Intraocular and systemic inflammation-related cytokines during one year of ranibizumab treatment for neovascular age-related macular degeneration

Purpose: To determine inflammation-related intraocular and systemic cytokine concentrations in neovascular age-related macular degeneration (nAMD) compared with controls and to assess the influence of long-term intravitreal ranibizumab treatment over 1 year. Methods: Aqueous humour and blood plasma of 21 controls and 17 treatment-naive nAMD patients were collected prior to cataract surgery or ranibizumab treatment. Follow-up specimens in nAMD patients were acquired immediately prior to subsequent ranibizumab injections as needed. Multiplex bead assays were conducted for ten inflammation-related cytokines and vascular endothelial growth factor (VEGF). p-values were Holm-Bonferroni-corrected for multiple comparisons. Results: Prior to ranibizumab treatment, initiation aqueous humour levels of monocyte chemo-attractant protein (MCP)-1/CCL2 (p = 0.005) and vascular cell adhesin molecule (VCAM) (p = 0.002) were elevated in nAMD compared with controls. Other intraocular cytokines did not differ, including VEGF. In plasma, no differences between nAMD patients and controls were found at baseline. Pro re nata ranibizumab treatment over 12 months with 8 +/- 2 injections reduced aqueous VEGF (p < 0.0001) with a trend to reduced VEGF plasma concentrations (p = 0.046), with all specimens taken at least 28 days after the previous injection. All other local and systemic cytokines remained unchanged. Conclusion: Neovascular age-related macular degeneration is associated with local ocular MCP-1/CCL2 and VCAM elevations, suggesting a local inflammatory involvement in the pathophysiology of nAMD. We did not detect systemic differences. Ranibizumab treatment does not result in local or systemic changes of these cytokines, in contrast to VEGF suppression. MCP-1/CCL2 and VCAM may be potential additional treatment targets for nAMD.