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

Abstract

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.

Determination of Vascular Endothelial Growth Factor-B Concentrations in Aqueous Humor and Plasma of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy Patients Before and After Anti-VEGF Therapy

“…At the same time, the CRT had significantly statistical difference between the nAMD group and PCV group at baseline, and the CRT in nAMD remained thinner than in PCV after treatment; thus, we hypothesized that CRT might help to distinguish PCV from nAMD. Our study proved that BCVA improvement was strongly correlated with CRT reduction in the nAMD group rather than in PCV group; therefore, nAMD and PCV might have different drug responses to anti-VEGF therapy in accordance with previous studies [35,36]. Moreover, we analyzed the correlation between BCVA as well as CRT and VEGF-B levels before and after anti-VEGF treatment, but failed to find strong correlations.…”

Genetic Polymorphisms in VEGFR Coding Genes (FLT1/KDR) on Ranibizumab Response in High Myopia and Choroidal Neovascularization Patients

“…Polypoidal choroidal neovascularization is usually considered a sub-type of CNV. In patients with CNV and/or PCV, VEGFA (rs2010963) [ 43 ], HTRA1 (rs11200638) [ 44 ], and especially CFH (rs1061170) and ARMS2 (rs10490924) [ 45 ] were also found to be associated with ranibizumab efficacy.…”

Genetic Polymorphisms Affecting Ranibizumab Response in High Myopia Patients

“…The sample size calculation was based on previous research articles evaluating the influence of considered genetic polymorphisms on ranibizumab response on patients with other pathologies [27][28][29][30][31][32][33]. Furthermore, we recruited the total number of patients with high myopia and treated them with ranibizumab in our hospital for five years.…”

“…Also, many genetic polymorphisms in the VEGFA gene were associated with interindividual differences in the responses to anti-VEGFA drugs or PDT among AMD patients [27,29,32]. Among CNV and/or polypoidal choroidal vasculopathy patients, usually considered a subtype of CNV, also there are SNPs associated with variable response to ranibizumab, bevacizumab or PDT as HTRA1-625 A/G (rs11200638), F13A1 (rs5985) CFH I62V (rs800292), CFH Y402H (rs1061170) and, especially, ARMS2 A69S (rs10490924) [33]. As we can see, no studies have assessed the association of genetic variants with interindividual differences in the responses to ranibizumab among high myopia patients despite ranibizumab being commonly used to treat this pathology.…”