Common Variant in VEGFA and Response to Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration
2013
Age-related macular degeneration (AMD) is a leading cause of visual impairment in aging
populations in industrialized countries. Here we investigated whether the genotype of vascular endothelial
growth factor A (VEGFA) gene is associated with response to anti-VEGF therapy. 223 eyes with neovascular
AMD were treated with intravitreal anti-VEGF therapy. Responders were defined as patients who had an
improvement in best corrected visual acuity (BCVA) of at least 5 letters or one line on the EDTRS visual acuity
chart along with resolution of intraretinal or subretinal fluid over 12 months. Patients who did not meet the
definition of responders were classified as poor-responders. The vision of responders (n = 148) improved while
the vision of poor-responders (n = 75) worsened (P <0.001). Responders on average had a decrease in central
foveal thickness (CFT), while poor-responders had an increase in CFT (P <0.001). Compared with the
responder group, the poor-responder group had a higher frequency of the risk (T) allele (Allelic P = 0.019) and
TT genotype (P = 0.002 under a recessive model) for the VEGFA-rs943080 polymorphism. VEGFA expression
was 1.8-fold higher in cells with the VEGFA rs943080 TT genotype than in cells with the VEGFA rs943080 CC
genotype (P = 0.012). Age, gender, smoking, diabetes mellitus, and hypertension did not play a significant role
in treatment response, but BMI was found to be significantly different between responders and poorresponders
(P = 0.033). In conclusion, we demonstrated a potential pharmacogenetic relationship between the
VEGFA gene and treatment response to anti-VEGF therapy.
The studies are registered at ClinicalTrials.gov under the identifiers NCT00474695 (http://clinicaltrials.
gov/ct2/show/NCT00474695) and NCT01464723 (http://clinicaltrials.gov/ct2/show/NCT01464723).
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