Long-term alterations of systemic vascular endothelial growth factor levels in patients treated with ranibizumab for age-related macular degeneration.

Purpose: To analyze long-term changes of systemic vascular endothelial growth factor (VEGF) levels in patients treated with ranibizumab for neovascular age-related macular degeneration.

Methods: Sixty-one patients with neovascular age-related macular degeneration and 68 age-matched controls were included in the study. Patients were treated with ranibizumab on a pro re nata regimen. Plasma samples were collected before initiation of treatment and after 1 year (30 patients) or 2 years (31 patients) of treatment. Vascular endothelial growth factor was measured by Luminex microbead analysis.

Results: At baseline, patients with neovascular age-related macular degeneration and controls did not differ significantly in VEGF levels (P = 0.062). There was a significant decline in systemic VEGF levels of 39.5% after 1 year (34.2 ± 17.2 pg/mL to 20.7 ± 14.0 pg/mL; P = 7.50 × 10(-5)) and of 46.7% after 2 years (40.4 ± 24.1 pg/mL to 21.5 ± 23.3 pg/mL; P = 2.48 × 10(-4)) of treatment. Patients with persistent activity of choroidal neovascularization showed a significantly smaller decrease of plasma VEGF levels than patients with dry intervals despite the higher number of injections (P = 0.048).

Conclusion: In addition to immediate effects limited to days if not hours, ranibizumab also leads to long-term alterations of systemic VEGF to subnormal levels. Patients with persistent choroidal neovascularization activity showed a less pronounced VEGF decrease. Therefore, VEGF levels might be a useful marker for treatment response.