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To determine whether CD163, a specific marker for M2 macrophages, is involved in the formation of preretinal fibrovascular membranes (FVMs) present in eyes with proliferative diabetic retinopathy (PDR).We measured the levels of soluble (s)CD163, periostin and vascular endothelial growth factor by sandwich ELISA in vitreous samples from 74 eyes of 62 patients with PDR, 20 eyes of 18 patients with proliferative vitreoretinopathy, and 56 eyes of 54 patients with non-diabetic ocular diseases (control group). Immunohistochemical analyses were performed to determine the expressions of CD68, CD163 and periostin in the surgically resected FVMs and idiopathic epiretinal membranes (ERMs).The concentrations of sCD163 and periostin in the vitreous were significantly higher in patients with PDR than in non-diabetic controls (p<0.0001). There was a strong correlation between the vitreous concentrations of sCD163 and periostin. The mean vitreous level of sCD163 was significantly higher in eyes with FVMs than in those without FVMs (epicentre only). The number and percentage of CD163+ macrophages were significantly higher in the FVMs than in the idiopathic ERMs. Immunohistochemical analysis showed co-localisation of CD163 and periostin in FVM cells.These findings indicate that the overexpression of CD163 by macrophages may be involved in the development of FVMs partly through periostin production.