Genetic predictive biomarkers of anti-VEGF treatment response in patients with neovascular age-related macular degeneration

2015 ◽  
Vol 60 (2) ◽  
pp. 138-152 ◽  
Author(s):  
Sascha Fauser ◽  
George N. Lambrou
Keyword(s):  
Macular Degeneration ◽  
Treatment Response ◽  
Predictive Biomarkers ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related

scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration

2014 ◽  
Vol 59 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert P. Finger ◽  
Sanjeewa S. Wickremasinghe ◽  
Paul N. Baird ◽  
Robyn H. Guymer
Keyword(s):  
Macular Degeneration ◽  
Treatment Response ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related

scholarly journals Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Miltiadis K. Tsilimbaris ◽  
Maria I. López-Gálvez ◽  
Roberto Gallego-Pinazo ◽  
Philippe Margaron ◽  
George N. Lambrou
Keyword(s):  
Treatment Outcomes ◽  
Treatment Response ◽  
Disease Duration ◽  
Case Reports ◽  
Predictive Biomarkers ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Pubmed Database ◽  
Baseline Characteristics

Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response.Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology.Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review.Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

CFH Y402H and VEGF Polymorphisms and Anti-VEGF Treatment Response in Exudative Age-Related Macular Degeneration

2016 ◽  
Vol 56 (3) ◽  
pp. 132-138 ◽  
Author(s):  
Burcin Kepez Yildiz ◽  
Sengul Ozdek ◽  
Mehmet Ali Ergun ◽  
Sezen Ergun ◽  
Fulya Yaylacioglu Tuncay ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Treatment Response ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Polymorphisms

scholarly journals Predictive Biomarkers of Age-Related Macular Degeneration Response to Anti-VEGF Treatment

2021 ◽  
Vol 11 (12) ◽  
pp. 1329
Author(s):  
Ana I. Oca ◽  
Álvaro Pérez-Sala ◽  
Ana Pariente ◽  
Rodrigo Ochoa ◽  
Sara Velilla ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Mononuclear Cells ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Age Related Macular Degeneration ◽  
Classification Model ◽  
Patient Specific ◽  
Anti Vegf ◽  
Age Related ◽  
Number Of Patients

Age-related macular degeneration (AMD) is an incurable disease associated with aging that destroys sharp and central vision. Increasing evidence implicates both systemic and local inflammation in the pathogenesis of AMD. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is currently the first-line therapy for choroidal neovascularization in AMD patients. However, a high number of patients do not show satisfactory responses to anti-VEGF treatment after three injections. Predictive treatment response models are one of the most powerful tools for personalized medicine. Therefore, the application of these models is very helpful to predict the optimal treatment for an early application on each patient. We analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) from AMD patients before treatment to identify biomarkers of response to ranibizumab. A classification model comprised of four mRNAs and one miRNA isolated from PBMCs was able to predict the response to ranibizumab with high accuracy (Area Under the Curve of the Receiver Operating Characteristic curve = 0.968), before treatment. We consider that our classification model, based on mRNA and miRNA from PBMCs allows a robust prediction of patients with insufficient response to anti-VEGF treatment. In addition, it could be used in combination with other methods, such as specific baseline characteristics, to identify patients with poor response to anti-VEGF treatment to establish patient-specific treatment plans at the first visit.

scholarly journals Meta-analysis of the pharmacogenetics of ARMS2 A69S polymorphism and the response to advanced age-related macular degeneration

2019 ◽  
Author(s):  
Jun Zhang ◽  
Zhaohui Liu ◽  
Shuqiong Hu ◽  
Jian Qi
Keyword(s):  
Macular Degeneration ◽  
Treatment Response ◽  
Meta Analysis ◽  
East Asian ◽  
Age Related Macular Degeneration ◽  
Large Sample Size ◽  
Clinical Prognosis ◽  
Anti Vegf ◽  
Age Related ◽  
Arms2 A69s

Abstract Background Age-related macular degeneration (AMD) causes irreversible vision loss, and targeted anti-vascular endothelial growth factor (VEGF) therapy is now the most common and effective treatment. The aim of this meta-analysis is to discuss whether genetic polymorphism of ARMS2 A69S could confer susceptibility to advanced AMD with the response to anti-VEGF treatment.Methods We performed a meta-analysis of relevant published studies selected through electronic databases. A total of 21 preferred studies regarding the association between ARMS2 gene and anti-VEGF treatment response in advanced AMD were generally included in the meta-analysis.Results The pooled results demonstrated that the carriage of G allele for ARMS2 A69S presented a better clinical prognosis for advanced AMD treated with anti-VEGF drugs (OR=1.38, 95% CI=1.13-1.69, P=0.002). Additionally, in the subgroup analysis based on ethnicity, ARMS2 polymorphisms were more likely to be a positive responder for East Asian patients (OR=1.67, 95% CI=1.29-2.16, P<0.001).Conclusion This meta-analysis through a series of rigorous methodology data demonstrated a significant association between ARMS2 A69S polymorphism and the anti-VEGF treatment response in advanced AMD, especially among East Asian population. Numerous well-designed, randomized, multicenter clinical trials with large sample size are required to validate the association.

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