Association of CD11b+ Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.


Journal

JAMA ophthalmology
ISSN: 2168-6173
Titre abrégé: JAMA Ophthalmol
Pays: United States
ID NLM: 101589539

Informations de publication

Date de publication:
01 05 2019
Historique:
pmc-release: 07 03 2020
pubmed: 8 3 2019
medline: 19 2 2020
entrez: 8 3 2019
Statut: ppublish

Résumé

CD11b+ immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. To investigate whether the proportion of CD11b+ circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). These observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark. Proportion of CD11b+ circulating monocytes. The estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b+ circulating monocytes and the correlation between these values. The angiogenic role of CD11b+ circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2. Eighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b+ monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P = .004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P = .002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P = .005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P = .004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P = .002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P < .001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P = .30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P = .02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P = .005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b+ monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity. Results of this study demonstrated that the proportion of circulating CD11b+ monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy.

Identifiants

pubmed: 30844038
pii: 2726702
doi: 10.1001/jamaophthalmol.2019.0010
pmc: PMC6512268
doi:

Substances chimiques

Angiogenesis Inhibitors 0
CD11b Antigen 0
Vascular Endothelial Growth Factor A 0

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

515-522

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Auteurs

Yousif Subhi (Y)

Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark.
Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

Marie Krogh Nielsen (M)

Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark.
Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

Christopher Rue Molbech (CR)

Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark.
Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

Mads Krüger Falk (M)

Department of Ophthalmology, Zealand University Hospital Næstved, Næstved, Denmark.

Amardeep Singh (A)

Department of Clinical Sciences Lund, Division of Ophthalmology, Skane University Hospital, Lund University, Lund, Sweden.

Thomas Vauvert Faurschou Hviid (TVF)

Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital, Roskilde, Denmark.

Mogens Holst Nissen (MH)

Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
Eye Research Unit, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Torben Lykke Sørensen (TL)

Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark.
Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

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Classifications MeSH