Changes in Aqueous Humor Cytokine Profile Following Intravitreal Brolucizumab Injection.

Purpose: 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.

Patients and methods: 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.

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.

Conclusion: 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.