways in AMD pathogenesis. MicroRNAs (miRNAs) are powerful regulators of gene expression and execute this function by binding to the 3' untranslated region (3'UTR) of target mRNAs, leading to mRNA degradation. In this study, we searched for the possible association of SNPs in the 3'UTR region of IL-17A, a gene implicated in AMD pathogenesis without any previous SNP association with AMD. Using two independent sample cohorts of Caucasian subjects, six SNPs in the IL-17A 3'-UTR were selected for genotyping based on bioinformatic predictions of the SNP effect on microRNA binding. The SNP rs7747909 was found to be associated with AMD (P < 0.05) in the NEI cohort, using a dominant model logistic regression. Luciferase reporter gene assays and RNA electrophoretic mobility shift assays were performed using ARPE-19 cells to confirm the preferential binding of microRNAs to the major allele of the SNP. Our findings support the hypothesis that microRNA-mediated gene dysregulation may play a role in the pathogenesis of AMD. PMID:26765636

  16. CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study.

    Directory of Open Access Journals (Sweden)

    Bénédicte M J Merle

    Full Text Available Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD. We investigated whether genotype could influence response to docosahexaenoic acid (DHA-supplementation in the occurrence of choroidal new vessels (CNV.The Nutritional AMD Treatment 2 (NAT2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo.Patients carrying the risk allele (C for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR=0.97; 95% Confidence Interval (CI: 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous. Patients carrying the risk allele (T for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12 for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous. A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01. We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008.These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation.ISRCTN registry 98246501.

  17. Radiotherapy in age-related macula degeneration

    International Nuclear Information System (INIS)

    Purpose: To ascertain the benefit from radiotherapy in age-related macula degeneration in a single-arm longitudinal study. Methods and Materials: From 1997 to 1998, 39 patients with occult and 33 patients with classic choroidal neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and measurements of visual acuity were performed before and 3, 6, and 12 months after irradiation. Results: Complete follow-up data for 1 year were available from 69 patients. The mean patient age was 72 years (range 49-92). Vision decreased in 43, was stable in 18, and improved in 8 cases. The mean vision deteriorated significantly (p=0.02, Wilcoxon test), particularly within the first 3 months. Patients with occult CNV did significantly better than did those with classic CNV (p=0.03). The proportion of patients retaining vision ≥0.2 fell from 65% to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV from 77% to 56% (p<0.02), respectively. CNV size increased in 30 patients and was stable in 38. Neither age (p=0.17) nor gender (p=0.21, chi-square test) influenced prognosis. Four patients reported transitional complaints. Conclusion: Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision and reading ability were not preserved in most patients

  18. Long-term (60-month results for the implantable miniature telescope: efficacy and safety outcomes stratified by age in patients with end-stage age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Boyer D

    2015-06-01

    Full Text Available David Boyer,1 K Bailey Freund,2 Carl Regillo,3 Marc H Levy,4 Sumit Garg5 1Retina-Vitreous Associates Medical Group, Beverly Hills, CA, 2Vitreous-Retina-Macula Consultants of New York, New York, NY; 3Wills Eye Institute, Philadelphia, PA, 4Sarasota Retina Institute, Sarasota, FL, 5The Gavin Herbert Eye Institute (University of California, Irvine Irvine, CA, USA Background: The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT in patients with bilateral, end-stage, age-related macular degeneration (AMD.Methods: A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years with AMD and moderate-to-profound bilateral central visual acuity loss (20/80–20/800 resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to <75 years [group 1; n=70] and patient age ≥75 years [group 2; n=127], with a comparative evaluation of change in best-corrected distance visual acuity (BCDVA, quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD. Follow-up in an extension study was 60 months.Results: Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41±2.69 lines in all patients (n=76, with 2.64±2.55 lines in group 1 and 2.09±2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis >30 days after surgery (7/70; 10% and persistent corneal edema (3/70; 4.3%; and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%, corneal edema >30 days after surgery (9/127; 7.1%, and persistent corneal edema (6/127; 4.7%. Significant

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

    Science.gov (United States)

    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. PMID:27256991

  20. The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease

    Science.gov (United States)

    Taylor, J; Scott, L J; Rogers, C A; Muldrew, A; O'Reilly, D; Wordsworth, S; Mills, N; Hogg, R; Violato, M; Harding, S P; Peto, T; Townsend, D; Chakravarthy, U; Reeves, B C

    2016-01-01

    Introduction Standard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions. Methods The Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group. The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists. Discussion This trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial. PMID:26449197

  1. What Is Age-Related Macular Degeneration?

    Science.gov (United States)

    ... Uveitis Focus On Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center ... Uveitis Focus On Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center ...

  2. Facts about Age-Related Macular Degeneration

    Science.gov (United States)

    ... changes can lead to feelings of loss, lowered self-esteem, isolation, and depression. In addition to getting medical ... natural process. Lend support by “being there.” What research is being done? NEI conducts and supports research ...

  3. 老年黄斑变性高危患者预防性治疗的临床应用%Clinical Application of Prophylactic Treatment for High Risk Patients With Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    张云贵

    2015-01-01

    Objective Research on the clinical preventive treatment for elderly patients at high risk of macular degeneration. To reduce the incidence of patients with the disease. Methods Chose 120 cases of macular degeneration in elderly high-risk patients in our hospital to carry out research and analysis,we used prophylactic treatment of patients with anti-aging drugs and medication adjustments microcirculation. Results 80% patients maintained the status quo or improved,10% patients with symptoms of vision loss,5% patients with macular degeneration,5% not able to adhere to the completion of treatment,and had vision loss. Conclusion High risk patients of macular degeneration using anti-aging,adjust the microcirculation,nutrients and other treatment,the patient's vision can be greatly improved,reducing the chance of macular degeneration,the patient's quality of life is guaranteed.%目的:对老年黄斑变性高危患者的临床预防性治疗进行研究分析,探讨其作用,为降低患者该疾病的发生率,预防失明提供参考。方法选取我院的120例黄斑变性高危老年患者来进行研究分析,使用预防性治疗,对患者提供抗衰老药物和调整微循环药物,对患者的治疗情况进行研究分析。结果全部患者有80%其视力能够维持现状或者有所改善,有10%患者出现了视力衰退的症状,5%患者有黄斑变性,5%不能够坚持完成治疗,视力衰退。结论黄斑变性高危患者使用抗衰老、调整微循环、营养素等治疗,可以让患者的视力得到较大的改善,黄斑变性几率降低,患者的生活品质有所保障。

  4. Avaliação da função macular por eletrorretinografia focal e por angiofluoresceinografia em pacientes com degeneração macular relacionada à idade neovascular submetidos à terapia fotodinâmica com verteporfina Evaluation of the macular function by focal electroretinography and by fluorescein angiography in patients with neovascular age-related macular degeneration submitted to verteporfin photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Akiyoshi Oshima

    2009-02-01

    Full Text Available OBJETIVOS: Avaliar a função macular por eletrorretinografia focal e angiofluoresceinografia em pacientes com degeneração macular relacionada à idade neovascular submetidos à terapia fotodinâmica com verteporfina. MÉTODOS: Estudo prospectivo incluindo 22 pacientes (12 homens com degeneração macular relacionada à idade e lesão neovascular coroídea subfoveal predominantemente clássica, não consecutivos, tratados com terapia fotodinâmica com verteporfina padrão e acompanhados por um período de 12 meses. A acuidade visual melhor corrigida foi medida utilizando tabela ETDRS, as alterações das lesões foram avaliadas pela angiofluoresceinografia e a função dos cones foram obtidas pela eletrorretinografia focal na visita inicial e nas subsequentes a cada três meses. RESULTADOS: Todos os pacientes completaram as visitas programadas. Após uma média de 3,5 sessões por paciente, a variação da acuidade visual melhor corrigida não foi significante no decorrer do estudo. Em 50% dos pacientes a variação da acuidade visual melhor corrigida foi >1 linha. Ao final do estudo observou-se ausência de vazamento em 86% dos pacientes. A média da amplitude e latência do ERG focal na visita inicial foram de, respectivamente, 194,88 nV e 29,19 ms e as variações no decorrer do estudo não foram significantes. CONCLUSÕES: Não foram encontradas diferenças na amplitude e latência do eletrorretinografia focal após um período de 9 meses. A acuidade visual melhor corrigida não sofreu variações significativas ao longo dos 12 meses. A lesão foi significativamente reduzida ao longo do tempo e houve uma correlação negativa entre a amplitude e a acuidade visual melhor corrigida.PURPOSE: To evaluate macular function by focal electroretinography and fluorescein angiography (FA in patients with neovascular age-related macular degeneration submitted to verteporfin photodynamic therapy (VPT. METHODS: Prospective study involving 22 patients

  5. Role of long-chain and very-long-chain polyunsaturated fatty acids in macular degenerations and dystrophies

    OpenAIRE

    Liu, Aihua; Lin, Yanhua; Terry, Ryan; Nelson, Kelly; Bernstein, Paul S.

    2011-01-01

    Macular degeneration is a progressive, bilateral eye disorder that damages the macula of the human eye. The most common form of macular degeneration is age-related macular degeneration (AMD), which is the leading cause of irreversible blindness in people older than 50 years in developed countries. Autosomal dominant Stargardt disease-3 (STGD3) is an inherited macular dystrophy that has clinical features similar to dry AMD, but occurs at a much earlier age. It is caused by a mutation in the el...

  6. microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration.

    Directory of Open Access Journals (Sweden)

    Surjyadipta Bhattacharjee

    Full Text Available The aggregation of Aβ42-peptides and the formation of drusen in age-related macular degeneration (AMD are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Aβ42-peptides from the extracellular space. The triggering receptor expressed in myeloid/microglial cells-2 (TREM2, a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical component of Aβ42-peptide clearance. Here we report a significant deficit in TREM2 in AMD retina and in cytokine- or oxidatively-stressed microglial (MG cells. RT-PCR, miRNA-array, LED-Northern and Western blot studies indicated up-regulation of a microglial-enriched NF-кB-sensitive miRNA-34a coupled to a down-regulation of TREM2 in the same samples. Bioinformatics/transfection-luciferase reporter assays indicated that miRNA-34a targets the 299 nucleotide TREM2-mRNA-3'UTR, resulting in TREM2 down-regulation. C8B4-microglial cells challenged with Aβ42 were able to phagocytose these peptides, while miRNA-34a down-regulated both TREM2 and the ability of microglial-cells to phagocytose. Treatment of TNFα-stressed MG cells with phenyl-butyl nitrone (PBN, caffeic-acid phenethyl ester (CAPE, the NF-kB - [corrected] inhibitor/resveratrol analog CAY10512 or curcumin abrogated these responses. Incubation of anti-miRNA-34a (AM-34a normalized miRNA-34a abundance and restored TREM2 back to homeostatic levels. These data support five novel observations: (i that a ROS- and NF-kB - [corrected] sensitive, miRNA-34a-mediated modulation of TREM2 may in part regulate the phagocytic response; (ii that gene products encoded on two different chromosomes (miRNA-34a at chr1q36.22 and TREM2 at chr6p21.1 orchestrate a phagocytic-Aβ42-peptide clearance-system; (iii that this NF-kB-mediated-miRNA-34a-TREM2 mechanism is inducible from outside of the cell; (iv that when operating normally, this pathway can clear Aβ42 peptide monomers from the

  7. Intravitreal bevacizumab and cataract surgery after wet age-related macular degeneration%玻璃体腔内注射Bevacizumab联合白内障手术治疗湿性年龄相关性黄斑变性

    Institute of Scientific and Technical Information of China (English)

    José M Ruiz-Moreno; Javier A Montero; Pedro Amat-Peral; Francisco L Lugo

    2010-01-01

    目的:探讨玻璃体腔内注射bevacizumab (Avastin) 联合白内障手术预防脉络膜新生血管(choroidal neovascularization,CNV)的再次激活及年龄相关性黄斑变性(age-related macular degeneration, AMD).方法:对12例接受湿性年龄相关变性治疗的白内障患者给予透明角膜切口白内障超声乳化和人工晶状体植入手术,最后予以玻璃体腔内注射1.25mg bevacizumab (0.05mL).主要评价指标:视力恢复、脉络膜新生血管的再次激活,及相干光断层成相术(OCT)对渗漏液体的评估.结果:患者最佳矫正视力(best-corrected visual acuity, BCVA)术后显著提高(脉络膜新生血管闭合后P<0.01,白内障发生后P=0.049,t检验).白内障术后平均随访时间为11.8mo(标准差6.1,范围3~22mo),随访期内患者未出现脉络膜新生血管的再次激活及新的脉络膜新生血管病变.结论:在给予脉络膜新生血管及年龄相关性黄斑变性治疗的患者,白内障手术联合玻璃体腔内注射bevacizumab可预防脉络膜新生血管的再次激活.

  8. Complicações na facoemulsificação interferem no aparecimento da degeneração macular relacionada à idade? Does phacoemulsification complications interfere in the appearance of age related macular degeneration?

    OpenAIRE

    Angela Bettarello; Wagner Ghirelli; Tadeu Cvintal

    2007-01-01

    OBJETIVO: Avaliar se uma cirurgia de catarata por facoemulsificação com complicação intra-operatória é um fator de risco para o desenvolvimento de degeneração macular relacionada à idade. MÉTODOS: Estudo retrospectivo longitudinal tipo caso-controle com revisão dos prontuários de 1150 pacientes submetidos à facectomia no período de 1995 a 1999, realizadas por apenas um cirurgião (T.C.). Para cálculo estatístico foram utilizados o Qui-quadrado com correção de Yates, Teste Exato de Fisher e Tes...

  9. Low-dose fractionated percutaneous teletherapy in age-related macular degeneration with subfoveolar neovascularization - 3 year results; 3 Jahre Erfahrung mit der niedrig dosierten fraktionierten perkutanen Teletherapie bei subfoveolaeren Neovaskularisationen. Klinische Ergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Schittkowski, M.; Schneider, H.; Guthoff, R. [Universitaetsaugenklinik Rostock (Germany); Grueschow, K.; Ziegler, P.G.; Fietkau, R. [Zentrum fuer Radiologie, Univ. Rostock (Germany)

    2001-07-01

    The effect of low dose fractionated percutaneous teletherapy to visual acuity and the changes in subfoveolar neovascular membranes in age-related macular degeneration were investigated. Patients and Method: 126 eyes of 118 patients (age 55-89 years; mean 74 ys.) were treated. Best distal and near visual acuity was assessed prior to (= initial visual acuity [IVA]) and 3, 6, 12, 18, 24, and 36 months after teletherapy. Fluorescein angiography was performed prior to and 6, 12, 24 and 36 months after radiation therapy. For analysis patients were divided into different groups by IVA and membrane size. Maximal duration of observation was 36 months. Teletherapy was done by a 9-MeV photon linear accelerator through a lateral port in half-beam technique with a single dose of 2 Gy up to a total dose of 20 Gy within 12 days. Results: No severe negative side effects have been observed. Eight patients reported of epiphora and four patients complained of transient sicca syndrome. Visual acuity decreased more than one line in the group IVA 0.05-0.2. The group IVA 0.3-0.5 remained unchanged for 1 year. We found a tendency for increased visual acuity in group IVA {>=} 0.6 for 18 months. After that time both groups showed decreased visual acuity, but all these patients reported of reduced metamorphopsia and increased color and contrast perception. Conclusions: There is an influence of low dose fractionated percutaneous teletherapy on visual acuity, subfoveal neovascular membranes and metamorphopsia. IVA and duration of anamnesis play an important role. There seems to be no persistent effect; possibly increased dosage will bring a benefit. (orig.) [German] Es wurde die Wirkung der Bestrahlung auf die Sehschaerfe bei altersabhaengiger Makuladegeneration mit chorioidalen Neovaskularisationen, die nach den MPS-Kriterien einer Laserkoagulation nicht zugaenglich sind, untersucht. Patienten und Methode: 126 Augen von 118 Patienten im Alter von 55-89 Jahren (Mittel 74) wurden behandelt. Ein

  10. Epidemiological factors associated with exudative age-related macular degeneration in Spain%西班牙渗出性老年性黄斑变性的相关流行病学因素

    Institute of Scientific and Technical Information of China (English)

    Javier A Montero; Hortensia S(a)nchez-Tocino; Maria Josefa Mart(i) Maldonado; Concepci(o)n Arnaiz Ni(n)o; Rosa Maria P(e)rez Bartolom; Antonio Valera Coomonte

    2008-01-01

    AIM: To report the demographic characteristics of a sample of population affected by exudative age-related macular degeneration (AMD) in the region of Castilla-Leon (North-Central Spain), and to compare them with a group of population of the same age and from the same geographic area.METHODS: In this observational, prospective study, AMD patients attending a regional reference clinic for photodynamic therapy were interviewed. The patients reported their medical history for high blood pressure, hyperlipemia and smoking habit. Iris color was examined and classified as fight (green, blue and grey) or dark (hazel, brown, black).RESULTS: A total of 343 patients were interviewed. Mean age at onset was 74.9 years (range 55 to 93), Among whom 64.5% were female and 35.5% male. Iris color was rated as light in 45.1% of the patients. Arterial hypertension (AH) was present in 50% of the cases and 15.3% were on treatment for hypercholesterolemia, and 30.2% of the patients were smokers or had quit smoking (80.9% of males).CONCLUSION: The frequency of light colored iris is higher among patients with exudative AMD. In our series, other risk factors for exudative AMD were smoking habit in males, not being on treatment for hypercholesterolemia and being female.%目的:报告在西班牙Castilla-Leo地区患有渗出性老年性黄斑变性(AMD)的样本人群的流行病学特点,并与一组来自同一地区和相同年龄人群进行比较.方法:在本次观察性前瞻性调查中,我们访问了在一家地区性诊所接受光动力学疗法的AMD患者.患者报告了高血压、高血脂、吸烟的病史,检查患者虹膜颜色并分为浅色(绿色、蓝色、灰色)和深色(淡褐色、褐色、黑色).结果:共有343名患者接受了访问,平均年龄为74.9岁(55~93岁),其中64.5%为女性,35.5%为男性,有45.1%的患者虹膜颜色被划为浅色.这些患者中,有50%有动脉性高血压,15.3%接受高胆固醇血症治疗,30.2%吸烟

  11. 上海市北新泾街道老年人年龄相关性黄斑变性的患病率调查%Prevalence of age-related macular degeneration in Beixinjing Community of Shanghai

    Institute of Scientific and Technical Information of China (English)

    黄晓波; 邹海东; 王宁; 王伟伟; 傅炯; 沈彬杰; 许迅; 张皙

    2012-01-01

    Objective To investigate the prevalence of age-related macular degeneration (AMD) in residents aged ≧60 years in Beixinjing Community of Shanghai. Methods The prevalence and related factors of AMD in residents aged ≧60 years in Beixinjing Community of Shanghai were investigated between November 2007 and April 2008 with cluster sampling. An interview concerning general data, history of diagnosis and treatment of eye diseases, daily living visual acuity and corrected visual acuity was carried out. Basic eye examination was performed, and 2 photographs covering 45° of posterior eye fundus area were acquired in each eye with fundus camera. The diagnosis of AMD was made by two or moreophthalmologists, and the classification of AMD was based on the criteria from Chinese Eye fundus Diseases Group. Results A total of 4 153 residents were included, and 3 571 finished examinations, with the examination rate of 85. 99% . Four hundred and seventy-seven patients (778 eyes) were diagnosed as AMD, accounting for 13.36% of the residents finishing examinations. Sixty-four patients (85 eyes) were diagnosed as exudative AMD, occupying 1.79% of the residents finishing examinations. The prevalences of AMD in the age groups of 60 - 69, 70 - 79 and no less than 80 were 6. 23% , 14. 98% , and 29. 91% , respectively, with significant differences ( χ2 =169. 40, P 0. 05) . In eyes of AMD, 3. 08% and 18. 51% were identified as blind or low vision. In eyes of exudative AMD, 15. 29% and 32. 95% were identified as blind or low vision, which were higher than those in eyes of atrophic AMD ( 1. 59% and 16. 73%) . Conclusion The prevalence of AMD increases with age, and decreases with education level. AMD may lead to severe visual acuity impairment.%目的 调查上海市北新泾街道≥60岁人群中年龄相关性黄斑变性( AMD)的患病情况.方法 于2007年11月-2008年4月,采用整群抽样的方法对上海市北新泾街道≥60岁的居民进行AMD患病率和相关因素的

  12. Radiation treatment of subfoveal exsudative macular degeneration

    International Nuclear Information System (INIS)

    Treatment of patients with neovascular age-related macular degeneration (AMD) presenting with CNV which extend under the center of the fovea is discouraging. A new therapeutic regimen is the application of radiation, but the results of initial studies are contradictory. In a prospective study 40 patients - 9 males and 31 females - with a mean age of 74 years and exsudative AMD with involvement of the fovea were treated with radiation. Eight patients had classic, well-defined CNV, 32 had occult lesions. Radiation was administered on the posterior pole with a 8 MV-photon beam at a linear accelerator. A dose of 14.4 Gy, 1.8 Gy per day, 5 fractions per week was delivered through a single lateral port. After a follow-up of one year the visual acuity was stable in 6 patients and deteriorated by two or more lines in 34 patients. The central visual fields decreased significantly from 16.5 dB to 12.4 dB. The neovascular changes progressed in all patients. Our results did not show a beneficial effect of the radiation treatment with a dosage of 14.4 Gy whether on visual acuity nor on exsudative changes in patients with AMD. (author)

  13. Microbiota bacteriana da conjuntiva no pré-operatório de injeção intravítrea de antiangiogênico por degeneração macular relacionada à idade comparada com a de cirurgia de catarata Preoperative conjunctival bacterial microbiota of antiangiogenic intravitreous injection for age-related macular degeneration compared to cataract surgery preoperative microbiota

    Directory of Open Access Journals (Sweden)

    José Ricardo Diniz

    2010-06-01

    pacientes no pré-operatório de cirurgia de catarata.Purpose: To evaluate the conjunctival bacterial microbiota and antibiogram profile in the preoperative of antiangiogenic intravitreous injection for age-related macular degeneration, and compare to the preoperative microbiota of patients submitted to cataract surgery. Methods: Cross-sectional, observational, case series study. Two groups were organized: group I (macular degeneration with 26 eyes from 26 patients (12 men/14 women with mean age of 69.2 ± 11.5 years; group II (cataract with 27 eyes from 27 patients (9 men/18 women with mean age of 67.6 ± 7.9 years. The groups were similar regarding age (p=0.538 and gender (p=0.787. The lower conjunctival sac was swabbed and the obtained material was immediately put in a tube filled with liquid culture media BHI ("brain heart infusion". Samples were processed according to standard laboratory techniques and antibiogram was determined for each bacterial colony. Results: Twenty-six bacterial colonies growth in group I, with 2 eyes showing no growth and 30 colonies growth in group II. Gram positive bacteria were more prevalent in both groups: 23/26 colonies (88.4% in group I and 29/30 colonies (96.7% in group II, with a Staphylococcus aureus predominance in both groups, with 16 samples (61.5% and 17 (56.7%, respectively. Coagulase negative Staphylococcus was the second most common identified bacteria, with 19.2% in group I and 20.0% in group II. No differences between the groups reached statistical significance. No statistically significant difference was noted on the antibiotic sensibility between both groups. Conclusions: There was no difference in the distribution of bacteria and antibiogram profile of the conjunctival microbiota in the preoperative of intravitreous injection of antiangiogenic for macular degeneration compared to the preoperative of cataract surgery.

  14. Apolipoprotein E allele-dependent pathogenesis: A model for age-related retinal degeneration

    OpenAIRE

    Malek, G; Johnson, L V; Mace, B E; Saloupis, P.; Schmechel, D E; Rickman, D. W.; Toth, C. A.; Sullivan, P. M.; Rickman, C. Bowes

    2005-01-01

    Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known AMD risk factors: advanced age, high fat cholesterol-rich (HF-C) diet, and apolipoprotein E (apoE) genotype. Eyes of aged, targeted replacement mice expressing human apoE2, apoE3, or apoE4 and maintained on a HF-C diet show apoE isoform-dep...

  15. The morphometric peculiarities of the eyes with tractional macular edema after age-related cataract phacoemulsification

    OpenAIRE

    V.A. Rudenko; E. L. Sorokin; Egorov, V. V.

    2013-01-01

    ABSTRACT Purpose. To study the morphometric peculiarities of eyes with tractional macular edema after phacoemulsification of age-related cataract. Material and methods. There were examined 72 patients (72 eyes) with macular edema (ME) developed after phacoemulsification of age-related cataract. The control group included 72 eyes of 72 patients without ME after phacoemulsification for age-related cataract in the follow-up of 1.5-2 years. The measurement of the axial length and h...

  16. Intravitreal Ranibizumab Therapy in Wet Type Macular Degeneration

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    Hüseyin Dündar

    2014-10-01

    Full Text Available Objectives: To evaluate the efficacy and safety of intravitreal ranibizumab treatment in all types of choroidal neovascularization that developed secondary to age-related macular degeneration. Materials and Methods: We enrolled ninety-four eyes of 92 patients with previously untreated neovascular age-related macular degeneration who underwent intravitreal ranibizumab injection and were followed for at least 12 months. All of the patients underwent a complete examination, including best-corrected visual acuity (BCVA (Snellen, biomicroscopy, and dilated fundus examination at preoperatively and postoperative follow-up visits. Number of injections and frequency of follow-up visits per year were evaluated. Size, location, and type of the lesions were evaluated by fluorescein angiography (FA. Pre- and postoperative changes in lesion size, central macular and foveal thickness measured by OCT were compared. Results: A total of 92 patients (36 women and 56 men with a mean age of 69.1±11.0 years were evaluated. Mean follow-up time was 14.6±3.44 (12-25 months, and mean number of injections was 4.9±1.81 (3-12. The average annual number of follow-up visits was 9.2±1.02 (8-12. Patients’ mean best-corrected visual acuity increased by 12.1 letters. The lesion size was 3.27±0.95 µm at pre-treatment period and improved to 2.72±1.15 µm in post-treatment period measured by FA (p=0.006. Leakage was still detected in ten patients at final follow-up visit. Statistically significant decrease in macular and foveal thickness was recorded in all post-treatment measurements compared to pre-treatment ones. Conclusion: Intravitreal ranibizumab treatment is efficient and safe in all types of choroidal neovascularization that develops secondary to age-related macular degeneration. Flexible dosing interval increases the patient compliance and anatomical and functional success rate. (Turk J Ophthalmol 2014; 44: 356-60

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

    Science.gov (United States)

    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). PMID:22702721

  18. Avaliação da tomografia de coerência óptica em pacientes portadores de degeneração macular relacionada à idade tratada com terapia fotodinâmica com verteporfina Ocular coherence tomography in age-related macular degeneration patients treated with photodynamic therapy with vertepofirin

    Directory of Open Access Journals (Sweden)

    Arnaldo Furman Bordon

    2008-12-01

    mensuradas não tiveram variação estatisticamente significante. A depressão foveal estava presente em 36,4% dos olhos na visita inicial e em 78,3% em V12. O fluido sub-retiniano estava presente em 36,4% em V0 e em 8,7% em V12. A AV na visita inicial foi 0,93 e na visita final foi 1,04 (p = 0,127. CONCLUSÕES: A AV permaneceu inalterada ao longo do estudo. A depressão foveal estava presente em 78,3% dos olhos em V12. A diminuição da FIRT e da TFT foi estatisticamente significante entre V0 e V12.PURPOSE: To identify the optical coherence tomography (OCT findings in patients with age-related macular degeneration (ARMD treated with photodynamic therapy (PDT. STUDY DESIGN: Open, non-randomized, interventional case series. METHODS: ARMD patients were submitted to a complete ophthalmological examination, fluorescein angiography, and OCT at baseline (V0, 3, 6, 9 and 12 months (V3, V6, V9 and V12, respectively. PDT was carried out according to the TAP study. Visual acuity (VA was measured using the logMAR ETDRS chart. The following foveal measurements were performed: foveal intraretinal thickness (FIRT, foveal choriocapillaris - RPE complex thickness (FCC-RPET and total foveal thickness (TFT. The extrafoveal thicknesses measured were: extrafoveal intraretinal thickness (EFIRT, extrafoveal choriocapillaris - RPE complex thickness (EFCC-RPET and total extrafoveal thickness (TEFT. Statistical analysis was performed using the block variance analysis test. RESULTS: Twenty-three eyes of 23 patients were enrolled. This study identified nine OCT patterns: 1 thickening of the foveal intraretinal layers; 2 thickening of the extrafoveal intraretinal layers; 3 thickening of the foveal choriocapillaris - RPE complex; 4 thickening of the extrafoveal choriocapillaris - RPE complex; 5 intraretinal fluid; 6 subretinal fluid; 7 subretinal pigment epithelium (RPE fluid; 8 vitreo-retinal adhesion; 9 foveal depression. At baseline, FIRT and TFT were 398.5 µ and 639.2 µ, respectively. At V12 they

  19. Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

    Science.gov (United States)

    GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

    2014-01-01

    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

  20. External radiotherapy in macular degeneration: technique and preliminary subjective response

    International Nuclear Information System (INIS)

    Purpose: This study attempted to assess the toxicity and possible preliminary benefits from the administration of low-dose external beam irradiation for age-related macular degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neovasculature which would result in reabsorption of fluid and blood. This would reduce the risk for further leakage or bleeding, as well as subretinal fibrosis. Consequently, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet ARMD with the possibility for slight improvement. Methods and Materials: Allegheny University Department of Radiation Oncology treated 41 patients prospectively from January through October 1995 with low-dose irradiation for wet-type macular degeneration. A total of 39 patients were treated with a total dose of 14.4 Gy in eight fractions of 1.8 Gy/fraction over 10-13 elapsed days. The first two patients were treated with a total dose of 10 Gy in fivefractions of 2 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. Some of the patients (36.7%) had laser treatments in the study eye: 21.9% (9) once, 5% (2) twice, 9.7% (4) thrice or more. Subjective visual acuity and toxicity data were collected on all patients. Results: At 2-3 weeks after treatment 29 patients (70%) retained their visual acuity without change, 10 (24.5%) stated they had improved vision, and 2 (4.8%) stated their vision continued to decrease. At 2-3 months after treatment, 27 patients (65.8%) had no change in their vision, 11 (27%) had an improvement in their vision, and 3 (7.2%) had a decrease in visual acuity. Six patients of 41 in the treated group had acute transient side effects. Conclusion: Our observations in this group of 41 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age-related wet-type macular degeneration

  1. Radiation therapy for macular degeneration: technical considerations and preliminary results

    International Nuclear Information System (INIS)

    Purpose: This study was undertaken to assess the toxicity and possible benefits from the administration of low-dose external-beam irradiation for Age-Related Macular Degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neo-vasculature, resulting in reabsorption of fluid and blood thus reducing the risk for further leakage or bleeding, as well as subretinal fibrosis. Clinically, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet type of ARMD with the possibility for some visual improvement. Methods and Materials: Allegheny University Hospitals, Hahnemann, Department of Radiation Oncology, treated 278 patients prospectively beginning in January 1995 with low-dose irradiation for wet-type macular degeneration. Two hundred forty-nine patients were treated with a total dose of 14.40 Gy in eight fractions of 1.80 Gy over 10-13 elapsed days, and 27 patients with 20 Gy at 2 Gy per fraction over 12-15 days. The first two patients were treated to a total dose of 10.00 Gy in five fractions of 2.00 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. A percentage (36.7%) of the patients had previously received laser treatments in the study eye, 21.9% once, 5% twice, 9.7% three or more. Subjective visual acuity and toxicity data was collected on all patients. Results: At 2-3 weeks after treatment 195 patients (70%) retained their visual acuity without change, 68 patients (24.5%) stated they had improved vision, and 15 patients (4.8%) stated their vision continued to decrease. Two to 3 months after treatment, 183 patients (65.8%) had no change in their vision. 75 patients (27%) patients had an improvement in their vision, and 20 patients (7.2%) had a decrease in visual acuity. Transient acute reactions occurred in 14 of the 278 patients treated. Conclusion: Our observations in this group of 278 patients support the conclusion

  2. The macular threshold protocol of the Humphrey visual field analyzer: a superior functional outcome of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration Desfecho funcional superior da eficácia do tratamento com bevacizumab intravítreo em degeneração macular relacionada à idade, por meio do protocolo de limiar macular do campímetro de Humphrey

    OpenAIRE

    Fabio Lavinsky; Micheal John Tolentino; Jaco Lavinsky

    2010-01-01

    PURPOSE: To evaluate the decibel loss on the Macular threshold protocol of the Humphrey visual field as a reliable functional outcome of the intravitreal bevacizumab treatment. METHODS: Thirteen patients were evaluated at baseline and on the week 6 for best corrected visual acuity, optical coherence tomography central macular thickness and decibel loss on Macular threshold protocol of the Humphrey visual field after 1.25 mg intravitreal injection of bevacizumab. The outcomes were analyzed sep...

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

    Directory of Open Access Journals (Sweden)

    Bunce Catey

    2008-10-01

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

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

    OpenAIRE

    Chen, Mei; Xu, Heping

    2015-01-01

    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 le...

  5. Radiation therapy for age-related macular degeneration (ARMD)

    International Nuclear Information System (INIS)

    Authors' results of low dose radiation therapy for ARMD were described. CT scan simulation was performed to determine the irradiation field of posterior pole of eyeball to which more than 90% of radiation was to be absorbed. The photon beam of 6MV was irradiated as to avoid lens at 2 Gy/day for 1 or 2 weeks to attain 10 or 20 Gy in total, respectively. After the treatment, the process was followed every 3 months and examinations with fluorescence contrasting, for visual field and for adverse radiation effects were done every 6 months. Results of reduction, no change and increase of choroidal neovascularization plate within 1 y were seen in 7 (47%), 4 (27%) and 4 eyes (27%) per total 15 eyes, respectively, in the treated group with 10 Gy whereas those in the control untreated group were 1 (6%), 6 (35%) and 10 (59%) eyes per 17 eyes, respectively (P<0.05). In addition, the treatment was effective for improvement of serous abruption and of retinal edema and for keeping optesthesia. The radiation therapy with 20 Gy was one too recently introduced to give enough results but may be more promising. (K.H.)

  6. Radiation therapy for age-related macular degeneration (ARMD)

    Energy Technology Data Exchange (ETDEWEB)

    Mandai, Michiko; Ogura, Yuichiro [Kyoto Univ. (Japan). Faculty of Medicine

    1996-09-01

    Authors` results of low dose radiation therapy for ARMD were described. CT scan simulation was performed to determine the irradiation field of posterior pole of eyeball to which more than 90% of radiation was to be absorbed. The photon beam of 6MV was irradiated as to avoid lens at 2 Gy/day for 1 or 2 weeks to attain 10 or 20 Gy in total, respectively. After the treatment, the process was followed every 3 months and examinations with fluorescence contrasting, for visual field and for adverse radiation effects were done every 6 months. Results of reduction, no change and increase of choroidal neovascularization plate within 1 y were seen in 7 (47%), 4 (27%) and 4 eyes (27%) per total 15 eyes, respectively, in the treated group with 10 Gy whereas those in the control untreated group were 1 (6%), 6 (35%) and 10 (59%) eyes per 17 eyes, respectively (P<0.05). In addition, the treatment was effective for improvement of serous abruption and of retinal edema and for keeping optesthesia. The radiation therapy with 20 Gy was one too recently introduced to give enough results but may be more promising. (K.H.)

  7. Early detection of choroidal neovascularization in age related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tural Galbinur

    2014-07-01

    Full Text Available Purpose: to identify factors associated with early detection of choroidal neovascularization CNV in clinical practice.Methods: Seventy six AMD patients who had history of CNV in one eye and presented with CNV in the second eye and evaluated for association with visual acuity (VA at time of presentation. Demographics, clinical data and lesion characteristics were retrospectively collected.Results: Better VA was associated with history of CNV in the fellow eye (p<0.0001, adherence to follow-up every four-months (p=0.015, younger age (p=0.03, smaller lesion (p<0.0001, and non-subfoveal localization (p=0.048. VA of the fellow eye did not correlate with VA at presentation with CNV.Conclusion: these data suggest that experience of CNV, regardless of VA, facilitates early diagnosis in the fellow eye. Adherence to follow-up in the routine clinic setting also facilitates early detection of CNV.

  8. Early detection of choroidal neovascularization in age related macular degeneration

    OpenAIRE

    Tural Galbinur

    2014-01-01

    Purpose: to identify factors associated with early detection of choroidal neovascularization CNV in clinical practice.Methods: Seventy six AMD patients who had history of CNV in one eye and presented with CNV in the second eye and evaluated for association with visual acuity (VA) at time of presentation. Demographics, clinical data and lesion characteristics were retrospectively collected.Results: Better VA was associated with history of CNV in the fellow eye (p<0.0001), adherence to follo...

  9. Clinical Efficacy of Combined Photodynamic Therapy and Intravitreal Triamcinolone Acetonide for Age-Related Macular Degeneration%光动力疗法联合曲安奈德治疗渗出型老年性黄斑变性的疗效观察

    Institute of Scientific and Technical Information of China (English)

    唐晓蕾; 王晓莉; 杨衡

    2012-01-01

    目的 评估光动力疗法联合曲安奈德治疗渗出型老年性黄斑变性(AMD)的临床疗效及对患者生活质量的影响.方法 将2007年12月-2010年12月就诊的35例(38只眼)渗出型AMD患者采用随机数字表法随机分为两组,治疗组18例(20只眼)采用光动力疗法联合玻璃体腔内注射曲安奈德治疗,对照组17例(18只眼)单用光动力疗法.评估患者视力和眼底影像学改变,同时也评估对患者生活质量的影响.两组均随访12个月.结果 随访12个月后,光动力疗法联合曲安奈德治疗组视力不变者8例9只眼,占45.0%;视力提高者9例10只眼,占50.0%;视力下降者1例1只眼,占5.0%.吲哚青绿血管造影结果显示,脉络膜新生血管(CNV)漏停止7例7只眼,占35.0%;持续渗漏或渗漏增加者1例1只眼,占5.0%;渗漏减少者11例12只眼,占60.0%.光动力疗法治疗组视力不变者6例6只眼,占33.3%;视力提高者4例5只眼,占27.8%;视力下降者7例7只眼,占38.9%.吲哚青绿血管造影结果显示,CNV渗漏停止3例3只眼,占16.7%;持续渗漏或渗漏增加者5例6只眼,占33.3%;渗漏减少者9例9只眼,占50.0%.联合治疗组与单用光动力疗法组在视力改变方面差异有统计学意义(x2=4.67,P=0.03),在吲哚青绿血管造影结果方面差异有统计学意义(x2=3.35,P=0.01).中文译本低视力者生存质量量表评估生活质量治疗组平均得分(102.02±16.20)分,对照组平均得分为(91.27±11.81)分,两组比较差异有统计学意义(P<0.05).结论 光动力疗法联合曲安奈德治疗渗出型AMD疗效优于单用光动力疗法.%Objective To investigate the efficacy of combined photodynamic therapy and intravitreal triamcinolone acetonide for age-related macular degeneration and its influence on patients' life quality. Methods Thirty-five patients (38 eyes) with age-related macular degeneration treated in our hospital from December 2007 to December 2010 were

  10. 补体替代途径中相关因子的激活与年龄相关性黄斑变性的关系%Relationship between some relative factors of the complement alternative pathway and age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    葛慧敏; 李芳

    2014-01-01

    Age related macular degeneration ( AMD) is a degenerative disease with the pathological changes in macula lutea and finally leads to the blurred vision even blindness.Environmental and inflammatory reaction may be related with its development.However the exact etiology of the diseases is not clear.AMD is likely a local response of complement alterna-tive pathway which responds to certain systemic inflammatory diseases.Complement component 3 ( C3 ) , complement factor H (CFH), complement factor H-related 1 and 3 (CFHR1 and CFHR3), complement factor B (CFB), and complement factor I ( CFI) are important components in the complement system and also the keys to the pathogenesis of AMD.This re-view is aiming to clarify possible functions of these factors based on recent research.%年龄相关性黄斑变性( age related macular dengeneration, AMD)是一种与年龄相关的黄斑区退行性病变,最终可导致视力模糊甚至丧失。 AMD的发生受到环境和体内炎症反应综合影响,但其具体发病机制至今仍不清楚,目前研究发现由补体替代途径所介导的炎症反应可能起到关键作用。 C3( complement component 3)、H因子(complement factor H,CFH)、H因子相关蛋白1和3(complement factor H-related 1 and 3,CFHR1 and CFHR3)、B因子(complement factor B,CFB)、I因子(complement factor I,CFI)在替代途径的激活过程中起到了重要的调节作用。CFH可协同由CFI介导的C3 b的裂解过程从而抑制C3转化酶形成,阻滞替代途径的激活。 CFHR1和CFHR3作为CFH竞争性因子与CFH争夺C3 b上的靶位点并可与CFI协同作用影响补体替代途径的激活。 CFB和C3是补体替代途径中的关键因子与AMD中补体替代途径的激活有着密不可分的关系。本文就上述因子的激活在AMD发病过程中的作用进行综述。

  11. Microcurrent stimulation in the treatment of dry and wet macular degeneration

    Directory of Open Access Journals (Sweden)

    Chaikin L

    2015-12-01

    Full Text Available Laurie Chaikin,1 Kellen Kashiwa,2 Michael Bennet,2 George Papastergiou,3 Walter Gregory4 1Private practice, Alameda, CA, USA; 2Retina Institute of Hawaii, Honolulu, HI, USA; 3California Retinal Associates, San Diego, CA, USA; 4Clinical Trials Research Unit, Faculty of Medicine and Health, University of Leeds, Leeds, UK Purpose: To determine the safety and efficacy of the application of transcutaneous (transpalpebral microcurrent stimulation to slow progression of dry and wet macular degeneration or improve vision in dry and wet macular degeneration. Methods: Seventeen patients aged between 67 and 95 years with an average age of 83 years were selected to participate in the study over a period of 3 months in two eye care centers. There were 25 eyes with dry age-related macular degeneration (DAMD and six eyes with wet age-related macular degeneration (WAMD. Frequency-specific microcurrent stimulation was applied in a transpalpebral manner, using two programmable dual channel microcurrent units delivering pulsed microcurrent at 150 µA for 35 minutes once a week. The frequency pairs selected were based on targeting tissues, which are typically affected by the disease combined with frequencies that target disease processes. Early Treatment Diabetic Retinopathy Study or Snellen visual acuity (VA was measured before and after each treatment session. All treatment was administered in a clinical setting. Results: Significant increases were seen in VA in DAMD (P=0.012, Wilcoxon one-sample test, but in WAMD, improvements did not reach statistical significance (P=0.059. In DAMD eyes, twice as many patients showed increase in VA (52% compared to those showing deterioration (26%, with improvements being often sizeable, whereas deteriorations were usually very slight. In WAMD eyes, five of six (83% patients showed an increase and none showed deterioration. Conclusion: The substantial changes observed over this period, combined with continued improvement for

  12. The macular threshold protocol of the Humphrey visual field analyzer: a superior functional outcome of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration Desfecho funcional superior da eficácia do tratamento com bevacizumab intravítreo em degeneração macular relacionada à idade, por meio do protocolo de limiar macular do campímetro de Humphrey

    Directory of Open Access Journals (Sweden)

    Fabio Lavinsky

    2010-04-01

    Full Text Available PURPOSE: To evaluate the decibel loss on the Macular threshold protocol of the Humphrey visual field as a reliable functional outcome of the intravitreal bevacizumab treatment. METHODS: Thirteen patients were evaluated at baseline and on the week 6 for best corrected visual acuity, optical coherence tomography central macular thickness and decibel loss on Macular threshold protocol of the Humphrey visual field after 1.25 mg intravitreal injection of bevacizumab. The outcomes were analyzed separately and in correlation using the Wilcoxon signed ranks test. RESULTS: The improvement of the optical coherence tomography and the Macular threshold protocol of the Humphrey visual field from baseline to week 6 were significant with p=0.032 and p=0.003, respectively. The visual acuity did not show a significant improvement. The correlation of the visual acuity and Macular threshold protocol of the Humphrey visual field was significant at baseline (p=0.041 and on week 6 (p=0.019. CONCLUSION: The Macular threshold protocol of the Humphrey visual field significantly improved despite the fact that the best corrected visual acuity did not. The Macular threshold protocol of the Humphrey visual field correlated with the visual acuities significantly. The optical coherence tomography was significant to demonstrate improvement but did not correlate with best corrected visual acuity and Macular threshold protocol of the Humphrey visual field. These findings suggest that the Macular threshold protocol of the visual field may be a more reliable tool for evaluation of global macular function after intravitreal bevacizumab treatment.OBJETIVO: Avaliar se a perda de decibéis no protocolo macular do campímetro de Humphrey (PMCH é um resultado funcional confiável para o tratamento com bevacizumab intravítreo. MÉTODOS: Treze pacientes foram avaliados na visita de base e na semana 6 após a injeção intravítrea de 1,25 mg de bevacizumab realizando a melhor acuidade

  13. The value of optical coherence tomography in diagnosis and therapy of age-related degeneration

    International Nuclear Information System (INIS)

    The ophthalmologic departments are confronted by the necessity of an increasing number of Fluorescein Angiograms (FA). It should be examined in which cases the FA might be replaced by the Optical Coherence Tomography (OCT). FA and OCT examinations were retrospectively evaluated concerning composition, size and activity of the lesion. Unselected cases with age-related macular degeneration (AMD) who underwent FA within 1 month were retrospectively examined, prior examinations of these patients were also evaluated. According to the results of the FA the patients were assigned to different subgroups. 150 FA and OCT examinations of 50 patients were included. In 12 eyes with non exsudative AMD there was a 100 % consistency of the diagnosis. In 68 examinations of 42 eyes with occult exsudative AMD the consistency concerning lesion composition was 78%, differences were noted in the presence of retinal angiomatous proliferation, minimal classic parts, the presence of fibrosis. The evaluation of the activity showed differences of less than two steps in 97 %. In 24 examinations of 16 eyes treated with antiangiogenetic substances the activity of a lesion was judged to be equal in 75%. In 96 % the indication for re-treatment was identical in both examinations. Both examinations FA and OCT were necessary to evaluate a case concerning composition and activity of a lesion. Measurement of the greatest diameter of the lesion was not possible with the OCT except in predominantly classic lesions. In cases treated with antiangiogenetic substances OCT alone provided enough information to decide whether re-treatment is necessary. (author)

  14. Ernest Borgnine Lays it on the Line Hollywood Hero Focuses on Macular Degeneration

    Science.gov (United States)

    ... it on the Line Hollywood Hero Focuses on Macular Degeneration Past Issues / Summer 2008 Table of Contents For ... going strong at 91, and speaking out on macular degeneration for the National Eye Institute. Photo courtesy of ...

  15. Detection and significance of serum angiogenesis regulatory cytokines in patients of exudative age-related macular degeneration%渗出型年龄相关性黄斑变性患者血清新生血管调控细胞因子水平变化及意义

    Institute of Scientific and Technical Information of China (English)

    陈烨; 李薇薇; 于小蕊; 田蓓; 魏文斌; 巢国俊

    2015-01-01

    目的 探讨血清新生血管调控相关细胞因子在渗出型年龄相关性黄斑变性(exudative age-related macular degeneration,eAMD)发病中的作用.方法 采用双抗体夹心ELISA法检测51例eAMD患者(eAMD组)血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、血小板衍生生长因子(platelet derived growth factor,PDGF)、基质金属蛋白酶抑制剂-1 (tissue inhibitor of matrix metalloproteinase-1,TIMP-1)、内皮抑素(endostatin,ES)水平,并与20例体检健康者(对照组)进行比较.结果 eAMD组血清VEGF[(165.14±100.44) ng/L]、PDGF[(62.18±16.94)μg/L]水平高于对照组[VEGF(64.90±19.74) ng/L、PDGF(39.25±8.39)μg/L] (P<0.01),TIMP-1[(76.33±21.63)μg/L]与对照组[(76.61±13.25)μg/L]比较差异无统计学意义(P>0.05),ES[(139.02±40.20) ng/L]低于对照组[(160.85±43.50) ng/L],但差异无统计学意义(P>0.05);ES/VEGF(1.03±0.61)、ES/PDGF比值(2.34±0.88)均较对照组(2.78±1.25、4.34±1.69)降低(P<0.01);对照组VEGF与ES呈负相关(r=-0.700,P=0.002),eAMD组患者血清VEGF与PDGF呈正相关(r=0.610,P=0.000).结论 eAMD患者新生血管细胞因子调节失衡与其脉络膜新生血管发生、发展相关;联合检测血清VEGF、ES、PDGF、TIMP水平对指导eAMD治疗有临床意义.

  16. Radiation therapy in the treatment of macular degeneration: a review

    International Nuclear Information System (INIS)

    Macular degeneration is a major health problem. Less than 10 % of the cases can be successfully treated by laser therapy. Low dose radiation therapy (in the range of 20 Gy) appears to decrease neo-vascularization. These early results need to be confirmed through a randomized trial. (author)

  17. Role of ranibizumab in management of macular degeneration

    Directory of Open Access Journals (Sweden)

    Singh Rishi

    2007-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the most common causes of severe vision loss in the western world. Both animal and human studies have established that vascular endothelial growth factor (VEGF plays an important role in the pathogenesis of this process. Ranibizumab (Lucentis™, Genentech, South San Francisco, CA is a monoclonal antibody fragment (Fab directed toward all isoforms of VEGF-A that was specifically designed to target wet AMD. The human antibody fragment is produced by an E. coli expression system and has a molecular weight of 48kD allowing for excellent retinal penetration. The most common ocular complaints of patients receiving ranibizumab injections in randomized clinical trials were transient conjunctival hemorrhage, vitreous floaters, intraocular inflammation, increased intraocular pressure and eye pain. The rates of serious adverse events such as retinal detachment, cataract and endophthalmitis were similar to those that have been reported with other intravitreal injections and patients should always be treated under strict aseptic conditions to reduce this risk. There were no significant non-ocular events found during any study so far and the risk of thromboembolic events was less than 4% and not different than sham. The MARINA, ANCHOR and PIER studies validated the safety and efficacy of ranibizumab amongst a large population with different choroidal neovascular membrane lesion types against sham or standard of care treatment. These studies recommended monthly intravitreal ranibizumab for patients. However, the PIER study reported that an alternative dosing of every three months is acceptable but less effective than monthly injections.

  18. Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration

    OpenAIRE

    Yu, Yi; Triebwasser, Michael P.; Wong, Edwin K.S.; Schramm, Elizabeth C.; Thomas, Brett; Reynolds, Robyn; Elaine R Mardis; John P Atkinson; 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...

  19. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment.

    Science.gov (United States)

    Nolan, John M; Stack, Jim; O' Donovan, Orla; Loane, Edward; Beatty, Stephen

    2007-01-01

    Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM). This study was undertaken to investigate MP optical density with respect to risk factors for ARM, in 828 healthy subjects from an Irish population. MP optical density was measured psychophysically using heterochromatic flicker photometry, serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed using a validated food-frequency questionnaire. Clinical and personal details were also recorded, with particular attention directed towards risk factors for ARM. We report a statistically significant age-related decline in MP optical density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical density than never smokers and this difference was statistically significant (p<0.01). Subjects with a confirmed family history of ARM had significantly lower levels of MP optical density than subjects with no known family history of disease (p<0.01). For each of these established risk factors, their statistically significant negative association with MP persisted after controlling for the other two, and also after controlling for other potentially confounding variables such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal pathology, and in advance of disease onset, the relative lack of MP seen in association with increasing age, tobacco use and family history of ARM supports the hypothesis that the enhanced risk that these variables represent for ARM may be attributable, at least in part, to a parallel deficiency of macular carotenoids. PMID:17083932

  20. Visual Prosthesis for Macular Degeneration And Retinistis Pigmentosa

    OpenAIRE

    Shweta Gupta; Shashi Kumar Singh; V.K. Dwivedi

    2014-01-01

    Abstract: This paper incorporates majorly visual prosthesis that results in electronic solution such as bionic eye for the disease macular degeneration and retinitis pigmentosa. Both diseases damage the eyes’ photoreceptors, the cells at the back of the retina that perceive light patterns and pass them on to the brain in the form of nerve impulses, where the impulse patterns are then interpreted as images. The Argus II system takes the place of these photoreceptors. In the past 20 years, biot...