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Claus Zehetner, Martina T Kralinger, Martin Stattin, Rudolf Kirchmair, Nikolaos Bechrakis, Gerhard Kieselbach; Systemic Counterregulatory Response of Placental Growth Factor Levels to Intravitreal Aflibercept Therapy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4596.
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© ARVO (1962-2015); The Authors (2016-present)
Data analyzing the systemic pharmacodynamic effects on PlGF, which is targeted by aflibercept, in patients with neovascular AMD are lacking. We performed a prospective, observational clinical study to analyze the plasma levels of VEGF-A, VEGF-B and PlGF after intravitreal injections of aflibercept, ranibizumab and bevacizumab.
19 patients were treated with intravitreal aflibercept, 19 with ranibizumab, and 18 with bevacizumab. The cytokine levels were measured by ELISA just before the injection, after 7 days and 1 month. Controls were established from healthy 22 age- and sex-matched participants.
There were no significant differences between the aflibercept, ranibizumab, bevacizumab and the control cohort with respect to demography and the pretreatment plasma levels of VEGF-A, VEGF-B, and PlGF. After intravitreal injection of aflibercept plasma VEGF-A measurements were significantly reduced to a median of <9 pg/ml after 7 days (p < 0.001) and to 17.0 [8.0-25.0] after weeks (p < 0.001). A reduction of systemic VEGF-A levels could also be observed after intravitreal bevacizumab injections with a median VEGF-A of 17.5 [10.3-27.5] pg/ml after 1 week (p < 0.001) and 17.0 [10.5-31.5] pg/ml after 4 weeks. (p < 0.001). No significant effects on systemic VEGF-A could be observed in those treated with intravitreal ranibizumab<br /> No significant effects on systemic VEGF-B and could be observed after intravitreal anti-VEGF injections in any of the three treatment groups.<br /> One week after intravitreal aflibercept injection a significant systemic upregulation of PlGF could be observed with a median PLGF measurement of 38.0 [31.0-44.0] pg/ml (p<0.001). The increase of PlGF compared to baseline occurred in all patients treated with aflibercept (19 out of 19 patients; 100%) After 4 weeks the PlGF levels remained significantly elevated compared to pretreatment measurements with a median PlGF of 16.0 [11.0-19.0] pg/ml (p=0.005).
In this study we report a significant systemic upregulation of the pro-angiogenic cytokine PlGF after intravitreal application of aflibercept. This could represent a host counterregulatory response to antiangiogenic therapy with intravitreal aflibercept.
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