Abstract
Purpose:
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.
Methods:
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.
Results:
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).
Conclusions:
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.