Although there are numerous reports describing an increase in nonocular hemorrhagic events, blood pressure elevation, myocardial infarction, and kidney disease after anti-VEGF therapy,33C36 none of these reports include information regarding the systemic VEGF-A levels. the follow-up. Patients in the treatment groups were older than the healthy controls (= 0.001; the KruskalCWallis test) but did not differ significantly in sex distribution (= 0.870) and BMI (= 0.051). There were no significant differences between the treatment groups in clinical characteristics (Table ?(Table11). Table 1. Demographics and Clinical Baseline Characteristics of Patients 0.05). BMI, body mass index; OD, oculus dexter; OS, oculus sinister; MNV, macular neovascularization; CMT, central macular thickness. Systemic Vascular Endothelial Growth Factor-A Levels A regression analysis adjusted for age, sex, and BMI found no significant difference in the baseline systemic VEGF-A levels between the treatment and control groups (= 0.316; multinominal logistic regression; Table ?Table22 and Figure ?Figure11). Table 2. Systemic Cytokine and CRP Levels 0.05). IQR, interquartile range; BL, baseline; CRP, C-reactive protein. Open in a separate window Fig. 1. Systemic VEGF-A levels before and after RO-9187 IVI of anti-VEGF. Compared with the baseline levels, systemic VEGF-A levels in patients with nAMD decreased significantly on Day 7 (* 0.001) in the aflibercept group and on Day 7 (***= 0.0254) and Day 28 (**** 0.001) in the brolucizumab group. The VEGF-A levels in the aflibercept group at 28 days were significantly higher and significantly lower than those at 7 days postinjection in the brolucizumab group (** 0.001 and *****= 0.0245, respectively). nAMD, neovascular age-related macular degeneration; MDD, minimum detectable dose. In RO-9187 the aflibercept group, the median (interquartile range) systemic VEGF-A levels showed a significant decrease from 12.0 (8.0C18.5) pg/mL to 8.0 (8.0C8.0) pg/mL ( 0.001; Wilcoxon signed-rank test), on Day 7 after the initial IVI, which returned to the baseline level (12.5 [8.5C14.6] pg/mL) (= 0.120) on Day 28. A decrease in systemic VEGF-A levels was observed in 96% (29 of 30) of the patients 7 days after the IVI. In the brolucizumab group, systemic VEGF-A levels significantly decreased from 10.8 (8.0C13.2) pg/mL to 8.0 (8.0C11.5) pg/mL (= 0.0254) on Day 7 after the IVI. The levels remained lower (8.0 [8.0C8.0] pg/mL) than baseline on Day 28 ( 0.001). After the IVI, a decrease in systemic VEGF-A levels was observed in 76% (23 of 30) of the patients on Day 7 and 86% (26 of 30) of those on Day 28. In addition, we observed a decrease in systemic VEGF-A levels from Day 7 to Day 28 (= 0.0245). The brolucizumab group showed significantly lower systemic VEGF-A levels than the aflibercept group 28 RO-9187 days after the IVI ( 0.001, MannCWhitney test). Systemic Vascular Endothelial Growth Factor-B Levels A regression analysis adjusted for age, sex, and BMI revealed no differences in the systemic Met pretreatment levels of VEGF-B between the aflibercept (58.2 [27.8C139.8 pg/mL]) and brolucizumab groups (68.0 [49.9C323.3] pg/mL) compared with the control group (33.7 [12.4C70.2] pg/mL, = 0.295). There were no differences within and across the treatment groups 7 days and 28 days after IVI (Figure ?(Figure22). Open in a separate window Fig. 2. Systemic VEGF-B levels before and after IVI of anti-VEGF. There was no significant difference in within and across group comparison regarding systemic VEGF-B levels in patients with nAMD treated with aflibercept or brolucizumab. There were three outliers 800 pg/mL in the aflibercept group, 11 outliers in the brolucizumab group, and four outliers in the control group that were not illustrated for a better presentation of the figure but are included in the median and interquartile range. nAMD, neovascular age-related macular degeneration; MDD, minimum detectable dose. Systemic Placental Growth Factor Levels In a regression analysis adjusted for age, sex, and BMI, the treatment groups had significantly higher systemic PlGF levels compared with that of the control group (= 0.023, Table ?Table22 and Figure ?Figure3).3). In the aflibercept group, the systemic PlGF levels increased from.
Although there are numerous reports describing an increase in nonocular hemorrhagic events, blood pressure elevation, myocardial infarction, and kidney disease after anti-VEGF therapy,33C36 none of these reports include information regarding the systemic VEGF-A levels