Expression of aqueous cytokines and their correlation with retinal morphological biomarkers in nAMD patients

Neovascular age-related macular degeneration (nAMD) is characterized by pathological neovascularization in the macula, leading to irreversible central vision loss. This study aimed to evaluate cytokine profiles in the aqueous humor of nAMD patients and explore correlation between specific cytokines, clinical characteristics, and retinal morphological features.

Our protocol was registered on Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2500106190 and approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (ID: 20231375). A total of 94 patients with nAMD and 34 cataract patients as the control group were enrolled. Aqueous humor samples were collected before anti-VEGF treatment or cataract surgery, and analyzed using cytometric bead array (CBA) for cytokines (MCP-1, ICAM-1, VCAM-1, CA-1, β-FGF, PPK/PK, and VEGF). Retinal structural biomarkers were assessed using optical coherence tomography (OCT), with statistical analysis performed to evaluate correlations between cytokine levels and retinal morphology.

Compared to cataract patients, nAMD patients exhibited elevated levels of CA-1, PPK/PK, ICAM-1, VCAM-1, and MCP-1 (P < 0.05). Baseline best-corrected visual acuity (BCVA) was reduced in nAMD patients with intraretinal fluid (IRF) or pigmentation compared to those without (P < 0.05). Visit BCVA also deteriorated in patients with fibrosis (P < 0.05). Additionally, central foveal thickness (CTR) was significantly thinner in patients with PED or SRF (P < 0.05). Visit BCVA demonstrated positive correlations with baseline BCVA (r = 0.689, P < 0.001). In contrast, the presence of fibrosis and elevated MCP-1 concentration was associated with a poorer visual outcome. In correlation analysis, β-FGF exhibited a negative correlation with CA-1, PPK, ICAM-1. VCAM-1 and MCP-1.

In this cross-sectional study, the presence of IRF was significantly associated with reduced BCVA in nAMD patients. Baseline BCVA emerged as a critical predictor of visual prognosis in nAMD. Notably, retinal fibrosis development and elevated MCP-1 level linked to worse clinical outcomes, underscoring their potential as therapeutic targets. While recent anti-VEGF injections decreased VEGF levels in aqueous humor of nAMD patients, the impact of these agents on other cytokines remain unclear, suggesting a need for adjunct therapies to address multifaceted pathogenic pathways.