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Randomized Controlled Trial
, 38 (9), 1801-1808

CHANGES IN PLASMA VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AFTER INTRAVITREAL INJECTION OF BEVACIZUMAB, AFLIBERCEPT, OR RANIBIZUMAB FOR DIABETIC MACULAR EDEMA

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Randomized Controlled Trial

CHANGES IN PLASMA VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AFTER INTRAVITREAL INJECTION OF BEVACIZUMAB, AFLIBERCEPT, OR RANIBIZUMAB FOR DIABETIC MACULAR EDEMA

Takao Hirano et al. Retina.

Abstract

Purpose: The aim of this study was to investigate the changes in plasma vascular endothelial growth factor (VEGF) level depending on the severity of diabetic retinopathy (DR) or diabetic macular edema (DME) and after intravitreal injection of bevacizumab, aflibercept, or ranibizumab for treatment of DME.

Methods: Plasma VEGF level was evaluated in 72 patients with DR and changes were measured in 42 patients with DME receiving intravitreal injections of bevacizumab, aflibercept, or ranibizumab at the initial injection.

Results: There were no correlations between plasma VEGF level and the severity of DME or DR. Baseline plasma VEGF level (51.9 pg/mL) was significantly reduced using bevacizumab to 11.9 pg/mL after 1 week and 24.1 pg/mL after 4 weeks (P = 0.0130 and 0.0201, respectively). In aflibercept-treated eyes, plasma VEGF decreased from 52.2 pg/mL to 7.8 pg/mL and 12.6 pg/mL, respectively, at the same time points (both P < 0.001). No such reductions were observed in patients receiving ranibizumab.

Conclusion: Baseline plasma VEGF level showed no correlations with DR or DME severity, whereas intravitreal injection of bevacizumab or aflibercept significantly reduced plasma VEGF for up to 4 weeks and ranibizumab produced no such effects. Changes in plasma VEGF level seemed not to be critical in progression or treatment of DME and DR.

Conflict of interest statement

None of the authors has any financial/conflicting interests to disclose.

Figures

Fig. 1.
Fig. 1.
Plasma VEGF level in patients with DME and nondiabetic age-matched control subjects. There was no significant difference between mean values in patients with DME (56.5 ± 47.7 pg/mL) and controls (51.7 ± 31.1 pg/mL) (P = 0.9238). N.S., not significant.
Fig. 2.
Fig. 2.
Correlation between the severity of DR and plasma VEGF concentration. Plasma VEGF showed no statistically significant correlation with DR stage advancement for mild NPDR (66.3 ± 36.9 pg/mL), moderate NPDR (52.3 ± 45.2 pg/mL), severe NPDR (51.7 ± 47.4 pg/mL), or PDR (72.0 ± 55.0 pg/mL) (r = 0.1200, P = 0.3152).
Fig. 3.
Fig. 3.
Correlation between the severity of DME and plasma VEGF concentration. Plasma VEGF level did not show any statistically significant correlation with DME severity for mild DME (46.9 ± 29.7 pg/mL), moderate DME (44.3 ± 25.3 pg/mL), or severe DME (62.8 ± 55.2 pg/mL) (r = 0.1401, P = 0.2405).
Fig. 4.
Fig. 4.
Changes in vision and CMT after a single intravitreal anti-VEGF agent injection. In the IVB, IVA, and IVR groups, vision was not improved significantly at 1 week and reached statistically significant amelioration in the IVA group only at 4 weeks. In all test groups, CMT showed a significant reduction at 1 week. The IVA and IVR groups retained this reduction at 4 weeks. *P < 0.05, **P < 0.01, ***P < 0.001. N.S., not significant.
Fig. 5.
Fig. 5.
Plasma VEGF levels after a single injection of IVB, IVA, or IVR in patients with DME. Intravitreal bevacizumab and IVA induced significant suppression of plasma VEGF at 1 and 4 weeks after injection. Mean plasma VEGF after IVR was largely unchanged. *P < 0.05, ***P < 0.001. N.S., not significant.

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