scholarly journals Association between Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration

2019 ◽  
Author(s):  
Johanna M. Seddon ◽  
James Dossett ◽  
Rafael Widjajahakim ◽  
Bernard Rosner
Keyword(s):  
Macular Degeneration ◽  
Genetic Variants ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Density Lipoprotein ◽  
Age Related Macular Degeneration ◽  
Quantitative Classification ◽  
Age Related ◽  
Common Genetic Variants ◽  
Area And Volume

ABSTRACTPURPOSETo determine associations between macular drusen parameters derived from an automatic optical coherence tomography (OCT) algorithm, age-related macular degeneration (AMD) stage and genetic variants.METHODSEyes classified as early or intermediate AMD with OCT imaging and genetic data were selected (n=239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium (RPE) analysis algorithm in a 5mm diameter (perifoveal) zone centered on the fovea. Associations between drusen measurements and common genetic variants in the complement and high density lipoprotein (HDL) lipid pathways and the ARMS2 variant were calculated using generalized estimating equations and linear mixed models adjusting for age, sex, smoking, BMI, and education.RESULTSWhen compared to eyes with no measurable drusen, drusen area ≥ the median was independently associated with a higher number of risk alleles for CFH risk score, risk variants in C3 and ARMS2/HTRA1. Similar results were obtained for drusen volume. When all genes were analyzed in the same model, only CFH score and ARMS2/HTRA1 were associated with drusen measurements. HDL pathway genes were not significantly related to drusen parameters. Early and intermediate AMD stages were associated with OCT derived drusen area and volume.CONCLUSIONGenetic variants in CFH and ARMS2/HTRA1, commonly associated with advanced AMD, were independently associated with higher drusen burden determined by OCT in eyes with early and intermediate AMD. The automatic RPE algorithm using OCT provides a quantitative classification of non-advanced AMD. Drusen morphology and other OCT-derived sub-phenotypes are biomarkers that could provide early anatomic endpoints for clinical trials.

scholarly journals Dry Age-Related Macular Degeneration – A New Approach In Optical Coherence Tomography Monitoring And Quantitative Assessment

2014 ◽  
Vol 7 (2) ◽  
pp. 148-154
Author(s):  
Elitsa G. Hristova ◽  
Zornitsa I. Zlatarova
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Three Dimensional ◽  
Software Tool ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Dry Amd ◽  
Area And Volume

Summary The purpose of the study was to present the ability of Drusen analysis software tool to measure drusen area and volume in patients with dry age-related macular degeneration (AMD). Eleven patients with confirmed dry AMD aged 59-74 years were scanned with 3D OCT-2000 Topcon 3D Macula scanning protocol by a single operator. All subjects underwent a complete ophthalmologic examination including best corrected visual acuity, indirect biomicroscopy, tonometry, fluorescein angiography and OCT. Drusen analysis was performed on the macula with 6.0 × 6.0 mm volume cube scans and 512×128 pixels scan resolution. The results were presented along with calculated values in two clearly arranged reports. Mean follow-up period was 19 months (6-40). Count, area occupation, volume of the drusen and 3D retinal pigment epithelium (RPE) elevation map were presented in a Macula drusen analysis report. Drusen count and volume in 6 patients were increased at the end of follow-up period. There were 5 patients with regression in drusen count and area and volume of the drusen in 3 of them were higher than on previous examination. Another 2 were with regression not only in drusen count but also in their area and volume. With this software tool the status of RPE can be objectively and automatically examined in detail and can be followed up over time. OCT allows for precise quantitative evaluation and study of microstructural changes in patients with dry AMD and provides three-dimensional information of macular pathology in situ and in real time. This could be useful for determining stages and monitoring the progression of AMD.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

scholarly journals Retinal Pigment Epithelium Expressed Toll-like Receptors and Their Potential Role in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (16) ◽  
pp. 8387
Author(s):  
Alexa Klettner ◽  
Johann Roider
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Current Status ◽  
Toll Like Receptors ◽  
Cell Degeneration ◽  
Age Related

(1) Background: Inflammation is a major pathomechanism in the development and progression of age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) may contribute to retinal inflammation via activation of its Toll-like receptors (TLR). TLR are pattern recognition receptors that detect the pathogen- or danger-associated molecular pattern. The involvement of TLR activation in AMD is so far not understood. (2) Methods: We performed a systematic literature research, consulting the National Library of Medicine (PubMed). (3) Results: We identified 106 studies, of which 54 were included in this review. Based on these studies, the current status of TLR in AMD, the effects of TLR in RPE activation and of the interaction of TLR activated RPE with monocytic cells are given, and the potential of TLR activation in RPE as part of the AMD development is discussed. (4) Conclusion: The activation of TLR2, -3, and -4 induces a profound pro-inflammatory response in the RPE that may contribute to (long-term) inflammation by induction of pro-inflammatory cytokines, reducing RPE function and causing RPE cell degeneration, thereby potentially constantly providing new TLR ligands, which could perpetuate and, in the long run, exacerbate the inflammatory response, which may contribute to AMD development. Furthermore, the combined activation of RPE and microglia may exacerbate neurotoxic effects.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

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