Vitreous VEGF levels among patients with proliferative diabetic retinopathy depending on the general clinical status and ocular status
Vira S. Ponomarchuk, L. M. Velychko, M. M. Umanets
SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine»; Odesa (Ukraine)
Background: The most common cause of visual impairment in patients with diabetic retinopathy is the pathology progression to the proliferative stage which is accompanied by apparent fibrovascular proliferation, development of tractional retinal detachment and/or vitreous hemorrhage. Vascular endothelial growth factor (VEGF) is the most important in the pathogenesis of ocular microvascular changes in diabetes.
Purpose: To assess vitreous VEGF levels in the proliferative diabetic retinopathy (PDR) patients not initially treated with anti-VEGF agents, depending on the general clinical status and ocular status.
Material and Methods: Forty-one patients (45 eyes) aged 19 to 81 years with neovascular glial PDR and epiretinal membrane with a marked proliferative component were involved in the study. Each patient underwent a 25G three-port vitrectomy during which a vitreous specimen was collected. Vitreous VEGF levels were determined by a three-step enzyme-linked immunosorbent assay.
Results: We managed to assess total vitreous VEGF levels in 44 of the 45 eyes. Patients with PDR had elevated total vitreous VEGF levels, with a mean value of 757.69 ± 117 pg/ml, confirming the involvement of VEGF in pathological intraocular angiogenesis. There was a significant difference in vitreous VEGF levels between PDR patients with a fibrovascular membrane with a marked proliferative component (997.0±151.8 pg/ml) and those with a fibrovascular membrane with a moderate proliferative component (244.9 ± 53.7 pg/ml) (F = 10.3; р = 0.0025).
Keywords: vascular endothelial growth factor, proliferative diabetic retinopathy
1.Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376:124–136.
2.Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004 Aug;25(4):581-611. doi: 10.1210/er.2003-0027.
3.Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264.
4.Agarwal D, Gelman R, Prospero Ponce C, et al. Vitreomacular Interface in Diabetic Retinopathy. J Ophthalmol. 2015;2015:392983. doi: 10.1155/2015/392983..
5.Schlingemann RO, van Hinsbergh VW. Role of vascular permeability factor / vascular endothelial growth factor in eye disease. Br J Ophthalmol. 1997 Jun;81(6):501-12. doi: 10.1136/bjo.81.6.501.
6.Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983-5. doi: 10.1126/science.6823562.
7.Bhisitkul RB. Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol. 2006 Dec;90(12):1542-7. doi: 10.1136/bjo.2006.098426.
8.Levy NS, Chung S, Furneaux H, et al. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem. 1998 Mar 13;273(11):6417-23. doi: 10.1074/jbc.273.11.6417.
9.Adamis AP, Shima DT, Yeo KT, et al. Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem Biophys Res Commun. 1993 Jun 15;193(2):631-8. doi: 10.1006/bbrc.1993.1671.
10.Aiello LP, Northrup JM, Keyt BA, et al. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol. 1995 Dec;113(12):1538-44.. doi: 10.1001/archopht.1995.01100120068012.
11.Ferrara N, Gerber HP, LeCouter JN. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669-76. doi: 10.1038/nm0603-669.
12.Takahashi H, Shibuya M.. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond). 2005 Sep;109(3):227-41. doi: 10.1042/CS20040370.
13.Gilbert RE, Vranes D, Berka JL, et al. Vascular endothelial growth factor and its receptors in control and diabetic rat eyes. Lab In-vest. - 1998 Aug;78(8):1017-27.
14.Murata T, Nakagawa K, Khalil A, et al. The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas. Lab Invest. 1996 Apr;74(4):819-25..
15.Neroev VV, Zaytseva OV, Balatskaya NV, Kurchaeva ZV. [Local and systemic VEGF-A production in complicated proliferated diabetic retinopathy]. Meditsinskaya immunologiya. 2016;18(4):357-64. Russian. doi: 10.15789/1563-0625-2016-4-357-364.
16.Chen HJ, Ma Z-Z, Li Y, et al. Change of Vascular Endothelial Growth Factor Levels following Vitrectomy in Eyes with Prolifera-tive Diabetic Retinopathy. J Ophthalmol. 2019 Oct 23;2019:6764932. doi: 10.1155/2019/6764932.
17.Muhiddin HS, Kamaruddin MI, Ichsan AM, et al. Vitreous and Serum Concentrations of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor in Proliferative Diabetic Retinopathy. Clin Ophthalmol. 2020 Jun 9;14:1547-1552. doi: 10.2147/OPTH.S248812.
18.Pasyechnikova NV. [Laser treatment in fundus diseases]. Kyiv: Naukova dumka; 2007. Russian.
19.Sakamoto M, Hashimoto R, Yoshida I, et al. Risk factors for neovascular glaucoma after vitrectomy in eyes with proliferative dia-betic retinopathy. Clin Ophthalmol. 2018 Nov 14;12:2323-2329. doi: 10.2147/OPTH.S184959.
20.Kadonosono K, Matsumoto S, Uchio E, et al. Iris neovascularization after vitrectomy combined with phacoemulsification and intra-ocular lens implantation for proliferative diabetic retinopathy. Ophthalmic Surg Lasers. Jan-Feb 2001;32(1):19-24.
21.Tojo N, Kashiwagi Y, Nishitsuka K, et al. Interactions between vitreous-derived cells and vascular endothelial cells in vitreoretinal diseases. Acta Ophthalmologica. Acta Ophthalmologica. 88(5):564-70. DOI: 10.1111/j.1755-3768.2008.01466.x.
22.Kocak N, Alacacioglu I, Kaynak S, et al. Comparison of vitreous and plasma levels of vascular endothelial growth factor, interleu-kin-6 and hepatocyte growth factor in diabetic and non-diabetic retinal detachment cases. Ann Ophthalmol (Skokie). 2010;42 Spec No:10-4.
23.Kabesha TB, Glacet-Bernard A, Rostaqui O, et al. [Anti-VEGF therapy in the treatment of anterior segment neovascularization sec-ondary to central retinal vein occlusion]. J Fr Ophtalmol. 2015 May;38(5):414-20. doi: 10.1016/j.jfo.2014.11.007.
24.Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopa-thy. Am J Ophthalmol. 1994 Oct 15;118(4):445-50. doi: 10.1016/s0002-9394(14)75794-0.
25.Lip PL, Belgore F, Blann AD, et al. Plasma VEGF and soluble VEGF receptor FLT-1 in proliferative retinopathy: relationship to endothelial dysfunction and laser treatment. Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2115-9.
26.Mohamed TA, Mohamed Sel-D. Effect of pan-retinal laser photocoagulation on plasma VEGF, endothelin-1 and nitric oxide in PDR. Int J Ophthalmol. 2010;3(1):19-22. doi: 10.3980/j.issn.2222-3959.2010.01.05.
27.Neroev VV, Slepova OS, Zaitseva OV. [Features of local and systemic endothelin production in complicated proliferated diabetic retinopathy]. Rossiiskii oftalmologicheskii zhurnal. 2015;8(3):31-7. Russian.
Conflict of Interest Statement:
The authors declare no conflict of interest which could influence their opinions on the subject or the materials presented in the manuscript.