Association of Upregulated Angiogenic Cytokines With Choroidal Abnormalities in Chronic Central Serous Chorioretinopathy

Abstract

PURPOSE. To clarify the distinct molecular pathogenesis of central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV). METHODS. Aqueous humor (AH) was collected from 18 acute CSC, 20 chronic CSC, and 20 PNV patients. Concentrations of 30 cytokines in the AH were analyzed using a multiplex bead immunoassay, and the cytokine profiles were compared among these three groups of patients. The areas of choroidal vascular hyperpermeability (CVH) and choroidal thickness (CT), including measurement of the vascular layers, were investigated to analyze the features of choroidal abnormality in acute CSC, chronic CSC, and PNV. Additionally, associations between cytokine profiles and choroidal abnormalities were analyzed. RESULTS. Proinflammatory cytokines, IL-6 and IL-8 were significantly upregulated in the chronic CSC group compared with the acute CSC or PNV groups. Angiogenic cytokines and VEGF-A were upregulated at levels that almost reached significance along with disease progression from acute to chronic CSC, whereas the upregulation was not significant from chronic CSC to PNV. In the chronic CSC group, strong positive correlations were confirmed between VEGF-A and placental growth factor (PlGF) (r ¼ 0.75, P < 0.001) and IL-6 and VEGF-A (r ¼ 0.74, P < 0.001), and angiogenesis-related cytokines were positively correlated with the typical choroidal abnormalities, areas of CVH, mean CT, and mean large choroidal vessel layer thickness. However, there was no association between these choroidal abnormality parameters and AH cytokines in the PNV group. CONCLUSIONS. The results suggest that choroidal abnormalities in chronic CSC may be associated with upregulated angiogenesis.

The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis

“…Intraocular concentrations of IL-6 and IL-8 have been reported to be closely associated with the volume of MO and size of active CNV 175 , 182 . Moreover, IL-6 and IL-8 are significantly upregulated in the chronic CSC group compared with the acute CSC or PNV groups 272 . Therefore, further studies are needed to elucidate the role of IL-6 in the aetiology of AMD, CNV and pachychoroid spectrum diseases.…”

Complement Activation Products and Cytokines in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration

“…22,31 Also, elevation of complement activation products (complement factors Ba, H, I, C3a, 25,26 adhesion molecule-1, IL-6, IL-8, IP-10, C-reactive protein, angiopoietin-2, human growth factor, tissue inhibitor of metalloproteinases 1, C-X-C motif chemokines 12 and 13, tumor necrosis factor-α, IL-31, leukemia inhibitory factor, and stromal cell-derived factor-1-α. [7][8][9][10][11][12][13][14][15][16][32][33][34][35][36] A recent study that summarized these cytokine networks using cluster analysis suggested that VEGF and MCP-1 were key factors in the development of nAMD. 15 Although complement factors and angiogenic cytokines were associated with nAMD development, their relationships in the aqueous humor have not been fully determined.…”

Long-term treatment response after intravitreal bevacizumab injections for patients with central serous chorioretinopathy

“…The long-term treatment results of this study suggest that IVBIs can remain as a treatment option for patients with CSC. Previously, some studies have investigated the cytokines in the aqueous humor of patients with CSC, resulting in inconsistent results [40][41][42][43]. Some studies suggest that aqueous VEGF level was not significantly elevated in the patients with CSC, supporting ineffectiveness of anti-VEGF therapy in these patients [40,41].…”

“…One study demonstrated that the VEGF-A level is significantly higher in bevacizumab responders than in non-responders, suggesting that VEGF may contribute to the pathogenesis of CSC [42]. Another study found that proinflammatory cytokines, such as interleukin (IL)-6 and IL-8, are significantly upregulated in patients with chronic CSC compared to those with acute CSC [43]. Angiogenic cytokines and VEGF-A are also upregulated more in patients with CSC than in those with acute CSC [43].…”

“…Another study found that proinflammatory cytokines, such as interleukin (IL)-6 and IL-8, are significantly upregulated in patients with chronic CSC compared to those with acute CSC [43]. Angiogenic cytokines and VEGF-A are also upregulated more in patients with CSC than in those with acute CSC [43]. IVBIs significantly reduce choriocapillaris endothelial cell fenestrations [44,45].…”