Association of VEGF gene family variants with central macular thickness and visual acuity after Aflibercept short-term treatment in diabetic patients: A pilot study.

INTRODUCTION Diabetic Retinopathy (DR) is one of the major vision-threatening causes worldwide. Searching for an individualized therapeutic strategy to prevent its progress is challenging. OBJECTIVE This work aimed to investigate the association of angiogenesis-inducer vascular endothelial growth factor (VEGF) gene family and related receptor variants (rs833069, rs12366035, rs7664413, rs7993418, and rs2305948) with susceptibility of diabetic retinopathy (DR) and the response to one dose of aflibercept treatment in type 2 diabetes mellitus (T2DM). METHODS Consecutive eligible patients with T2DM (n=125) and 110 unrelated controls were enrolled in this preliminary prospective case-controlled study. Genotyping was identified using TaqMan Real-Time PCR. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with the clinical/ophthalmological characteristics and early response to intravitreous aflibercept treatment in terms of improved visual acuity (BCVA) and central macular thickness (CMT). RESULTS We found that both VEGFB rs12366035 and VEGFC rs7664413 conferred higher risk for DR progression under [allelic: OR (95%CI); 1.71 (1.07-2.74), homozygote comparison: 3.55 (1.32-9.57), and recessive: 3.77 (1.43-9.93) models] for the former, and under [allelic: 2.09 (1.25-3.49), homozygote comparison: 2.76 (1.02-7.45), and recessive: 2.62 (0.98-6.98) models] for the latter. In contrast, VEGFR1 rs7993418 conferred protection against DR under heterozygote comparison and dominant models. rs12366035*T/T genotype showed the worst pre-treatment BCVA score (0.35±0.24) compared to other corresponding genotypes (0.66±0.26 in C/T and 0.54±0.25 in C/C carriers) (p = 0.008). Meanwhile, patients with rs7993418*G/G of VEGFR1 exhibited a significant reduction in CMT after aflibercept injection (12.26±35.43µ in G/G versus 3.57±8.74µ in A/A) (p = 0.037). CONCLUSIONS polymorphisms of the studied VEGF/receptors could be considered as genetic risk factors of DM/DR development and could play an important role in aflibercept early response for DR patients in the study population.