Genetic Polymorphisms Affecting Ranibizumab Response in High Myopia Patients

Abstract

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.

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

“…In this study, we assessed the same cohort of patients published by Blánquez-Martínez et al [ 29 ], including new genetic variants and extending the follow-up period to 12 months.…”

“…As commented in this previous study [ 29 ], we recruited n = 100 patients and n = 113 eyes diagnosed with high myopia and CNV that were treated with ranibizumab. We did not find an adequate DNA concentration for genotyping in one patient ( n = 1 eye).…”

“…In this study, we assessed the same cohort of patients as the previous study by Blánquez-Martínez et al [ 29 ] but with a 12-month follow-up period.…”

“…Specific characteristics about the inclusion/exclusion criteria, considered criteria for high myopia diagnosis, patient management, data management including definitions of BCVA “improvement” and “worsening”, and DNA extraction and genotyping have been previously published in the study by Blánquez-Martínez et al [ 29 ].…”

“…Among our patients, when diagnosed with mCNV and treated with ranibizumab, ARMS2 (rs10490924) and CFH (rs1061170) SNPs were associated with response [ 29 ]. The ARMS2 (rs10490924) G allele and GG genotype led to a better response to ranibizumab at the 6-month follow-up.…”