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.

High myopia is an ophthalmic pathology that affects half of the young adults in the United States and Europe and it is predicted that a third of the world’s population could be nearsighted at the end of this decade. It is characterized by at least 6 diopters or axial length > 26 mm and, choroidal neovascularization (CNV) in 5 to 11% of cases. Ranibizumab is a recombinant humanized monoclonal antibody fragment. It is an anti-vascular endothelial growth factor (anti-VEGF) drug used in the treatment of CNV. Many genetic polymorphisms have been associated with interindividual differences in the response to ranibizumab, but these associations were not yet assessed among patients with high myopia and CNV. We performed a retrospective study assessing the association of genetic polymorphisms with response to ranibizumab in patients with CNV secondary to high myopia (mCNV). We included genetic polymorphisms previously associated with the response to drugs used in CNV patients (bevacizumab, ranibizumab, aflibercept, and photodynamic therapy (PDT)). We also included genetic variants in the VEGFA gene. Based on our results, ARMS2 (rs10490924) and CFH (rs1061170) are associated with response to ranibizumab in high myopia patients; and, included VEGFA genetic polymorphisms are not associated with ranibizumab response in our population but might be related to a higher risk of CNV.

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