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Serum and vitreous vascular endothelial growth factor levels in diabetic retinopathy

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Abstract

Purpose

To research whether serum vascular endothelial growth factor (VEGF) levels could be used to evaluate diabetic retinopathy (DR) progression and to compare vitreous VEGF levels after injections of intravitreal bevacizumab (IVB), ranibizumab (IVR), and triamcinolone acetonide (IVTA) in proliferative diabetic retinopathy (PDR).

Methods

We enrolled a total of 91 eyes of 89 subjects (70 eyes of 68 diabetics and 21 eyes of 21 non-diabetic controls). The diabetic subjects were divided into three groups as PDR (n = 28), non-proliferative diabetic retinopathy (n = 20), and no-DR (n = 20). Eyes with PDR (n = 31) were injected with IVB (n = 7), IVR (n = 10), or IVTA (n = 6) 3 days before vitrectomy, and eight eyes did not receive an injection. Serum and vitreous samples were collected before vitrectomy and analyzed using ELISA.

Results

We found the severity of retinopathy was not correlated with serum VEGF levels (P = .919, ρ = −0.011). Compared with the controls, vitreous VEGF was higher in the PDR (P < .001), whereas serum VEGF did not differ (P = .99). The controls had lower vitreous VEGF than the IVB, IVR, and no-injection subgroups (P = .01, P < .001, and P = .04, respectively). Vitreous VEGF was similar among the injected and no-injection subgroups (P = .17).

Conclusions

Serum VEGF levels may not directly reflect retinopathy progression. Neither IVB, IVR nor IVTA could eliminate vitreous VEGF levels within 3 days before vitrectomy.

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References

  1. Cheung N, Mitchell P, Wong TY (2010) Diabetic retinopathy. Lancet 376(9735):124–136. https://doi.org/10.1016/S0140-6736(09)62124-3

    Article  PubMed  Google Scholar 

  2. Wong TY, Cheung CM, Larsen M et al (2016) Diabetic retinopathy. Nat Rev Dis primers 2:16012. https://doi.org/10.1038/nrdp.2016.12

    Article  PubMed  Google Scholar 

  3. Liu L, Wu X, Liu L et al (2012) Prevalence of diabetic retinopathy in mainland China: a meta-analysis. PLoS ONE 7(9):e45264. https://doi.org/10.1371/journal.pone.0045264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Watanabe D, Suzuma K, Suzuma I et al (2005) Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Am J Ophthalmol 139(3):476–481. https://doi.org/10.1016/j.ajo.2004.10.004

    Article  CAS  PubMed  Google Scholar 

  5. Baharivand N, Zarghami N, Panahi F et al (2012) Relationship between vitreous and serum vascular endothelial growth factor levels, control of diabetes and microalbuminuria in proliferative diabetic retinopathy. Clin Ophthalmol 6:185–191. https://doi.org/10.2147/OPTH.S27423

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wu R, Zhu Z, Zhou D (2020) VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis. BMC Ophthalmol 20(1):326. https://doi.org/10.1186/s12886-020-01593-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Praidou A, Klangas I, Papakonstantinou E et al (2009) Vitreous and serum levels of platelet-derived growth factor and their correlation in patients with proliferative diabetic retinopathy. Curr Eye Res 34(2):152–161. https://doi.org/10.1080/02713680802585920

    Article  CAS  PubMed  Google Scholar 

  8. Arevalo JF, Lasave AF, Kozak I et al (2019) Preoperative bevacizumab for tractional retinal detachment in proliferative diabetic retinopathy: a prospective randomized clinical trial. Am J Ophthalmol 207:279–287. https://doi.org/10.1016/j.ajo.2019.05.007

    Article  CAS  PubMed  Google Scholar 

  9. Zhang ZH, Liu HY, Hernandez-Da Mota SE et al (2013) Vitrectomy with or without preoperative intravitreal bevacizumab for proliferative diabetic retinopathy: a meta-analysis of randomized controlled trials. Am J Ophthalmol 156(1):106–115. https://doi.org/10.1016/j.ajo.2013.02.008

    Article  CAS  PubMed  Google Scholar 

  10. Hu L, Chen Q, Du Z et al (2021) Evaluation of vitrectomy combined preoperative intravitreal ranibizumab and postoperative intravitreal triamcinolone acetonide for proliferative diabetic retinopathy. Int Ophthalmol 41(5):1635–1642. https://doi.org/10.1007/s10792-021-01703-6

    Article  PubMed  Google Scholar 

  11. Brooks HL Jr, Caballero S Jr, Newell CK et al (2004) Vitreous levels of vascular endothelial growth factor and stromal-derived factor 1 in patients with diabetic retinopathy and cystoid macular edema before and after intraocular injection of triamcinolone. Arch Ophthalmol 122(12):1801–1807. https://doi.org/10.1001/archopht.122.12.1801

    Article  CAS  PubMed  Google Scholar 

  12. Klein R, Klein BE, Moss SE et al (1984) The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 102(4):527–532. https://doi.org/10.1001/archopht.1984.01040030405011

    Article  CAS  PubMed  Google Scholar 

  13. Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification (1991) ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 98(5 Suppl):786–806

  14. Arimura N, Otsuka H, Yamakiri K et al (2009) Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy. Ophthalmology 116(5):921–926. https://doi.org/10.1016/j.ophtha.2008.12.024

    Article  PubMed  Google Scholar 

  15. Zhou Z, Ju H, Sun M et al (2019) Serum vascular endothelial growth factor levels correlate with severity of retinopathy in diabetic patients: a systematic review and meta-analysis. Dis Markers 2019:9401628. https://doi.org/10.1155/2019/9401628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ozturk BT, Bozkurt B, Kerimoglu H et al (2009) Effect of serum cytokines and VEGF levels on diabetic retinopathy and macular thickness. Mol Vis 15:1906–1914

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee IG, Chae SL, Kim JC (2006) Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy. Eye (London) 20(5):546–552. https://doi.org/10.1038/sj.eye.6701920

    Article  CAS  Google Scholar 

  18. Ang WJ, Zunaina E, Norfadzillah AJ et al (2019) Evaluation of vascular endothelial growth factor levels in tears and serum among diabetic patients. PLoS ONE 14(8):e0221481. https://doi.org/10.1371/journal.pone.0221481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Simo R, Lecube A, Segura RM et al (2002) Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. Am J Ophthalmol 134(3):376–382. https://doi.org/10.1016/s0002-9394(02)01538-6

    Article  CAS  PubMed  Google Scholar 

  20. Wu F, Phone A, Lamy R et al (2020) Correlation of aqueous, vitreous, and plasma cytokine levels in patients with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 61(2):26. https://doi.org/10.1167/iovs.61.2.26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S et al (2018) Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases. Growth Factors 36(1–2):48–57. https://doi.org/10.1080/08977194.2018.1477140

    Article  CAS  PubMed  Google Scholar 

  22. Wang J, Chen S, Jiang F et al (2014) Vitreous and plasma VEGF levels as predictive factors in the progression of proliferative diabetic retinopathy after vitrectomy. PLoS ONE 9(10):e110531. https://doi.org/10.1371/journal.pone.0110531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li B, Li MD, Ye JJ et al (2020) Vascular endothelial growth factor concentration in vitreous humor of patients with severe proliferative diabetic retinopathy after intravitreal injection of conbercept as an adjunctive therapy for vitrectomy. Chin Med J 6:664–669. https://doi.org/10.1097/CM9.0000000000000687

    Article  CAS  Google Scholar 

  24. Keles A, Sonmez K, Erol YO et al (2020) Vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1alpha, and angiopoietin-like protein 2 in patients with active proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. https://doi.org/10.1007/s00417-020-04889-0

    Article  PubMed  Google Scholar 

  25. Burgos R, Simo R, Audi L et al (1997) Vitreous levels of vascular endothelial growth factor are not influenced by its serum concentrations in diabetic retinopathy. Diabetologia 40(9):1107–1109. https://doi.org/10.1007/s001250050794

    Article  CAS  PubMed  Google Scholar 

  26. Muhiddin HS, Kamaruddin MI, Ichsan AM et al (2020) Vitreous and serum concentrations of vascular endothelial growth factor and platelet-derived growth factor in proliferative diabetic retinopathy. Clin Ophthalmol 14:1547–1552. https://doi.org/10.2147/OPTH.S248812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Feng J, Li B, Wen J et al (2018) Preoperative timing of intravitreal bevacizumab injection for proliferative diabetic retinopathy patients. Ophthalmic Res 60(4):250–257. https://doi.org/10.1159/000493640

    Article  CAS  PubMed  Google Scholar 

  28. Ma Y, Zhang Y, Zhao T et al (2012) Vascular endothelial growth factor in plasma and vitreous fluid of patients with proliferative diabetic retinopathy patients after intravitreal injection of bevacizumab. Am J Ophthalmol 153(2):307–313. https://doi.org/10.1016/j.ajo.2011.08.006

    Article  CAS  PubMed  Google Scholar 

  29. Qian J, Lu Q, Tao Y et al (2011) Vitreous and plasma concentrations of apelin and vascular endothelial growth factor after intravitreal bevacizumab in eyes with proliferative diabetic retinopathy. Retina 31(1):161–168. https://doi.org/10.1097/IAE.0b013e3181e46ad8

    Article  CAS  PubMed  Google Scholar 

  30. Yan Y, Zhu L, Hong L et al (2016) The impact of ranibizumab on the level of intercellular adhesion molecule type 1 in the vitreous of eyes with proliferative diabetic retinopathy. Acta Ophthalmol 94(4):358–364. https://doi.org/10.1111/aos.12806

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This project was supported by the Marmara University Scientific Research Projects Committee (BAPKO) (SAG-C-TUP-121114-0356). The authors declare that there is no conflict of interest. This study was partly presented as a poster at the 68th Annual Scientific Meeting of the American Association for Clinical Chemistry in Philadelphia, PA, USA, held July 31–August 4, 2016, and at the 19th Congress of the European Association for Vision and Eye Research in Nice, France, held October 5–8, 2016.

Funding

This study was supported by the Marmara University Scientific Research Projects Committee (BAPKO) (Grant number SAG-C-TUP-121114-0356). Author Osman Cekic has received research support from BAPKO.

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Authors and Affiliations

  1. Department of Ophthalmology, Marmara University School of Medicine, Istanbul, Turkey

    Fatma Isil Sozen-Delil & Osman Cekic

  2. Department of Biochemistry, Marmara University School of Medicine, Istanbul, Turkey

    Goncagul Haklar

Authors
  1. Fatma Isil Sozen-Delil
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  2. Osman Cekic
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Contributions

S-D and C designed the study. C performed the operations. H worked on biochemical analyses. S-D wrote the main manuscript text. S-D prepared tables. All authors (S-D, C, and H) analyzed and reviewed the manuscript.

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Correspondence to Fatma Isil Sozen-Delil.

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Sozen-Delil, F.I., Cekic, O. & Haklar, G. Serum and vitreous vascular endothelial growth factor levels in diabetic retinopathy. Int Ophthalmol 43, 2247–2255 (2023). https://doi.org/10.1007/s10792-022-02620-y

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