Altered proportion of CCR2<sup>+</sup> and CX3CR1<sup>+</sup> circulating monocytes in neovascular age‐related macular degeneration and polypoidal choroidal vasculopathy

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Purpose: Ageing is the strongest predictor of neovascular age-related macular degeneration (AMD), where neuroinflammation is known to play a major role. Less is known about polypoidal choroidal vasculopathy (PCV), which is an important differential diagnosis to neovascular AMD. Here, we report plasma markers of inflammation with age (inflammaging) in patients with PCV, patients with neovascular AMD and a healthy age-matched control group. Methods: We isolated plasma from fresh venous blood obtained from participants (n = 90) with either PCV, neovascular AMD, or healthy maculae. Interleukin(IL)-1b, IL-6, IL-8, IL-10 and tumour necrosis factor receptor 2 (TNF-R2) were measured using U-PLEX Human Assays. Routine plasma Creactive protein (CRP) was measured using Dimension Vista 1500. Results: Patients with PCV had plasma levels of IL-1b, IL-6, IL-8, IL-10 and TNF-R2 similar to that in healthy controls. Patients with neovascular AMD had significantly higher plasma IL-1b, IL-6 and IL-10 than healthy controls, whereas no significant differences were observed for plasma IL-8 and TNF-R2. Differences between plasma IL-1b, IL-6 and IL-10 possessed a positive but weak ability in discriminating neovascular AMD from PCV. Both patients with PCV and patients with neovascular AMD had significantly higher levels of routine plasma CRP. Conclusion: Patients with PCV differ from patients with neovascular AMD in terms of plasma inflammaging profile. Apart from increased CRP, no signs of inflammaging were observed in patients with PCV. In patients with neovascular AMD, we find a specific angiogenesis-twisted inflammaging profile.

“…Although elements of altered immunology may be present in PCV (Subhi et al. , ), there is no strong evidence of an inflammaging‐related aetiology.…”

Section: Discussionmentioning

confidence: 99%

Plasma markers of chronic low‐grade inflammation in polypoidal choroidal vasculopathy and neovascular age‐related macular degeneration

Subhi

Nielsen

Molbech

et al. 2018

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“…; Subhi et al. ,b, ,b) which seem to play a complex intertwined role. Recent studies demonstrate that specific clinical features may be linked to specific immunological phenotypes in the systemic immunity (Singh et al.…”

Section: Introductionmentioning

confidence: 98%

“…Several studies have explored aetiological aspects of AMD and ageing (Subhi et al. , , ,b; Blasiak et al. ; Harris et al.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil‐to‐lymphocyte ratio in age‐related macular degeneration: a systematic review and meta‐analysis

Niazi

Nielsen

Sørensen

et al. 2019

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Age-related macular degeneration (AMD) is aetiologically linked to immunological ageing and dysfunction. One aspect of this is the altered neutrophil-tolymphocyte ratio (NLR), which in other domains have been associated with inflammation and angiogenesis, and therefore investigated in patients with AMD in several papers. In this systematic review and meta-analysis, we summarize findings in patients with AMD in relation to NLR, both qualitatively and quantitatively. We searched PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central and identified six studies from where we extracted data on 1178 individuals (777 patients with AMD and 401 healthy controls). Patients with AMD had a higher NLR (weighted mean difference: 0.37, CI 95% 0.08 to 0.66, p = 0.013) when compared to healthy controls. In subgroup analyses, we did not find a significant difference between patients with dry AMD and healthy controls (weighted mean difference: 0.34, CI 95% À0.03 to 0.69, p = 0.068), but did find a strong significant difference between patients with neovascular AMD and healthy controls (weighted mean difference: 0.54, CI 95% 0.23 to 0.86, p = 0.00068). Hence, we find that the association between AMD and elevated NLR may have stronger relevance to the neovascular subtype of AMD. However, the clinical value of measuring the NLR remains unclear.

“…In patients with PCV, monocytic CX3CR1 expression seem to correlate with the extent of BVN presence (Subhi et al. ), which suggests that CX3CR1 plays a role in vessel formation. Looking more specifically at the role of CX3CR1 on monocytes, Landsman et al.…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence to suggest that the MCP‐1 receptor CCR2 expressed on circulating monocytes may play a role in PCV (Subhi et al. , 2019a), whereas the role of the IP‐10 receptor CXCR3 is more unclear and so far only reported in relation to T‐helper cells (Subhi et al. 2019b).…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of inflammatory chemokines in patients with polypoidal choroidal vasculopathy

Sørensen

Subhi

Molbech

et al. 2019

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Purpose: Chemokines are a group of cytokines that guide immune cell migration. We studied plasma levels of inflammatory chemokines in patients with polypoidal choroidal vasculopathy (PCV) and compared with healthy agematched control individuals. Methods: This was a clinic-based prospective case-control study of participants (n = 60) with either PCV (n = 26) or age-matched healthy controls (n = 34). We sampled fresh venous blood and isolated plasma for analysis. We used U-PLEX Human Assays to quantify concentrations of the inflammatory chemokines MCP-1/CCL2, RANTES/CCL5, eotaxin/CCL11, IP-10/CXCL10 and fractalkine/CX3CL1. Results: Plasma levels of fractalkine was significantly higher in patients with PCV when compared to healthy controls (mean AE SD: 7291 AE 2461 pg/ml versus 5879 AE 2001 pg/ml; p = 0.021). Plasma levels of MCP-1 (p = 0.846), RANTES (p = 0.288), eotaxin (p = 0.496) and IP-10 (p = 0.352) did not differ significantly between the groups. To evaluate possible biomarker quality of fractalkine, we used a ROC analysis and found a positive but weak discriminatory ability (AUC = 0.68). Conclusion: Patients with PCV have a higher plasma level of fractalkine. Although the differences do not possess strong biomarker qualities, they inform on disease processes of a poorly understood disease and suggest that the fractalkine-CX3CR1 axis may be involved. As this study did not investigate local chemokine concentrations, we are unable to confirm or disprove any local chorioretinal interaction, and our findings should be interpreted with such caution.