Abstract
Purpose :
We aimed to quantitatively summarize data on inflammatory cytokines associated with RVO.
Methods :
A systematic review of peer-reviewed English-language articles from PubMed, Ovid MEDLINE, Ovid MEDLINE Epub (ahead of print) and EMBASE Classic plus EMBASE was performed. Data on aqueous and vitreous cytokine concentrations were extracted by two independent investigators. Data was pooled using a random-effects model with the Comprehensive Meta-analysis software. Effect sizes were generated as standardized mean differences (SMD) of cytokine concentrations between patients with RVO and healthy controls.
Results :
Among the 3996 eyes in 97 studies, concentrations of IL-4 (SMD=0.52, 95% confidence interval (CI)=0.15 to 0.88, p=0.006), IL-6 (SMD=0.76, 95% CI=0.40 to 1.11, p<0.0001), IL-8 (SMD=1.03, 95% CI=0.77 to 1.29, p<0.00001), IL-10 (SMD=0.69, 95% CI=0.43 to 0.95, p<0.00001), IL-15 (SMD=0.55, 95% CI=0.22 to 0.88, p=0.001), ANGPT (SMD=1.99, 95% CI=1.06 to 2.92, p<0.0001), IFN-γ (SMD=0.69, 95% CI=0.25 to 1.13, p=0.002), MCP-1 (SMD=1.21, 95% CI=0.82 to 1.59, p<0.00001), PDGF-AA (SMD=0.68, 95% CI=0.25 to 1.10, p=0.002), and VEGF (SMD=1.17, 95% CI=0.91 to 1.43, p=0.001) were significantly higher in patients with RVO when compared to healthy controls. No differences or failed sensitivity analyses were found between patients with RVO and healthy controls for the concentrations of IL-1α (SMD=0.53, 95% CI=0.11 to 0.94, p=0.01), IL-1β (SMD=0.76, 95% CI=-0.10 to 1.63, p=0.08), IL-2 (SMD=0.55, 95% CI=0.14 to 0.96, p=0.009), IL-12 (SMD=0.61, 95% CI=0.09 to 1.12, p=0.02), IL-13 (SMD=0.39, 95% CI=-0.20 to 0.97, p=0.20), b-FGF (SMD=0.64, 95% CI=-0.44 to 1.73, p 0.25), PEDF (SMD=0.36, 95% CI=-1.64 to 2.36, p= 0.73), TGF-β (SMD=2.22, 95% CI=0.42 to 4.03, p=0.02), and TNF-α (SMD=-0.14, 95% CI=-0.80 to 0.52, p=0.67) cytokines. Too little data made the comparison impossible for CXCL9, CXCL12, EGF, eotaxin, FGF-6, G-CSF, GM-CSF, ICAM-1, IGFBP, IL-5, IL-7, IL-9, IL-17, IL-18, IL-23, MIP-1, MMP, PDGF-BB, PGF, RANTES, SAA, sICAM-1, sVEGFR, TIMP-4, or TSG-14.
Conclusions :
Our meta-analysis demonstrated higher aqueous and vitreous concentrations of IL-4, IL-6, IL-8, IL-10, IL-15, ANGPT, IFN-γ, MCP-1, PDGF-AA, and VEGF in patients with RVO, strengthening the clinical evidence that RVO is accompanied by an inflammatory response and that cytokines in addition to VEGF have the potential to be useful biomarkers and therapeutic targets in RVO.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.