. Purpose:  To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age‐related macular degeneration (AMD). Methods:  Forty‐three patients with exudative AMD and 19 age‐ and sex‐matched control patients without chorioretinal diseases were studied. Nineteen patients were treated with intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood samples were collected just before the first injection, and 28 days after three initial consecutive injections performed in 4‐weekly intervals (loading dose). Concentration of VEGF in the plasma was measured by ELISA. Results:  At baseline, the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma concentrations in patients with wet AMD were comparable to controls (p = 0.225). Twenty‐eight days after the third injection, a significant reduction of 42% in the median VEGF plasma levels was found in bevacizumab‐treated patients (109.97 pg/ml; p = 0.0002) but not in ranibizumab‐treated patients (189.97 pg/ml; p = 0.198) where a reduction of 0.7% in the median value was found. Conclusions:  Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days after intravitreal injection in patients with exudative AMD. Ranibizumab did not achieve a significant plasma VEGF reduction at the same time‐point. These findings alert to the potential systemic safety differences between the two drugs after intravitreal administration.

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A greater number of intravitreal anti-vascular endothelial growth factor injections is associated with an increased risk for sustained IOP elevation in eyes with neovascular age-related macular degeneration receiving intravitreal ranbizumab and/or bevacizumab.