scholarly journals Macular retinal thickness differs markedly in age-related macular degeneration driven by risk polymorphisms on chromosomes 1 and 10

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Moussa A. Zouache ◽  
Alex Bennion ◽  
Jill L. Hageman ◽  
Christian Pappas ◽  
Burt T. Richards ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Chromosome 1 ◽  
Risk Alleles ◽  
Risk Variants ◽  
Age Related ◽  
Similar Disease ◽  
Macular Retinal Thickness

AbstractThe two most common genetic contributors to age-related macular degeneration (AMD), a leading cause of irreversible vision loss worldwide, are variants associated with CFH-CFHR5 on chromosome 1 (Chr1) and ARMS2/HTRA1 on chromosome 10 (Chr10). We sought to determine if risk and protective variants associated with these two loci drive differences in macular retinal thickness prior and subsequent to the onset of clinically observable signs of AMD. We considered 299 individuals (547 eyes) homozygous for risk variants or haplotypes on Chr1 or Chr10 exclusively (Chr1-risk and Chr10-risk, respectively) or homozygous for a neutral haplotype (Chr1-neu), for the protective I62 tagged haplotype (Chr1-prot-I62) or for the protection conferring CFHR1/3 deletion haplotype (Chr1-prot-del) on Chr1 without any risk alleles on Chr10. Among eyes with no clinically observable signs of AMD, the deletion of CFHR1/3, which is strongly protective against this disease, is associated with significantly thicker retinas in the perifovea. When controlling for age, Chr10-risk eyes with early or intermediate AMD have thinner retinas as compared to eyes from the Chr1-risk group with similar disease severity. Our analysis indicates that this difference likely results from distinct biological and disease initiation and progression events associated with Chr1- and Chr10-directed AMD.

Long-term outcome of neovascular age-related macular degeneration: association between treatment outcome and major risk alleles

2021 ◽  
pp. bjophthalmol-2021-319054
Author(s):  
Brice Nguedia Vofo ◽  
Gala Beykin ◽  
Jaime Levy ◽  
Itay Chowers
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Long Term Outcome ◽  
Risk Alleles ◽  
Macular Atrophy ◽  
Anti Vegf ◽  
Age Related

AimsTo evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify associated risk factors.MethodsClinical and optical coherence tomography findings were retrieved for nvAMD cases treated with intravitreal anti-VEGF compounds using a treat-and-extend protocol. In addition, the major risk alleles for AMD in the CFH (rs1061170), HTRA1 (rs1200638) and C3 (rs2230199) genes were genotyped.ResultsFrom 276 eligible eyes in 206 patients, 80 eyes (29%) in 66 patients (32.0%) had a follow-up period of ≥8 years and were included in this study. Over a 10-year period, 73.3±28.0 (mean±SD) anti-VEGF injections were administered. Best-corrected visual acuity (BCVA; LogMAR) deteriorated from 0.55±0.53 at baseline to 1.00±0.73 at 10 years (p<0.0005). Central subfield thickness (CST) decreased from 415.8±162.1 µm at baseline to 323±113.6 µm (p<0.0005) after three monthly injections and remained lower than baseline throughout the follow-up period. Visual outcome was associated with BCVA and intraretinal fluid (IRF) at baseline, macular atrophy, and macular thinning at follow-up. The decrease in CST was inversely correlated with the number of CFH and/or C3 risk alleles carried by the patient (Pearson’s r: −0.608; p=0.003).ConclusionsPatients with nvAMD who received anti-VEGF therapy for 10 years developed substantial vision loss associated with the presence of IRF at baseline and macular atrophy. Major risk alleles for AMD in two complement genes were associated with a reduced long-term reduction in macular thickness.

scholarly journals New Qualitative Methods for Assessing the “Fluid” in the Retina in Age-Related Macular Degeneration

2021 ◽  
Vol 18 (2) ◽  
pp. 222-227
Author(s):  
M. V. Budzinskaya ◽  
A. A. Plyukhova
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Thickness ◽  
Antiangiogenic Therapy ◽  
Functional Results ◽  
Age Related Macular Degeneration ◽  
Modern World ◽  
Time Interval ◽  
Anti Vegf ◽  
Age Related

Age-related macular degeneration (AMD) is a chronic disease of the central retina and one of the main causes of blindness in patients over 60 years of age in industrialized countries. Currently, anti-vascular endothelial growth factor therapy (anti-VEGF therapy) has become the standard of neovascular AMD treatment, leading to the prevention of progressive vision loss in more than 90 % of treated patients during a two-year follow-up period. In the modern world there are transition from quantitative assessment of “fluid” according to optical coherence tomography (OCT) — the thickness of the central retinal zone, to qualitative — the presence of IRF, SRF, fluid under RPE. The data obtained by Zinkernagel have shown that, despite good functional results (an increase in visual acuity), the administration of the drug once every 2 months leads not only to fluctuations in IRF and SRF, but also to serous PED [4]. The existing qualitative and quantitative analysis is not perfect. Fluctuation is a new qualitative marker of the study of disease activity, it is defined as the sum of all types of fluid (IRF + SRF + fluid under RPE) in a certain time interval (with monthly measurement of the indicator). The fluctuation index was determined from the cumulative change in the thickness of the retina in the fovea over time [6]. Thus, the fluid is considered as a key morphological criterion for the activity of nVMD and an indication for (initiation or continuation) of antiangiogenic therapy. At the same time, there is evidence that a lower level of each type of fluid (IRF, SRF, fluid under RPE) is associated with better BCVA results against the background of anti-VEGF therapy [17]. The stability of retinal thickness during anti-VEGF therapy is no less important parameter than the statement of fluid resolution at a certain time, and it appears that better control of the central retinal thickness was associated with higher overall NEI VFQ-25 scores and individual scales reflecting important daily activities of the patient [16]. 

scholarly journals Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2/HTRA1 loci

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Chris M. Pappas ◽  
Moussa A. Zouache ◽  
Stacie Matthews ◽  
Caitlin D. Faust ◽  
Jill L. Hageman ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Full Spectrum ◽  
Tagging Snp ◽  
Risk Variants ◽  
Age Related ◽  
Functional Consequences ◽  
Risk Protection

Abstract Background Single-variant associations with age-related macular degeneration (AMD), one of the most prevalent causes of irreversible vision loss worldwide, have been studied extensively. However, because of a lack of refinement of these associations, there remains considerable ambiguity regarding what constitutes genetic risk and/or protection for this disease, and how genetic combinations affect this risk. In this study, we consider the two most common and strongly AMD-associated loci, the CFH-CFHR5 region on chromosome 1q32 (Chr1 locus) and ARMS2/HTRA1 gene on chromosome 10q26  (Chr10 locus). Results By refining associations within the CFH-CFHR5 locus, we show that all genetic protection against the development of AMD in this region is described by the combination of the amino acid-altering variant CFH I62V (rs800292) and genetic deletion of CFHR3/1. Haplotypes based on CFH I62V, a CFHR3/1 deletion tagging SNP and the risk variant CFH Y402H are associated with either risk, protection or neutrality for AMD and capture more than 99% of control- and case-associated chromosomes. We find that genetic combinations of CFH-CFHR5 haplotypes (diplotypes) strongly influence AMD susceptibility and that individuals with risk/protective diplotypes are substantially protected against the development of disease. Finally, we demonstrate that AMD risk in the ARMS2/HTRA1 locus is also mitigated by combinations of CFH-CFHR5 haplotypes, with Chr10 risk variants essentially neutralized by protective CFH-CFHR5 haplotypes. Conclusions Our study highlights the importance of considering protective CFH-CFHR5 haplotypes when assessing genetic susceptibility for AMD. It establishes a framework that describes the full spectrum of AMD susceptibility using an optimal set of single-nucleotide polymorphisms with known functional consequences. It also indicates that protective or preventive complement-directed therapies targeting AMD driven by CFH-CFHR5 risk haplotypes may also be effective when AMD is driven by ARMS2/HTRA1 risk variants.

scholarly journals Author Correction: Macular retinal thickness differs markedly in age-related macular degeneration driven by risk polymorphisms on chromosomes 1 and 10

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Moussa A. Zouache ◽  
Alex Bennion ◽  
Jill L. Hageman ◽  
Christian Pappas ◽  
Burt T. Richards ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Macular Retinal Thickness

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

Association between retinal thickness variation and visual acuity change in neovascular age‐related macular degeneration

2021 ◽  
Author(s):  
Kai Xiong Cheong ◽  
Alvin Wei Jun Teo ◽  
Chui Ming Gemmy Cheung ◽  
Issac Horng Khit Too ◽  
Usha Chakravarthy ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Thickness Variation ◽  
Age Related

scholarly journals Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yamin Li ◽  
Lina Liang ◽  
Torkel Snellingen ◽  
Kai Xu ◽  
Yun Gao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Case Report Form ◽  
Link Type ◽  
Anti Vegf ◽  
Age Related ◽  
Function Test

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.

Central retinal thickness fluctuations in patients treated with anti-VEGF for neovascular age related macular degeneration

2021 ◽  
pp. 112067212110378
Author(s):  
Francesco Ciucci ◽  
Giuseppina Ioele ◽  
Antonio Bardocci ◽  
Giorgio Lofoco ◽  
Barbara Antonelli ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Thickness ◽  
Treatment Algorithm ◽  
Real Life ◽  
Principal Component ◽  
Age Related Macular Degeneration ◽  
Central Retinal Thickness ◽  
First Year ◽  
Anti Vegf ◽  
Age Related

Purpose: This is a retrospective, single-center, non randomized interventional real life study, investigating the correlation between variability of central retinal thickness (CRT) and functional outcomes during 2 years of anti-VEGF therapy in patients treated for neovascular age related macular degeneration (nAMD). Background: CRT fluctuations can depend on various factors such as the correct timing of injections, the therapeutic algorithm, and the number of injections (NI) performed; it is important to understand if CRT fluctuations are responsible for worse visual outcomes and consequently to identify the correct ways to avoid or reduce them. Methods: Forty-one patients were treated for nAMD with aflibercept: 0.5 mg intravitreal aflibercept was administered every 4 weeks during the first 3 months, then bimonthly over the first year, and after the first year adopting a PRN regimen. Standard deviation of CRT (CRT/SD), BCVA, and NI were recorded. Correlation studies were performed by Pearson’s test, Ancova, and Principal Component Analysis. Results: A negative correlation was found between CRT/SD and final BCVA. In patients who lost more than 15 letters, CRT/SD mean was significantly higher in comparison with patients who lost less than 15 letters. Patients with final BCVA >65 letters showed lower CRT/SD values compared to patients with final BCVA ⩽65 letters. Multivariate analysis confirmed that in patients with higher baseline BCVA, improvement of BCVA was correlated to NI, and lower values of CRT fluctuations were observed. Conclusions: CRT fluctuations, even after an appropriate NI given per year, significantly influence BCVA; a proactive treatment algorithm appears crucial when treating patients with nAMD.

scholarly journals Introduction to the multi-author review on macular degeneration

2020 ◽  
Vol 77 (5) ◽  
pp. 779-780 ◽  
Author(s):  
Anu Kauppinen
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Severe Vision Loss ◽  
Author Review ◽  
Dry Amd ◽  
Endothelial Growth Factor

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.

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