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

Autor: Joseph B. Lin, BS, Andrea Santeford, MS, Darksha Usmani, MS, Aaditya V. Shah, MD, Philip A. Ruzycki, PhD, Rajendra S. Apte, MD, PhD
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Ophthalmology Science, Vol 4, Iss 2, Pp 100410- (2024)
Druh dokumentu: article
ISSN: 2666-9145
DOI: 10.1016/j.xops.2023.100410
Popis: 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 Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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