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Updated: Jun 29, 2025
Author Spotlight: Overcoming Anti-VEGF Resistance Through Advanced Vascular Morphology Assessment in Choroidal Neovascularization
Published on: August 11, 2023
Cell-specific Systemic Immune Signatures Associated with Treatment Burden in Neovascular Age-related Macular
Joseph B Lin1,2, Andrea Santeford1, Darksha Usmani1
1John F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri.
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.
