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.

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.

scholarly journals Efficacy Comparison of Intravitreal Anti-VEGF Therapy for Three Subtypes of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jianqing Li ◽  
Jiayi Xu ◽  
Yiyi Chen ◽  
Jiaju Zhang ◽  
Yihong Cao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Macular Degeneration ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Cochrane Library ◽  
Anti Vegf ◽  
Age Related ◽  
Significant Difference ◽  
The Mean

Purpose. Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy has been widely used for the treatment of neovascularization (NV) secondary to age-related macular degeneration (AMD). This study aimed to compare the efficacy among different subtypes of neovascular age-related macular degeneration (nAMD). Methods. PubMed, Embase, and the Cochrane Library were searched for eligible studies. We performed meta-analysis using Review Manager 5.3 and Stata/SE 12.0. Results. A total of 24 studies met our inclusion criteria and were included in the systematic review. At 3 months, the mean logarithm of the minimum angle of resolution (logMAR) improvements were −0.09, −0.18, and −0.23 for type 1, 2, and 3, respectively, while the mean macular thickness (MT) changes were −104.83, −130.76, and −196.29 μm. At 12 months, the mean changes in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters were 6.38, 8.12, and 9.37, while the MT decrease was 126.51, 126.52, and 139.85 μm, respectively. However, statistically significant difference was only found between type 1 and 3 in vision improvement, both in the short term (p=0.0002) and long term (p=0.01). Conclusions. The reactivity to VEGF inhibitors varied among different subtypes of nAMD. The efficacy of intravitreal anti-VEGF therapy in type 3 nAMD was statistically better than type 1 when considering vision improvement at 3 and 12 months. Thus, the lesion subtype is a predictor for the treatment outcome which can help guide prognosis.

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 Clinical efficacy of intravitreal corticoid as an adjunctive therapy to anti-VEGF treatment of neovascular age-related macular degeneration: a Meta-analysis

2021 ◽  
Vol 14 (7) ◽  
pp. 1092-1099
Author(s):  
Bo-Hao Cui ◽  
◽  
Wen-Wen Wang ◽  
Hao Yang ◽  
Ya-Lan Dong ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Adjunctive Therapy ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Cochrane Library ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Time Point

AIM: To evaluate the efficacy and safety of intravitreal corticoid as an adjunctive therapy to anti-vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (nvAMD). METHODS: Four databases including PubMed, Embase, Cochrane Library, and the clinicaltrials.gov were comprehensively searched for studies comparing intravitreal corticoid plus anti-VEGF (IVC/IVA) vs anti-VEGF monotherapy (IVA) in patients with nvAMD. GRADE profiler was used to assess the quality of outcomes. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events including the occurrence of severe elevation of intraocular pressure (IOP) and the progress of cataract were extracted from the eligible studies. Review Manager (RevMan) 5.3 was used to analyze the data. RESULTS: There was no statistic difference of mean change in BCVA at 6 and 12mo between IVC/IVA and IVA group [95% confidence interval (CI): -2.28 to 4.24, P=0.55; 95%CI: -3.01 to 8.70, P=0.34]. No statistic difference was found in the change of CMT between two groups at 6mo time point (95%CI: -17.98 to 16.42, P=0.93) while the CMT reduction in IVC/IVA group was significantly more obvious than IVA group at 12mo time point [mean difference (MD)=-44.08, 95%CI: -80.52 to -7.63, P=0.02]. The risk of occurrence of severe elevation of IOP in the IVC/IVA group was higher than that in the IVA group (95%CI: 1.92 to 9.48; P=0.0004). Cataract progression risk was calculated no statistic difference between two groups (95%CI: 0.74 to 4.66; P=0.18). CONCLUSION: No visual or anatomical benefits are observed in IVC/IVA group at 6mo. At 12mo, the CMT of the IVC/IVA group is significantly lower than that of the IVA group. Risk of severe elevation of IOP is significantly higher when treated by IVC/IVA.

scholarly journals Genetic Variants Affecting Anti-VEGF Drug Response in Polypoidal Choroidal Vasculopathy Patients: A Systematic Review and Meta-Analysis

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1335
Author(s):  
Xando Díaz-Villamarín ◽  
David Blánquez-Martínez ◽  
Ana Pozo-Agundo ◽  
Ana María Pérez-Gutiérrez ◽  
José Ignacio Muñoz-Ávila ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Response ◽  
Genetic Variants ◽  
Polypoidal Choroidal Vasculopathy ◽  
Drug Response ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Arms2 A69s ◽  
Choroidal Vasculopathy

Polypoidal choroidal vasculopathy (PCV) is usually regarded as a subtype of choroidal neovascularization (CNV) that is secondary to age-related macular degeneration (AMD) characterized by choroidal vessel branching, ending in polypoidal lesions. Despite their close association, PCV and neovascular AMD have shown differences, especially regarding patients’ treatment response. Currently, antivascular endothelial growth factor (anti-VEGF) drugs, such as ranibizumab, bevacizumab and aflibercept, have demonstrated their efficacy in CNV patients. However, in PCV, anti-VEGF treatments have shown inconclusive results. Many genetic polymorphisms have been associated with a variable response in exudative/wet AMD patients. Thus, the aim of this study is to explore the genetic variants affecting anti-VEGF drug response in PCV patients. In this regard, we performed a systematic review and meta-analysis. We found four variants (CFH I62V, CFH Y402H, ARMS2 A69S, and HTRA1-62A/G) that have been significantly related to response. Among them, the ARMS2 A69S variant is assessed in our meta-analysis. In conclusion, in order to implement anti-VEGF pharmacogenetics in clinical routines, further studies should be performed, distinguishing physio-pathogenic circumstances between PCV and exudative AMD and the combined effect on treatment response of different genetic variants.

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