A meta-analysis published in the British Journal of Ophthalmology (Br J Ophthalmol 2016;0: 1–9. doi: 10.1136/bjophthalmol-2016-309418), conducted by researchers at the Department of Ophthalmology, Second Affiliated Hospital of Chongqing Medical University, China, suggest that polymorphisms in VEGF related genes may be associated with varying responses to medical treatments for neovascular age related macular degeneration (AMD). Researchers focused on the two most susceptible genes, VEGF-A and VEGFR-2, found that the genetic marker rs833061 on VEGF-A strongly predicts a pooled OR=2.362, indicating that anti-VEGF treatment may be more effective in AMD patients with the rs833061 (CC) genotype.
According to the research group, the study has, “for the first time, summarised the associations of VEGF-related genes with response to anti-VEGF therapy”. The results of the analysis indicated that for the single nucleotide polymorphisms (SNPs) within VEGF-A and VEGFR-2, anti-VEGF treatment was significantly more effective in patients with nAMD having rs833061 (CC vs TT:OR=2.222, 95% CI 1.252 to 3.944, p=0.006; CT vs TT: OR=2.537,95% CI 1.478 to 4.356, p=0.001 and CC vs CT+TT: OR=2.362, 95% CI 1.414 to 3.946, p=0.001), particularly for individuals of Asian descent (CC vs TT: OR=2.903, 95% CI 1.150 to 7.330, p=0.024; CT vs TT: OR=3.849, 95% CI 1.522 to 9.733, p=0.004 and CC vs CT+TT: OR=3.339, 95% CI 1.369 to 8.145, p=0.008, respectively). In addition, the researchers reported that a subgroup analysis demonstrated that rs833061was more likely to be a predictor of response to anti-VEGF therapy specifically when a ranibizumab only treatment regime was in use, or when visual acuity (VA) was employed as a standardized outcome measure.
It has been widely accepted that not all AMD patients respond to anti-VEGF treatments in the same manner and part of the understanding for such an heterogeneous response may be found in the genetic background of patients. While the present study was restricted to components of the VEGF-signalling pathway, it would not be unreasonable to suppose that other pathways that intersect with such signalling may also ameliorate the final drug response. In conclusion, the researchers, commented that, “this is the first systematic review and meta-analysis focused on the association of VEGF-related genes with response to anti-VEGF therapy. Our analysis provides evidence that pharmacogenetics of VEGF-A polymorphisms rs833061 potentially plays a role in the frequency of the positive outcome in anti-VEGF treatment for nAMD, particularly among Asians.”