TY - JOUR
T1 - Association of CD11b+ Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy
AU - Subhi, Yousif
AU - Krogh Nielsen, Marie
AU - Molbech, Christopher Rue
AU - Falk, Mads Krüger
AU - Singh, Amardeep
AU - Hviid, Thomas Vauvert F.
AU - Nissen, Mogens Holst
AU - Sørensen, Torben Lykke
PY - 2019/5
Y1 - 2019/5
N2 - Importance: 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. Objective: 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). Design, Setting, and Participants: 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. Exposures: Proportion of CD11b+ circulating monocytes. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.
AB - Importance: 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. Objective: 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). Design, Setting, and Participants: 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. Exposures: Proportion of CD11b+ circulating monocytes. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.
U2 - 10.1001/jamaophthalmol.2019.0010
DO - 10.1001/jamaophthalmol.2019.0010
M3 - Journal article
C2 - 30844038
SN - 2168-6165
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
ER -