Vitreous Fibronectin and Fibrinogen Expression Increased in Eyes With Proliferative Diabetic Retinopathy After Intravitreal Anti-VEGF Therapy

Abstract

PURPOSE. To evaluate vitreous humor (VH) protein expression profiles in patients with proliferative diabetic retinopathy (PDR), with and without intravitreal injection (IVI) of antivascular endothelial growth factor (anti-VEGF) before vitrectomy. METHODS.We enrolled consecutive PDR patients who needed pars plana vitrectomy (PPV) with or without IVI or pan-retinal photocoagulation (PRP). Visual acuity, duration, and treatment of diabetes mellitus, ocular treatment history, and fundus examinations were recorded. VH samples were collected without artificial humor infusion. Label-free quantitative proteomics analysis was performed to determine the protein expression profiles of VH samples. Enzymelinked immunosorbent assays were performed to validate the proteomics results.RESULTS. PDR patients who underwent IVI at a mean of 5.8 days (range, 3-8 days) before PPV (IVI group, n ¼ 12) were younger than PDR patients with a history of PRP (PRP group, n ¼ 29) and untreated PDR patients (control group, n ¼ 21). The duration of diabetes mellitus was similar in the three groups. Label-free quantitative proteomics analysis showed that the signal intensities for fibronectin, fibrinogen a chain, fibrinogen b chain, fibrinogen c chain, VEGF receptor 1 (VEGFR1), and VEGFR2 were significantly greater in the IVI group than in the other two groups. Enzyme-linked immunosorbent assays validated the results for fibronectin and fibrinogens, but found no significant differences in VEGF or VEGFR2 concentrations. VEGFR1 expression was significantly greater in the IVI and PRP groups than in the control group.CONCLUSIONS. VH fibronectin and fibrinogen concentrations were highest in the IVI patients, which may promote fibrin-fibronectin complexation and fibrosis in eyes with PDR.

Prognostic factors of revitrectomy for complications in eyes with proliferative diabetic retinopathy: a retrospective multicentre study

“…; Wei et al. ). Randomized control trials for the timing of preoperative anti‐VEGF injection in vitrectomy for eyes with PDR should be needed.…”

Angiopoietin-1 Promotes the Integrity of Neovascularization in the Subcutaneous Matrigel of Type 1 Diabetic Rats

“…Studies have found that anti-VEGF therapy could improve diabetic nephropathy and retinopathy [6, 7]. However, in recent years, more and more basic and clinical studies have found that anti-VEGF might lead to proteinuria [8], deterioration of renal disease, and renal thrombotic microvascular disease [9], and there was no clinical improvement in most patients with retinopathy [10]. This indicates that a certain amount of VEGF is required to maintain organ function in physiological state.…”

Anti-Vascular Endothelial Growth Factor Therapy as an Alternative or Adjunct to Pan-Retinal Photocoagulation in Treating Proliferative Diabetic Retinopathy: Meta-Analysis of Randomized Trials

“…Obeid et al, 2019(Obeid et al, 2019 further investigated 59 PDR patients who were LTFU for over 6 months, in which anti-VEGF monotherapy manifested worse anatomic and functional outcomes. Wei et al (2017) also reported that fibronectin and fibrinogen concentrations in vitreous humor of intravitreal anti-VEGF injection group, which might promote fibrosis in eyes with PDR. Thus, many problems of anti-VEGF therapy remain to be solved.…”