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 DR and the response to 1 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 intravitreal 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 [1.25-3.490, 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. The rs12366035*T/T genotype showed the worst pretreatment 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 +/- 35.43 mu in G/G vs. 3.57 +/- 8.74 mu 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.