Circulating monocytes differentiates neovascular age-related macular degeneration from polypoidal choroidal vasculopathy

Session Details

Session Title: Free Paper Session 4: AMD II

Session Date/Time: Thursday 07/09/2017 | 11:00-12:30

Paper Time: 11:24

Venue: Room 111

First Author: : Y.Subhi DENMARK

Co Author(s): :    M. Nielsen   C. Molbech   A. Singh   M. Nissen   T. Sorensen                 

Abstract Details

Purpose:

We previously investigated the blood of patients with neovascular AMD (nAMD) and found increased percentages of monocytes that were positive of CD11b (facilitates adhesion and migration) and CD200 (regulates retinal microglia). The CD11b expression may be a consequence of VEGF-mediated monocyte chemotaxis and activation, whereas CD200 expression suggest microglial involvement and neurodegeneration in nAMD. In this study, we investigated differences and similarities in the blood of patients with nAMD and polypoidal choroidal vasculopathy (PCV). Despite distinct retinal manifestation, it is still debated whether they represent different disease entities or different clinical manifestation of the same disease.

Setting:

Prospective case-control study of patients with nAMD, patients with PCV, and healthy age-matched control individuals.

Methods:

All participants were subjected to a structured interview, detailed retinal imaging (fundus autofluorescence imaging, digital colour fundoscopy, and spectral-domain optical coherence tomography), and fluorescein and indocyanine green angiography were performed in patients suspected of retinal disease. Participants with active immune disease or cancer were not included due to their existing immune dysfunction. Fresh venous blood was obtained and stained using monoclonal antibodies targeted CD11b and CD200. Flow cytometric analyses were made within 4 hours of blood sampling. Based on power calculations, we recruited ≥26 participants in each group during the study period from February 2015 to February 2017. Patients were recruited from our outpatient retinal program. Healthy age-matched controls were recruited among healthy relatives of the participants. This was an intentional strategy to better match the control group in terms of lifestyles and exposures. Data extraction was made in March 2017 in a blinded-fashion by two investigators. Our outcome measures were the percentages of monocytes that were CD11b+, CD200+, and CD11b+CD200+.

Results:

Patients with nAMD (n=35) had a higher percentage of CD11b+ (median %: 95), CD200+ (median %: 17), and CD11b+CD200+ (median %: 18) monocytes compared with patients with PCV (n=27) (P=0.004, P=0.024, P=0.035; respectively for CD11b+, CD200+, and CD11b+CD200+; Mann-Whitney U-test) and healthy age-matched controls (n=28) (P<0.001, P=0.036, P=0.048; respectively for CD11b+, CD200+, and CD11b+CD200+; Mann-Whitney U-test). Patients with PCV had a higher percentage of CD11b+ (median %: 93) compared with healthy age-matched controls (median %: 90) (P=0.027; Mann-Whitney U-test), but percentages of CD200+ (median % in PCV: 13; median % in control: 14; P=0.686; Mann-Whitney U-test) and CD11b+CD200+ (median % in PCV: 13; median % in control: 15; P=0.649; Mann-Whitney U-test) monocytes were similar.

Conclusions:

Systemic contribution of microglia regulation through circulating monocytes play a role in nAMD, but not PCV. Increased expression of CD11b reflect that VEGF-mediated activation of monocytes may be present in both nAMD and PCV, but that monocytes may play a bigger role in nAMD. Taken together, we find that nAMD and PCV not only differs in terms of retinal manifestation, but also in their systemic activation of immune cells.

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