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https://www.readbyqxmd.com/read/29782502/a-monoclonal-antibody-targeting-amyloid-%C3%AE-a%C3%AE-restores-complement-factor-i-bioactivity-potential-implications-in-age-related-macular-degeneration-and-alzheimer-s-disease
#1
Kameran Lashkari, Gianna Teague, Hong Chen, Yong-Qing Lin, Sanjay Kumar, Megan M McLaughlin, Francisco J López
Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies...
2018: PloS One
https://www.readbyqxmd.com/read/29746403/amish-eye-study-baseline-spectral-domain-optical-coherence-tomography-characteristics-of-age-related-macular-degeneration
#2
Muneeswar G Nittala, Yeunjoo E Song, Rebecca Sardell, Larry D Adams, Samuel Pan, Swetha B Velaga, Violet Horst, Debra Dana, Laura Caywood, Renee Laux, Denise Fuzzell, Sarada Fuzzell, William K Scott, Jessica N Cooke Bailey, Robert P Igo, Jonathan Haines, Margaret A Pericak-Vance, SriniVas R Sadda, Dwight Stambolian
PURPOSE: To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). METHODS: The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography...
May 9, 2018: Retina
https://www.readbyqxmd.com/read/29739345/atypical-central-retinal-artery-occlusion-as-the-first-presentation-of-poems-syndrome-a-case-report
#3
Panitha Jindahra, Charungthai Dejthevaporn, Pimjai Niparuck, Jariya Waisayarat, Piyaphon Cheecharoen, Thanatporn Threetong, Purit Petpiroon, Tharikarn Sujirakul, Anuchit Poonyathalang, Kavin Vanikieti
BACKGROUND: POEMS syndrome is a plasma cell disorder, which clinically manifests from paraneoplastic syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. The most common ocular manifestation is optic disc swelling, whereas other ocular manifestations; cystoid macular edema, serous macular detachment, venous sinus thrombosis, infiltrative orbitopathy, uveitis, neovascularization of the disc, peripapillary choroidal neovascularization and optic disc drusen, had also been reported...
May 8, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29730901/htra1-an-age-related-macular-degeneration-protease-processes-extracellular-matrix-proteins-efemp1-and-tsp1
#4
Michael K Lin, Jin Yang, Chun Wei Hsu, Anuradha Gore, Alexander G Bassuk, Lewis M Brown, Ryan Colligan, Jesse D Sengillo, Vinit B Mahajan, Stephen H Tsang
High-temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age-related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key...
May 5, 2018: Aging Cell
https://www.readbyqxmd.com/read/29725335/c-reactive-protein-as-a-therapeutic-target-in-age-related-macular-degeneration
#5
REVIEW
Blanca Molins, Sara Romero-Vázquez, Pablo Fuentes-Prior, Alfredo Adan, Andrew D Dick
Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29721942/the-role-of-hypoxia-hypoxia-inducible-factor-hif-and-vegf-in-retinal-angiomatous-proliferation
#6
Maya Barben, Marijana Samardzija, Christian Grimm
In industrialized countries, age-related macular degeneration (AMD) is the leading cause of blindness in elderly people. Hallmarks of the non-neovascular (dry) form of AMD are the formation of drusen and geographic atrophy, whereas the exudative (wet) form of the disease is characterized by invading blood vessels. In retinal angiomatous proliferation (RAP), a special form of wet AMD, intraretinal vessels grow from the deep plexus into the subretinal space. Little is known about the mechanisms leading to intraretinal neovascularization, but age-related changes such as reduction of choroidal blood flow, accumulation of drusen, and thickening of the Bruch's membrane may lead to reduced oxygen availability in photoreceptors...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721926/anaphylatoxin-signaling-in-retinal-pigment-and-choroidal-endothelial-cells-characteristics-and-relevance-to-age-related-macular-degeneration
#7
Bärbel Rohrer
Age-related macular degeneration (AMD) is the leading cause of blindness in the USA. Polymorphisms in various complement components are associated with an increased risk for AMD, and it has been hypothesized that an overactive complement system is partially responsible for the pathology of AMD. AMD is classified as early, intermediate, or late AMD, depending on the degree of the associated pathologies. Late AMD can be characterized as either lesions associated with neovascular AMD or geographic atrophy. Both sets of lesions are associated with pathology at the RPE/choroid interface, which include a thickening of Bruch's membrane, presence of drusen, and pigmentary alterations, and deterioration of the blood-retina barrier has been reported...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721924/alterations-in-extracellular-matrix-bruch-s-membrane-can-cause-the-activation-of-the-alternative-complement-pathway-via-tick-over
#8
Rosario Fernandez-Godino
Given the complex etiology of age-related macular degeneration (AMD), treatments are developed to target intermediate/late stages of the disease. Unfortunately, the design of therapies for early stages of the disease is limited by our understanding of the mechanisms involved in the formation of basal deposits and drusen, the first clinical signs of AMD. During the last decade, the identification of common and rare alleles in complement genes as risk AMD variants in addition to the presence of active complement components in basal deposits and drusen has provided compelling evidence that the complement system plays a key role in the pathobiology of AMD...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721037/automated-segmentation-methods-of-drusen-to-diagnose-age-related-macular-degeneration-screening-in-retinal-images
#9
Young Jae Kim, Kwang Gi Kim
Existing drusen measurement is difficult to use in clinic because it requires a lot of time and effort for visual inspection. In order to resolve this problem, we propose an automatic drusen detection method to help clinical diagnosis of age-related macular degeneration. First, we changed the fundus image to a green channel and extracted the ROI of the macular area based on the optic disk. Next, we detected the candidate group using the difference image of the median filter within the ROI. We also segmented vessels and removed them from the image...
2018: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/29708976/factors-associated-with-visual-field-defects-of-optic-disc-drusen
#10
Kyoung Min Lee, Se Joon Woo, Jeong-Min Hwang
PURPOSE: To investigate the prevalence and risk factors for visual field defect in patients with optic disc drusen (ODD). METHODS: We assessed the visual field status of patients with ODD whose diagnosis were confirmed by spectral-domain optical coherence tomography (SD-OCT). Visual field defects were classified as normal, enlarged blind spot, or other defects. ODD were classified into either type 1 (without hyperreflective border and heterogenic internal reflectance) or type 2 (with hyperreflective border and lower internal reflectance)...
2018: PloS One
https://www.readbyqxmd.com/read/29706603/impact-of-drusen-and-drusenoid-retinal-pigment-epithelium-elevation-size-and-structure-on-the-integrity-of-the-retinal-pigment-epithelium-layer
#11
Schlanitz Ferdinand, Bernhard Baumann, Stefan Sacu, Lukas Baumann, Michael Pircher, Christoph K Hitzenberger, Ursula Margarethe Schmidt-Erfurth
PURPOSE: To evaluate the impact of drusen size and structure on retinal pigment epithelium (RPE) and photoreceptor layers in eyes with early to intermediate age-related macular degeneration (AMD) using polarisation-sensitive optical coherence tomography (OCT). DESIGN: Retrospective investigation of an observational cross-sectional study. PARTICIPANTS: Patients with early to intermediate AMD. METHODS: Twenty-five eyes of 25 patients with drusen were imaged with polarisation-sensitive OCT using macular volume scans...
April 29, 2018: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29706360/whole-exome-sequencing-in-age-related-macular-degeneration-identifies-rare-variants-in-col8a1-a-component-of-bruch-s-membrane
#12
Jordi Corominas, Johanna M Colijn, Maartje J Geerlings, Marc Pauper, Bjorn Bakker, Najaf Amin, Laura Lores Motta, Eveline Kersten, Alejandro Garanto, Joost A M Verlouw, Jeroen G J van Rooij, Robert Kraaij, Paulus T V M de Jong, Albert Hofman, Johannes R Vingerling, Tina Schick, Sascha Fauser, Eiko K de Jong, Cornelia M van Duijn, Carel B Hoyng, Caroline C W Klaver, Anneke I den Hollander
PURPOSE: Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited...
April 26, 2018: Ophthalmology
https://www.readbyqxmd.com/read/29694963/treatment-of-macular-degeneration-with-sildenafil-results-of-a-two-year-trial
#13
D Jackson Coleman, Winston Lee, Stanley Chang, Ronald H Silverman, Harriet O Lloyd, Suzanne Daly, Stephen H Tsang
OBJECTIVE: To evaluate PDE5/6 inhibition with sildenafil to reduce choroidal ischemia and treat age-related macular degeneration. METHODS: Sildenafil was prescribed to treat participants with macular degenerations or macular dystrophies measured by spectral-domain optical coherence tomography, color fundus photography, enhanced depth imaging, and best-corrected visual acuity. RESULTS: No change in calcified drusen was noted. Vitelliform-type soft drusen were not substantially changed...
April 25, 2018: Ophthalmologica. Journal International D'ophtalmologie
https://www.readbyqxmd.com/read/29659172/optic-disc-drusen-understanding-an-old-problem-from-a-new-perspective
#14
REVIEW
Steffen Hamann, Lasse Malmqvist, Fiona Costello
Optic disc drusen (ODD) are acellular deposits located in the optic nerve head of up to 2.4% of the population. They may develop as by-products of impaired axonal metabolism in genetically predisposed individuals, in whom a narrow scleral canal is hypothesized to play a role. Although ODD are often considered as benign innocent bystanders, recognized as part of a routine ophthalmological examination, the vast majority of patients with ODD have visual field defects. Optic disc drusen (ODD)-associated complications with severe visual loss, most often due to anterior ischaemic optic neuropathy, are also known to occur...
April 16, 2018: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29649006/the-influence-of-volume-and-anatomic-location-of-optic-disc-drusen-on-the-sensitivity-of-autofluorescence
#15
Frederik Cornelius Loft, Lasse Malmqvist, Anne-Sofie Wessel Lindberg, Steffen Hamann
BACKGROUND: Optic disc drusen (ODD) are acellular deposits in the optic nerve head. ODD can be diagnosed using different imaging modalities, including enhanced depth imaging optical coherence tomography (EDI-OCT) and autofluorescence (AF). It is unknown which factors determine the sensitivity of AF. The aim of this study was to investigate the effect of volume and anatomic location of ODD on the sensitivity of AF. METHODS: Cross-sectional study. RESULTS: A total of 38 patients (75 eyes) with ODD were included...
April 11, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29643786/association-of-optic-nerve-head-drusen-with-best-vitelliform-macular-dystrophy-a-case-series
#16
Robert J White, Daniel J Watson, Dara D Koozekanani, Sandra R Montezuma
Purpose: To report the association of optic nerve head (ONH) drusen with Best vitelliform macular dystrophy (BVMD). Methods: Chart review. Patients: Five patients from 3 families. Results: Multimodal imaging and ophthalmic examination demonstrated findings consistent with ONH drusen, in association with BVMD, in 5 patients. Conclusion: We report the association of BVMD with ONH drusen in 5 patients...
January 2018: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/29625486/structure-function-analysis-in-patients-with-intermediate-age-related-macular-degeneration
#17
Marlene Saßmannshausen, Julia S Steinberg, Rolf Fimmers, Maximilian Pfau, Sarah Thiele, Monika Fleckenstein, Frank G Holz, Steffen Schmitz-Valckenberg
Purpose: To examine the topographic correlation between retinal morphology and retinal sensitivity by mesopic and scotopic fundus-controlled perimetry (FCP) in eyes with intermediate AMD. Methods: Thirty-five eyes from 32 patients (mean age 70.9 years) and 29 age-matched controls prospectively underwent spectral-domain optical coherence tomography (SD-OCT) imaging. Mesopic (Goldman III, 200 ms, 4-2 strategy) and scotopic (Goldman V, 200 ms, 4-2 strategy) FCP with a 56-stimulus point grid was performed in AMD patients with the MP-1S...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29621759/peripheral-retinal-imaging-biomarkers-for-alzheimer-s-disease-a-pilot-study
#18
Lajos Csincsik, Thomas J MacGillivray, Erin Flynn, Enrico Pellegrini, Giorgos Papanastasiou, Neda Barzegar-Befroei, Adrienne Csutak, Alan C Bird, Craig W Ritchie, Tunde Peto, Imre Lengyel
PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL...
April 5, 2018: Ophthalmic Research
https://www.readbyqxmd.com/read/29621510/peripheral-changes-associated-with-delayed-dark-adaptation-in-age-related-macular-degeneration
#19
Inês Laíns, Dong Ho Park, Ryo Mukai, Rebecca Silverman, Patrick Oellers, Steven Mach, Ivana K Kim, Demetrios G Vavvas, Joan W Miller, John B Miller, Deeba Husain
PURPOSE: To study the association between peripheral changes in Age-related Macular Degeneration (AMD) and dark adaptation (DA). DESIGN: Prospective, cross-sectional study. METHODS: We recruited patients with AMD and a control group (> 50 years) without any vitreoretinal disease. Ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) (Optos Inc, MA) were obtained, and were assessed by two graders for the presence of several peripheral changes in perimacular, mid- and far-peripheral zones...
April 2, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29610844/multispectral-pattern-recognition-reveals-a-diversity-of-clinical-signs-in-intermediate-age-related-macular-degeneration
#20
Angelica Ly, Lisa Nivison-Smith, Nagi Assaad, Michael Kalloniatis
Purpose: To develop a proof-of-concept, computational method for the quantification and classification of fundus images in intermediate age-related macular degeneration (AMD). Methods: Multispectral, unsupervised pattern recognition was applied to 184 fundus images from 10 normal and 36 intermediate AMD eyes. The imaging results of preprocessed, grayscale images from three modalities (infrared, green, and fundus autofluorescence scanning laser ophthalmoscopy) were automatically classified into various clusters sharing a common spectral signature, using a k-means clustering algorithm...
April 1, 2018: Investigative Ophthalmology & Visual Science
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