Changes in Aqueous Humor Cytokine Profile Following Intravitreal Brolucizumab Injection

Intravitreal brolucizumab, approved for neovascular age-related macular degeneration (nAMD), may trigger immune responses leading to intraocular inflammation (IOI) by increasing pro-inflammatory cytokines. This study evaluates cytokine levels in the aqueous humor of patients before and after intravitreal brolucizumab injection.

Fourteen eyes of fourteen participants with nAMD or polypoidal choroidal vasculopathy (PCV) and who received intravitreal brolucizumab injection were included. Aqueous humor was collected before and 1 month following the injection. The aqueous cytokine profile was analyzed using a bead-based multiplex immunoassay. Paired t-test and Wilcoxon-signed rank test were used to analyze the results.

Ten eyes were diagnosed with PCV, and four were nAMD. The aqueous IL-8 and IL-22 levels were significantly increased after intravitreal brolucizumab injection with a mean change of 18.2 ± 32.57 pg/mL (95% CI -0.61 to 37.01, p = 0.04) and 15.46 ± 24.14 pg/mL (95% CI 1.53-29.40, p = 0.03), respectively. VEGF-A was significantly decreased with a mean change of -915.4 ± 831.72 pg/mL (95% CI -1395.62 to -435.18, p < 0.01). One patient was diagnosed with IOI, and the cytokine profile showed increased in aqueous pro-inflammatory cytokines (Exotaxin, G-CSF, IL-8, IL-10, IL-22, IL-10, MCP-1 and TNF- α) and decreased in VEGF-A level compared with baseline.

Our study demonstrated a significant increase in aqueous pro-inflammatory cytokines in eyes treated with intravitreal brolucizumab. Nearly all eyes studied showed no clinical signs of intraocular inflammation. The results suggested that type IV cell-mediated hypersensitivity could play a role in IOI following intravitreal brolucizumab injection.