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Aaron Y. Lee, Gokul N. Kumar, Melissa P. Osborn, Milam A. Brantley, Jr.; The Pharmacogenetic Effect Of VEGF-A On Neovascular Amd Patients Treated With Anti-VEGF Therapy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3324.
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To determine if single nucleotide polymorphisms (SNPs) in Vascular Endothelial Growth Factor A (VEGF-A) are associated with more frequent reinjections in neovascular Age-related Macular Degeneration (AMD) patients treated with anti-VEGF therapy.
A retrospective chart review was performed to identify the first treated eye of AMD patients receiving intravitreal ranibizumab or bevacizumab injections on a PRN regimen with at least 4 months of follow-up. DNA was collected by buccal mouthwash, purified, and genotyped by Sequenom. Nine SNPs were chosen by tagged-based approach to cover the VEGF-A gene. Recurrent events were defined as injections performed within the PRN period, after the first 90 days of the first injection. Significance analysis of microarray (SAM) approach was used to test the stratified, recurrent event Cox-regression coefficient of all SNPs together against a global null hypothesis with one million random permutations. A delta of 0.05 was used as a threshold of significance and SNPs higher than this threshold were used for further analysis.
A total of 186 patients (186 eyes) met study inclusion criteria. The mean age was 79.1 years, and 71% were females. Median follow-up was 44.3 months (25th and 75th percentile were 25.4 and 51.0 months respectively). By SAM, one SNP, rs3025035, was significantly higher than the delta threshold (Figure 1). For rs3025035, the calculated Cox proportional hazard ratio was 0.819 (95% confidence intervals: 0.684 to 0.981, p = 0.030 by Wald score).
Genetic variations in rs3025035 in the intronic region of VEGF-A may have a modest protective effect on the need for retreatment by anti-VEGF therapy in neovascular AMD patients.
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