Cell-specific Systemic Immune Signatures Associated with Treatment Burden in Neovascular Age-related Macular Degeneration

Abstract

Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined. The purpose of this study was to identify transcriptional signatures of circulating immune cells that are associated with high anti-VEGF treatment burden. Experimental pilot study. Patients with neovascular AMD seen at Washington University School of Medicine in St. Louis and BJC Health System. We profiled by single cell RNA sequencing the peripheral blood mononuclear cells of 27 treatment-experienced patients with wet AMD. We stratified this cohort into 2 groups with low and high treatment burden (≤5 or ≥ 6 injections in the past 12 months, respectively). Identification of immune cells associated with high treatment burden. Gene expression signature of CD16+ monocytes may be associated with high treatment burden. These studies delineate potential signatures of circulating immune cells that may be associated with high treatment burden in neovascular AMD, potentially informing the development of diagnostic predictors of anti-VEGF response and new precision medicine-based approaches to complement anti-VEGF therapies. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.