Differential association of elevated inflammatory cytokines with postoperative fibrous proliferation and neovascularization after unsuccessful vitrectomy in eyes with proliferative diabetic retinopathy

Abstract

Background: Pars plana vitrectomy is the only treatment for advanced proliferative diabetic retinopathy (PDR). However, vitrectomy is not always successful despite current progress in vitreoretinal surgical techniques. The aim of our study was to investigate whether the vitreal concentrations of MCP-1, IL-6, IL-8, and VEGF are elevated after unsuccessful vitrectomy in patients with PDR and to investigate whether the altered levels of these cytokines are associated with the cause for the reoperation.

Patients and methods: Vitreous samples were collected from 263 eyes of 233 patients: PDR (n=129 eyes), proliferative vitreoretinopathy (PVR; n=24 eyes) and nondiabetic controls (n=110 eyes) prior to vitrectomy. Vitreous samples were also collected from 14 eyes of 14 patients with PDR before vitrectomy and from the same 14 eyes before a second vitrectomy for reoperation. The levels of MCP-1, IL-6, IL-8, and VEGF were measured by flow cytometry using a cytometric bead array (CBA) assay.

Results: The mean concentrations of vitreal MCP-1, IL-6, IL-8, and VEGF were significantly higher in patients with PDR and PVR (P<0.01). There were significantly high correlations among the concentrations of MCP-1, IL-6, and IL-8, whereas the correlation of VEGF with the other 3 cytokines was lower. Among the 14 patients who required reoperation, the mean vitreal concentrations of MCP-1, IL-6, and IL-8 were higher than that at the time of the initial vitrectomy (P<0.01). At the time of the reoperation vitrectomy, the mean vitreous level of MCP-1, IL-6, and IL-8 in eyes with fibrous proliferation was higher than in those without fibrous proliferation (P<0.05). In contrast, VEGF in eyes with neovascular glaucoma (NVG) or anterior hyaloidal fibrovascular proliferation (AHFVP) was higher than in the eyes without NVG and AHFVP (P<0.05).

Conclusion: The elevated levels of MCP-1, IL-6, and IL-8 may be the cause of the postoperative fibrous proliferation. In contrast, VEGF may be the cause of the neovascularization after unsuccessful vitrectomy in the eyes of PDR patients.

Keywords: cytokines; fibrous proliferation; neovascularization; proliferative diabetic retinopathy; reoperation; vitrectomy.

Figure 1

Vitreous concentrations of MCP-1 (A), IL-6 (B), IL-8 (C), and VEGF (D) in the vitreous samples at the first vitrectomy in PDR patients, and the same vitrectomized PDR patients at the time of the reoperation. Note: *P<0.001 (Wilcoxon matched-pairs signed-rank tests). Abbreviations: PDR, proliferative diabetic retinopathy; NS, not significant.

Figure 2

Intravitreous levels of MCP-1, IL-6, IL-8, and VEGF at the time of reoperation vitrectomy and their correlations with the presence or absence of tractional retinal detachment (TRD) due to fibrous proliferation. Notes: The correlation was determined by the Spearman coefficient of correlation. (A) Intravitreous level of MCP-1 in eyes with and without fibrous proliferation (*P<0.01). (B) Intravitreous level of IL-6 in eyes with and without fibrous proliferation (**P<0.05). (C) Intravitreous level of IL-8 in the presence or absence of fibrous proliferation (**P<0.05). (D) Intravitreous level of VEGF in the presence or absence of fibrous proliferation. Abbreviation: NS, not significant.

Figure 3

Intravitreous levels of MCP-1, IL-6, IL-8, and VEGF at the time of reoperation vitrectomy and their correlations with the presence or absence of neovascular glaucoma (NVG) and/or anterior hyaloidal fibrovascular proliferation (AHFVP). Notes: The correlation was determined by the Spearman coefficient of correlation. (A) Intravitreous level of MCP-1 in eyes with and without NVG and/or AHFVP. (B) Intravitreous level of IL-6 in eyes with and without NVG and/or AHFVP. (C) Intravitreous level of IL-8 according to the presence or absence of NVG and/or AHFVP. (D) Intravitreous level of VEGF according to the presence or absence of NVG and/or AHFVP (*P<0.05). Abbreviation: NS, not significant.

Figure 4

Vitreous concentrations of MCP-1 (A), IL-6 (B), IL-8 (C), and VEGF (D) in patients with an idiopathic epiretinal membrane or a macular hole (nondiabetic controls; n=110), and also eyes with proliferative diabetic retinopathy (PDR; n=129), and proliferative vitreoretinopathy (PVR; n=24). Notes: The horizontal lines are the mean values. *P<0.01, **P<0.001 (Mann–Whitney U test).