Neovascular age-related macular degeneration: Intraocular inflammatory cytokines in the poor responder to ranibizumab treatment

Purpose: To determine the levels of interleukin (IL)-6, vascular endothelial growth factor-A, platelet-derived growth factor, placental growth factor (PLGF), and other cytokines in the aqueous fluid of patients with neovascular age-related macular degeneration who respond poorly to ranibizumab. 

Patients and methods: This is an observational, prospective study. Thirty-two eyes from 30 patients were included in the study: 11 patients who responded poorly to ranibizumab and were switched to aflibercept (AF group), 8 patients who received ranibizumab and photodynamic therapy (PDT group), and 13 patients who responded to ranibizumab (control group). Aqueous fluid samples were collected for analysis of cytokine levels at baseline and after 1, 2, and 3 months of treatment. The effect of treatment on cytokine levels was compared between the study groups and between different time points using a linear mixed-effect regression model. 

Results: In the AF group, there was an increase in vascular endothelial growth factor-C, IL-7, and angiopoeitin-2 levels (P=0.01) and a decrease in intercellular adhesion molecule and IL-17 levels (P=0.01) between baseline and 3 months. After adjustment for age, sex, race, and type of lesion at baseline, the PLGF level was higher (P=0.02) and the IL-7 level was lower (P=0.04) in the ranibizumab non-responder group than in the ranibizumab responder group. 

Conclusion: Switching from ranibizumab to aflibercept did not reduce intraocular levels of angiogenesis cytokines, but resulted in improvement of central subfield thickness. PLGF levels were higher in poor responders to ranibizumab. The response of lesions to medication might be related to the stage of choroidal neovascularization. Trial registration: www.ClinicalTrial.gov (NCT02218177c).