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

Niazi, Siar; Nielsen, Marie Krogh; Sørensen, Torben Lykke; Subhi, Yousif

doi:10.1111/aos.14072

Cited by 40 publications

(33 citation statements)

References 49 publications

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“…LCN2 is known to be produced predominately by neutrophils in the immune system (27). Previously, we and others have shown that nAMD patients had a higher percentage of circulating neutrophils compared to healthy controls (18,19,25,41). In this study, we observed a positive correlation between plasma levels of LCN2 and circulating neutrophils in nAMD patients but not in healthy controls ( Figure 2C-D).…”

Section: Discussionsupporting

confidence: 65%

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

Chen

Yang

Lechner

et al. 2020

Preprint

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Background: Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results: One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r=0.29, P=0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r=0.34, p=0.0007) but not in healthy controls (r=0.057, p=0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. Conclusions: Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.

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Section: Discussionsupporting

confidence: 65%

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

Chen

Yang

Lechner

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…LCN2 is known to be produced predominately by neutrophils in the immune system [27]. Previously, we and others have shown that nAMD patients had a higher percentage of circulating neutrophils compared to healthy controls [18,19,25,37]. In this study, we observed a positive correlation between plasma levels of LCN2 and circulating neutrophils in nAMD patients but not in healthy controls (Figure 2A-B).…”

Section: Discussionsupporting

confidence: 64%

Plasma levels of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

Chen

Yang

Lechner

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Previously, we and others have reported high populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results: One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r=0.29, P=0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r=0.34, p=0.0007) but not in healthy controls (r=0.057, p=0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. Conclusions: Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.

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“…It can also stimulate T cell activation by expressing MHC class II [118]. A stronger correlation has been shown between nAMD and neutrophil-to-lymphocyte ratio (NLR) elevation compared with healthy controls [119], and NLR is related to disease severity as well as CNV and lesion size [120,121]. Neutrophils are associated with retinal angiogenesis in laser-induced CNV.…”

Section: Neutrophilsmentioning

confidence: 99%

The Role of Inflammation in Age-Related Macular Degeneration

Tan¹,

Zou²,

Yoshida³

et al. 2020

Int. J. Biol. Sci.

121

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Age-related macular degeneration (AMD) is a blinding eye disease which incidence gradually increases with age. Inflammation participates in AMD pathogenesis, including choroidal neovascularization and geographic atrophy. It is also a kind of self-protective regulation from injury for the eyes. In this review, we described inflammation in AMD pathogenesis, summarized the roles played by inflammation-related cytokines, including pro-inflammatory and anti-inflammatory cytokines, as well as leukocytes (macrophages, dendritic cells, neutrophils, T lymphocytes and B lymphocytes) in the innate or adaptive immunity in AMD. Possible clinical applications such as potential diagnostic biomarkers and anti-inflammatory therapies were also discussed. This review overviews the inflammation as a target of novel effective therapies in treating AMD.

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

Cited by 40 publications

References 49 publications

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

Plasma levels of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

The Role of Inflammation in Age-Related Macular Degeneration

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