The Intraocular Cytokine Profile and Therapeutic Response in Persistent Neovascular Age-Related Macular Degeneration

PURPOSE. To investigate the course of inflammatory and angiogenic cytokines in the aqueous humor of patients with persistent/recurrent neovascular age-related macular degeneration (nAMD) under ranibizumab monotherapy (IVM) or ranibizumab plus dexamethasone combination treatment. METHODS. In this 12-month prospective study, 40 eyes with nAMD were treated with either IVM or combined treatment with ranibizumab plus intravitreal dexamethasone implant (IVC). Patients in the IVM group were treated following an as needed'' treatment regimen; patients in the IVC group received ranibizumab and a dexamethasone implant at baseline and were retreated with ranibizumab. At baseline and at each time of retreatment aqueous humor samples were taken. RESULTS. Before treatment, levels of macrophage chemoattractant protein (MCP)-1, monokine induced by c interferon (MIG), and lipocalin-2/neutrophil gelatinase-associated lipocalin (NGAL) were elevated in nAMD patients compared to healthy controls (P = 0.024; P = 0.04; P = 0.01). In contrast, tumor necrosis factor a, IL-12p70, and secreted protein acidic and rich in cysteine (SPARC) concentrations were lower (P = 0.001; P = 0.008; P = 0.03), while vascular endothelial growth factor (VEGF) was not altered (45+/-6/51+/-12 pg/mL nAMD/control group; P = 0.6). During IVC, levels of VEGF, MIG, platelet-derived growth factor (PDGF)-AA, and transforming growth factor beta 1 (P = 0.005; P = 0.011; P = 0.008; P = 0.013) were reduced. Ranibizumab monotherapy did not influence the course of any inflammatory/angiogenic cytokine. Interleukin 6 and PDGF-AA levels correlated with central retinal thickness changes (P = 0.007; P = 0.022). Over the 12-month period visual function was maintained with no significant differences during or between both treatment groups. CONCLUSIONS. Inflammatory proteins are involved in the pathogenesis of chronic macular edema due to AMD and are associated with disease activity. During combined treatment, levels of inflammatory and angiogenic cytokines decreased over a 12-month period with no superiority in functional outcome.