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Comparison of before versus after intravitreal bevacizumab injection, growth factor levels and fibrotic markers in vitreous samples from patients with proliferative diabetic retinopathy

  • Retinal Disorders
  • Published:
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Abstract

Purpose

In diabetic retinopathy patients, intravitreal bevacizumab (IVB) injections are widely used to facilitate dissection of retinal fibrovascular membranes during surgery, reduce the rate of perioperative hemorrhage, and prevent recurrent neovascularization. Previous studies have shown that IVB may worsen fibrosis and thereby impair vision. The aim of this study was to determine which markers are associated with fibrosis.

Methods

Twenty-three patients with proliferative diabetic retinopathy (PDR) underwent pars plana vitrectomy (PPV) with IVB pretreatment for intraocular hemorrhage (IOH) and/or tractional retinal detachment (TRD). Vitreous samples were obtained at the time of IVB injection and again at the beginning of PPV, about a week later. Using Western blot analysis, the concentrations of vascular endothelial growth factor (VEGF), placental growth factor (PIGF), insulin like growth factor-1 (IGF-1), angiogenin-1 (Ang-1), and vascular endothelial cadherin (VE-cadherin) were measured in vitreous samples.

Results

After treatment with IVB, VEGF, PIGF, and VE-cadherin concentrations in the vitreous significantly decreased (p < 0.001, p < 0.001, and p = 0.001, respectively), whereas the concentrations of IGF-1 increased (p = 0.001). There were no significant changes in Ang-1 concentrations in the vitreous after IVB injection (p = 0.732). There were no statistically significant differences in VEGF-A, PIGF, VE-cadherin, IGF, and Ang-1 levels before and after IVB injection when the IOH and TRD groups underwent subgroup analysis (p = 0.696, p = 0.516, p = 0.498, p = 0.188, and p = 0.243, respectively).

Conclusion

The levels of VEGF and other cytokines changed in the vitreous after IVB. The adverse effects associated with IVB, such as fibrosis, may result from modulation of vitreous cytokine concentrations. In the treatment of PDR, drugs that optimize the effects of PIGF, IGF-1, and VE-cadherin to reduce these side effects may be useful.

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Data availability

The data that support the findings of this study are available from the corresponding author, (F.O.), upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

The authors are grateful to Mr Jeremy Jones of the Academic Writing Department of Kocaeli University, Izmit, Turkey, for his English editing of the text and his advice concerning the contents of this manuscript. The authors thank Dr. Emrah Gokay Ozgur, Department of Biostatistics and Medical Informatics, Faculty of Medicine, University of Kocaeli, for her assistance during the statistical analysis.

Funding

This study was funded by Kocaeli University Scientific Research Project Coordination Unit (KOU-BAP: Project No: TTU-2020-2117). The sponsor had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Ophthalmology, Kocaeli University Medical School, 41001, İzmit, Kocaeli, Turkey

    Fevzi Ozer & Veysel Levent Karabas

  2. Department of Ophthalmology, Kocaeli Derince Training and Research Hospital, İzmit, Turkey

    Ecem Onder Tokuc

  3. Department of Medical Biology, Kocaeli University Medical School, İzmit, Turkey

    Merve Gulsen Bal Albayrak, Gurler Akpinar & Murat Kasap

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  1. Fevzi Ozer
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Correspondence to Fevzi Ozer.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Informed consent was obtained from all individual participants included in the study. Approval was obtained from the ethics committee of Kocaeli University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Ozer, F., Tokuc, E.O., Albayrak, M.G.B. et al. Comparison of before versus after intravitreal bevacizumab injection, growth factor levels and fibrotic markers in vitreous samples from patients with proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 260, 1899–1906 (2022). https://doi.org/10.1007/s00417-021-05515-3

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