Aqueous Humor Mediator and Cytokine Aberrations in Diabetic Retinopathy and Diabetic Macular Edema: A Systematic Review and Meta-Analysis

Table 1

The characteristics of included studies about DR and control groups.

First author (year)	Country	Study design	DR definition	Measurements	DR			Non-DR			Cytokines
					Age (years)	M/F	Total	Age (years)	M/F	Total
Shinoda (1999)	Japan	Case-control	ETDRS	ELISA	33-82	N.A	43	34-86	N.A	47	HGF and VEGF
Endo (2001)	Japan	Case-control	ETDRS	ELISA		N.A	36		N.A	102	VEGF and CML
Cheung (2012)	Singapore	Case-control	Dilated fundoscopic examination	Magnetic color bead-based multiplex assay		18/9	27		19/25	44	IL-1Ra, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-17, G-CSF, GMCSF, IFN-γ, MCP-1 (CCL2), MIP-1β (CCL4), IL-8 (CXCL8), MIG (CXCL9), IP-10 (CXCL10), TNF-α, IFN-α, and VEGF
Gverović (2012)	Croatia	Case-control	ETDRS	ELISA	61-83	10/13	23	61-89	10/26	36	IL-12
Dong (2013)	China	Case-control	ETDRS	Multiplex bead immunoassay	N/A	N.A	N/A		57/45	102	VEGF, IL-1β, IL-6, IL-8, MCP-1, IP-10, IL-10, and IL-12
Fulgêncio Cunha (2013)	Brazil	Case-control	N/A	ELISA	N/A	N.A	15	N.A	N.A	30	VEGF and IL-6
Kocabora (2015)	Turkey	Case-control	ETDRS	ELISA		10/12	22		22/23	45	TNF-α and CRP
Vujosevic (2016)	Italy	Case-control	N/A	RayBiotech technology		6/5	11		9/15	24	GM-CSF, IFN, IL, IP-10, MCP, M-CSF, MIP, RANTES, sTNF-R, and TNF
Chen (2017)	China	Case-control	DRDSS	Multiplex bead immunoassay		54/47	101		54/47	101	IL-1RA, IL-1β, IL-1α, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-9, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, TNF-α, TNFβ/LTA, IFN-γ, and IFN-α
Wu (2017)	China	Case-control	Indirect ophthalmoscopy	Becton Dickinson CBA software	66-67	13/16	29	69.3	8/24	32	IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-γ, TNF, and VEGF
Khuu (2017)	Canada	Case-control	ETDRS	Luminex xMAP suspension array		N.A	15		N.A	17	FGF-1 & FGF-2, ANG-2, IL-8, leptin, stromal-derived factor-1, EGF, TGF-b1 and TGF-b2, G-CSF, PDGFs, VEGF, and ET-1
Houssen (2017)	Egypt	Case-control	FFA	ELISA		N.A	40		N.A	40	IL-27

N.A: not applicable; ETDRS: Early Treatment Diabetic Retinopathy Study; DRDSS: International Clinical Diabetic Retinopathy Disease Severity Scale; ELISA: enzyme-linked immunosorbent assay; HGF: human growth factor; VEGF: vascular endothelial growth factor; IL: interleukin; MCP: monocyte chemotactic protein; CML: carboxymethyl-lysine; G-CSF: granulocyte colony-stimulating factor; GMCSF: granulocyte macrophage colony-stimulating factor; IFN: interferon; MIP: macrophage inflammatory protein; MIG: monokine induced by IFN-γ; IP: interferon gamma-induced protein; M-CSF: macrophage colony-stimulating factor; RANTES: regulated and normal T cell expressed and secreted; sTNF-R: soluble tumor necrosis factor receptor; FGF: fibroblast growth factor; ANG: angiopoietins; TGF: transforming growth factor; EGF: epidermal growth factor; PDGF: platelet-derived growth factor; ET: erythropoietin, endothelin; M/F: male/female.