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Farshad Abedi, Sanj Wickremasinghe, Andrea J. Richardson, Lucy Busija, Paul Baird, Robyn Guymer; Do VEGF Gene Variants Contribute To The Treatment Outcomes Of Intravitreal Anti-VEGF Treatment In Patients With Neovascular Age-related Macular Degeneration?. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3067. doi: https://doi.org/.
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Anti-Vascular Endothelial Growth Factor (anti-VEGF) treatment has revolutionised the treatment of choroidal neovascularisation (CNV) associated with AMD. Yet not everyone gains vision and around 10% continue to lose vision despite treatment. Factors that contribute to treatment outcome are incompletely understood. In the current study we examine the possible role of VEGF gene variants in determining the visual outcome with anti-VEGF treatments.
Two hundred and sixty patients (age range 58 - 94 years, mean age: 79), receiving anti-VEGF treatment for CNV secondary to AMD, were prospectively monitored over a 12-month period. Information relating to the demographics, lesion characteristics, visual acuity and number of injections was collected. VEGFA gene was tagged using the International HapMAP Project. Seven tSNPs (Rs3024994, Rs3025000, Rs3025030, Rs3025035, Rs3025047, Rs3025010, and Rs 3025042) were selected using the pairwise algorithm and a CEU (Caucasian) population. A strong linkage disequilibrium (LD) tagging criteria of r2 >0.8 was used and all SNPs had a minor allele frequency (MAF) of at least 0.05. Genotyping of SNPs was undertaken using the MassARRAY® platform.
Of the 260 patients recruited, 216 have completed 12 months follow up. 29.6% gained, 63% maintained and 7.4% lost vision after three months. These proportions were 24.2%, 55.2% and 20.6%- respectively, after 12 months. Mean number of injections was 6 (SD: 2.5) after 12 months. Variant genotype distributions of each of the seven SNPs were determined (e.g. Rs3025035 consisted of CC: 86%, CT: 12.9% and TT: 0.5%, compared to CC: 81.7%, CT: 16.7% and TT: 1.7% for the normal population in the NCBI database). Chi-squared analysis of the data did not reveal any statistically significant relationship between the different variants of any of the 7 VEGFA SNPs and the treatment outcomes.
To date we have not found any significant association between any of the VEGFA SNPs and the treatment outcome. Multivariate data analysis will be used to further investigate the possible role of combinations of the different SNPs after the remaining patients complete one year follow up in February 2011. If the VEGF gene variants do influence treatment outcomes, it may be through different VEGF levels in the vitreous and could indicate that treatment regimens need to be individualized according to genotype.
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