Chemokine System Changes Drive Age-Related Macular Degeneration and Influence Treatment Outcomes

PURPOSE: The chemokine system is associated with age-related macular degeneration (AMD), shown in previous studies. In this study, we investigate these chemokines and chemokine receptors and their association with treatment response in neovascular AMD (nAMD), and association to intermediate AMD (iAMD).

METHODS: In this prospective cohort study, patients with nAMD, iAMD, and healthy controls were included. The initial and 1-year treatment response was evaluated in patients with nAMD. Plasma chemokine concentrations of CCL2, CCL3, CCL4, CCL20, CXCL8, and CXCL10 were measured with immunoassays. Chemokine receptor expression levels of CCR1, CCR2, CCR5, CCR6, CXCR2, CXCR3, and CX3CR1 on circulating T cells and monocytes were measured with flow cytometry. Correlation network analyses were performed of the chemokine system. Genotyping for CFH and ARMS2 risk polymorphisms was performed in patients with nAMD.

RESULTS: Patients with nAMD with poor initial treatment response had significantly lower proportions of CD4+CXCR3+, CCR5+ classical monocytes, and CCR2+ non-classical monocytes compared with good initial responders (all P < 0.05). Patients with nAMD with poor 1-year treatment response had significantly lower CD4+CXCR3+ and CCR2+ non-classical monocytes compared to good 1-year responders (both P < 0.05). Correlation networks revealed a more complex regulation in partial and poor initial treatment responders. Multiple chemokines and chemokine receptors significantly correlated with the risk genotypes of CFH and ARMS2.

CONCLUSIONS: Patients with nAMD with poor treatment response had dysregulation of the chemokine system. The chemokine system might be a potential target of novel treatment in nAMD. Further studies are needed to clarify the chemokine system's role in nAMD treatment response.