Abstract

BackgroundTo evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME).MethodsThis prospective case-control study included a total of 50 participants assigned to one of three groups, including 10 individuals with DME and non-proliferative diabetic retinopathy (NPDR), 13 with DME, and proliferative diabetic retinopathy (PDR), and 27 healthy individuals as a control group. Serum VEGF and netrin-1 concentrations were measured by enzyme-linked immunosorbent assays (ELISAs) immediately before, as well as 1 week and 1 month after, intravitreal BCZ injection.ResultsThe mean VEGF serum concentrations in the PDR and NPDR groups were 388.4 and 196.9 pg/mL at baseline, respectively. After 1 week, these concentrations changed to 193.41 and 150.23 pg/mL, respectively (P = 0.001 and P = 0.005, respectively); after 1 month, the concentrations were 97.89 and 76.46 pg/mL, respectively (P = 0.001 and P = 0.009, respectively). The mean netrin-1 serum concentrations in the PDR patients and NPDR groups were 318.2 and 252.7 pg/mL at baseline, respectively. After 1 week, these concentrations increased to 476.6 and 416.3 pg/mL, respectively (P = 0.033 and P = 0.005, respectively), and after 1 month, they were 676.6 and 747.5 pg/mL, respectively (P = 0.001 and P = 0.005, respectively). The correlation analysis revealed a significant inverse relationship between changes in serum VEGF and netrin-1 concentrations in both the PDR and NPDR groups (r = − 0.685, P = 0.029).ConclusionsIntravitreal BCZ injections work systemically to significantly decrease serum VEGF levels, leading to a significant upregulation in the concentration of another angiogenic mediator, netrin-1.

Highlights

  • To evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME)

  • There were no significant differences among the three groups in terms of age, sex, and level of hypertension (HT), there was a significant difference between the groups in terms of baseline serum concentrations of netrin-1 and VEGF (Tables 1 and 2)

  • Baseline LogMAR and cube average thickness (CAT) values showed no significant differences between the non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) groups. (p = 0.648, p = 0.208, respectively)

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Summary

Introduction

To evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME). Diabetic macular edema (DME) occurs as a result of fluid leakage from abnormal perifoveal retinal capillaries or microaneurysms into the intraretinal and subretinal areas. The pathogenesis of DME is multifactorial, and it is accompanied by the destruction of both the blood-retinal barrier (BRB) and the blood-aqueous barrier. Several studies have detected elevated vascular endothelial growth factor (VEGF) and pro-inflammatory cytokine concentrations in the aqueous humor of DME patients, as well as an increase in the concentrations of netrin-1 [1, 2]. Yu et al detected increased BRB breakdown in diabetic rats after intravitreal (0.1 μg/mL) netrin-1 injection [5]

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