Changes in Systemic Levels of Vascular Endothelial Growth Factor After Intravitreal Injection of Aflibercept or Brolucizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE To analyze and compare the effects of intravitreal brolucizumab vs. aflibercept on systemic vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration. METHODS In this prospective interventional case series study, brolucizumab (6.0 mg/50 µL) or aflibercept (2.0 mg/50 µL) was injected intravitreally in 30 patients each. Blood samples were drawn at baseline and 7 and 28 days after the first injection. Systemic VEGF-A levels were measured using enzyme-linked immunosorbent assay. Thirty healthy individuals served as controls. RESULTS The median baseline systemic VEGF-A levels in the brolucizumab, aflibercept, and control groups were 10.8 (8.0-13.2), 12.0 (8.0-18.5), and 10.0 (8.0-15.1) pg/ml, respectively (p=0.315). In the brolucizumab group, VEGF-A levels significantly decreased to 8.0 (8.0-11.5) pg/ml on day 7 (p=0.0254) and to 8.0 (8.0-8.0) pg/ml on day 28 (p<0.001). In the aflibercept group, VEGF-A levels significantly decreased to 8.0 (8.0-8.0) pg/ml on day 7 (p<0.001) but returned to baseline level, 12.5 (8.5-14.6) pg/ml, on day 28 (p=0.120). VEGF-A levels were significantly different between the treatment groups after 28 days (p<0.001). CONCLUSION Intravitreal brolucizumab resulted in a sustained reduction of systemic VEGF-A levels until 28 days post-treatment, which raises concerns regarding its safety and long-term effects.