Purpose: 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.
Design: Experimental pilot study.
Participants: Patients with neovascular AMD seen at Washington University School of Medicine in St. Louis and BJC Health System.
Methods: 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).
Main outcome measures: Identification of immune cells associated with high treatment burden.
Results: Gene expression signature of CD16+ monocytes may be associated with high treatment burden.
Conclusions: 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.
Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Keywords: AMD; CNV; Macrophage; Monocyte; VEGF.
© 2023 by the American Academy of Ophthalmology.