Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) as an Adjuvant Before Vitrectomy for Proliferative Diabetic Retinopathy (PDR)
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Introduction: The primary treatment in proliferative diabetic retinopathy (PDR) is vitrectomy; however, direct intervention to the dense proliferative fibrovascular membrane may lead to massive hemorrhage obscuring the surgery process. Purpose: to review the use of anti-vascular endothelial growth factor (VEGF) as an adjuvant therapy before pars plana vitrectomy in PDR cases. Review: Anti-VEGF has been proposed as an adjuvant preceding the vitrectomy to lower intraoperative and post-operative complications. On the other hand, it could increase fibrosis which triggers tractional retinal detachment (TRD) in PDR cases. Conclusion: Intervals of five to ten days are considered the most ideal between anti-VEGF injection and pars plana vitrectomy (PPV) surgery in which the adjuvant therapy has made neovascularization regression and before the occurrence of fibrovascular contractions.
McCannel CA, Berrocal AM, Holder GE, Kim SJ, Leonard BC, Rosen RB, et al., editors. Retina and Vitreous Print. 2020-2021 Basic Clinical Science Course, San Francisco: American Academy of Ophthalmology; 2020.
World Health Organization. World Report on Vision. Geneva: 2019.
Kanski JJ, Bowling B, Nischal KK, Pearson A. Clinical Ophthalmology: A Systematic Approach. 9th ed. Edinburgh: Elsevier; 2019.
Miron L, Gafton B, Marinca M. Angiogeneza tumorala - implicatii in terapia cancerelor. Jurnalul Chir 2010;6:104–111.
Melincovici CS, Bosca AB, Susman S, Marginean M, Mihu C, Istrate M, et al. Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol 2018;59:455–467.
Bek T. Diameter changes of retinal vessels in diabetic retinopathy. Curr Diab Rep 2017;17:82. https://doi.org/10.1007/s11892-017-0909-9.
Naruse K, Nakamura J, Hamada Y, Nakayama M, Chaya S, Komori T, et al. Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes. Exp Eye Res 2000;71:309–315. https://doi.org/10.1006/exer.2000.0882.
Romeo G, Liu W-H, Asnaghi V, Kern TS, Lorenzi M. Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes 2002;51:2241–2248. https://doi.org/10.2337/diabetes.51.7.2241.
Ejaz S, Chekarova I, Ejaz A, Sohail A, Lim CW. Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes Obes Metab 2008;10:53–63. https://doi.org/10.1111/j.1463-1326.2007.00795.x.
Wang W, Lo ACY. Diabetic retinopathy: Pathophysiology and treatments. Int J Mol Sci 2018;19. https://doi.org/10.3390/ijms19061816.
Tien T, Zhang J, Muto T, Kim D, Sarthy VP, Roy S. High glucose induces mitochondrial dysfunction in retinal müller cells: Implications for diabetic retinopathy. Invest Ophthalmol Vis Sci 2017;58:2915–2921. https://doi.org/10.1167/iovs.16-21355.
Sohn EH, van Dijk HW, Jiao C, Kok PHB, Jeong W, Demirkaya N, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A 2016;113:E2655-64. https://doi.org/10.1073/pnas.1522014113.
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813–820. https://doi.org/10.1038/414813a.
Romero-Aroca P, Baget-Bernaldiz M, Pareja-Rios A, Lopez-Galvez M, Navarro-Gil R, Verges R. Diabetic macular edema pathophysiology: Vasogenic versus Inflammatory. J Diabetes Res 2016;2016:2156273. https://doi.org/10.1155/2016/2156273.
Mao J-B, Wu H-F, Chen Y-Q, Zhao S-X, Tao J-W, Zhang Y, et al. Effect of intravitreal conbercept treatment before vitrectomy in proliferative diabetic retinopathy. Int J Ophthalmol 2018;11:1217–1221. https://doi.org/10.18240/ijo.2018.07.23.
Faisal SM, Tahir MA, Cheema AM, Anjum MI. Pars plana vitrectomy in vitreous hemorrhage with or without intravitreal bevacizumab a comparative overview. Pakistan J Med Sci 2018;34:221–225. https://doi.org/10.12669/pjms.341.12683.
Zhao X-Y, Xia S, Chen Y-X. Antivascular endothelial growth factor agents pretreatment before vitrectomy for complicated proliferative diabetic retinopathy: A meta-analysis of randomised controlled trials. Br J Ophthalmol 2018;102:1077–1085. https://doi.org/10.1136/bjophthalmol-2017-311344.
Kamura Y, Sato Y, Deguchi Y, Yagi F. Iatrogenic retinal breaks during 20-gauge vitrectomy for proliferative diabetic retinopathy. Clin Ophthalmol 2013;7:29–33. https://doi.org/10.2147/OPTH.S38784.
Rizzo S, Genovesi-Ebert F, Di Bartolo E, Vento A, Miniaci S, Williams G. Injection of intravitreal bevacizumab (avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefe's Arch Clin Exp Ophthalmol 2008;246:837–842. https://doi.org/10.1007/s00417-008-0774-y.
Yang C-M, Yeh P-T, Yang C-H, Chen M-S. Bevacizumab pretreatment and long-acting gas infusion on vitreous clear-up after diabetic vitrectomy. Am J Ophthalmol 2008;146:211–217. https://doi.org/10.1016/j.ajo.2008.04.028.
da R Lucena D, Ribeiro JAS, Costa RA, Barbosa JC, Scott IU, de Figueiredo-Pontes LL, et al. Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study). Br J Ophthalmol 2009;93:688–691. https://doi.org/10.1136/bjo.2008.151233.
Oshima Y, Shima C, Wakabayashi T, Kusaka S, Shiraga F, Ohji M, et al. Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. Ophthalmology 2009;116:927–938. https://doi.org/10.1016/j.ophtha.2008.11.005.
Modarres M, Nazari H, Falavarjani KG, Naseripour M, Hashemi M, Parvaresh MM. Intravitreal injection of bevacizumab before vitrectomy for proliferative diabetic retinopathy. Eur J Ophthalmol 2009;19:848–852. https://doi.org/10.1177/112067210901900526.
Gupta A, Bansal R, Gupta V, Dogra MR. Six-month visual outcome after pars plana vitrectomy in proliferative diabetic retinopathy with or without a single preoperative injection of intravitreal bevacizumab. Int Ophthalmol 2012;32:135–144. https://doi.org/10.1007/s10792-012-9541-5.
Manabe A, Shimada H, Hattori T, Nakashizuka H, Yuzawa M. Randomized controlled study of intravitreal bevacizumab 0.16 mg injected one day before surgery for proliferative diabetic retinopathy. Retina 2015;35:1800–1807. https://doi.org/10.1097/IAE.0000000000000577.
Witmer AN, Vrensen GFJM, Van Noorden CJF, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 2003;22:1–29. https://doi.org/10.1016/s1350-9462(02)00043-5.
Yang X, Xu J, Wang R, Mei Y, Lei H, Liu J, et al. A Randomized controlled trial of conbercept pretreatment before vitrectomy in proliferative diabetic retinopathy. J Ophthalmol 2016;2016:2473234. https://doi.org/10.1155/2016/2473234.
Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers 2006;10:515–527. https://doi.org/10.1007/s11030-006-9027-3.
Olsson A-K, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006;7:359–371. https://doi.org/10.1038/nrm1911.
Ferrara N. Vascular endothelial growth factor: Basic science and clinical progress. Endocr Rev 2004;25:581–611. https://doi.org/10.1210/er.2003-0027.
Ucuzian AA, Gassman AA, East AT, Greisler HP. Molecular mediators of angiogenesis. J Burn Care Res Off Publ Am Burn Assoc 2010;31:158–175. https://doi.org/10.1097/BCR.0b013e3181c7ed82.
Risau W. Mechanisms of angiogenesis. Nature 1997;386:671–674. https://doi.org/10.1038/386671a0.
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27–31. https://doi.org/10.1038/nm0195-27.
Qiu Y, Hoareau-Aveilla C, Oltean S, Harper SJ, Bates DO. The anti-angiogenic isoforms of VEGF in health and disease. Biochem Soc Trans 2009;37:1207–1213. https://doi.org/10.1042/BST0371207.
Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 2009;78:539–552. https://doi.org/10.1016/j.bcp.2009.04.029.
Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 2005;7:452–464. https://doi.org/10.1215/S1152851705000232.
Rosen LS. Clinical experience with angiogenesis signaling inhibitors: Focus on vascular endothelial growth factor (VEGF) blockers. Cancer Control 2002;9:36–44. https://doi.org/10.1177/107327480200902S05.
Ip MS, Domalpally A, Sun JK, Ehrlich JS. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology 2015;122:367–374. https://doi.org/10.1016/j.ophtha.2014.08.048.
Smith JM, Steel DH. Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy. Cochrane Database Syst Rev 2011:CD008214. https://doi.org/10.1002/14651858.CD008214.pub2.
Pakzad-Vaezi K, Albiani DA, Kirker AW, Merkur AB, Kertes PJ, Eng KT, et al. A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy. Ophthalmic Surg Lasers Imaging Retina 2014;45:521–524. https://doi.org/10.3928/23258160-20141118-06.
Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin epidemiologic study of diabetic retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 1998;105:1801–1815. https://doi.org/10.1016/S0161-6420(98)91020-X.
Nicholson BP, Schachat AP. A review of clinical trials of anti-VEGF agents for diabetic retinopathy. Graefe's Arch Clin Exp Ophthalmol 2010;248:915–930. https://doi.org/10.1007/s00417-010-1315-z.
El-Sabagh HA, Abdelghaffar W, Labib AM, Mateo C, Hashem TM, Al-Tamimi DM, et al. Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: Histopathologic findings and clinical implications. Ophthalmology 2011;118:636–641. https://doi.org/10.1016/j.ophtha.2010.08.038.
El-Batarny AM. Intravitreal bevacizumab as an adjunctive therapy before diabetic vitrectomy. Clin Ophthalmol 2008;2:709–716.
Beer PM, Wong SJ, Hammad AM, Falk NS, O'Malley MR, Khan S. Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth factor in two patients. Retina 2006;26:871–876. https://doi.org/10.1097/01.iae.0000233327.68433.02.
Comyn O, Wickham L, Charteris DG, Sullivan PM, Ezra E, Gregor Z, et al. Ranibizumab pretreatment in diabetic vitrectomy: A pilot randomised controlled trial (the RaDiVit study). Eye (Lond) 2017;31:1253–1258. https://doi.org/10.1038/eye.2017.75.
Farahvash M-S, Majidi AR, Roohipoor R, Ghassemi F. Preoperative injection of intravitreal bevacizumab in dense diabetic vitreous hemorrhage. Retina 2011;31:1254–1260. https://doi.org/10.1097/IAE.0b013e31820a68e5.
Ahn J, Woo SJ, Chung H, Park KH. The effect of adjunctive intravitreal bevacizumab for preventing postvitrectomy hemorrhage in proliferative diabetic retinopathy. Ophthalmology 2011;118:2218–2226. https://doi.org/10.1016/j.ophtha.2011.03.036.
Wei Q, Zhang T, Jiang R, Chang Q, Zhang Y, Huang X, et al. Vitreous fibronectin and fibrinogen expression increased in eyes with proliferative diabetic retinopathy after intravitreal anti-VEGF therapy. Invest Ophthalmol Vis Sci 2017;58:5783–5791. https://doi.org/10.1167/iovs.17-22345.
Arevalo JF, Maia M, Flynn HWJ, Saravia M, Avery RL, Wu L, et al. Tractional retinal detachment following intravitreal bevacizumab (avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol 2008;92:213–216. https://doi.org/10.1136/bjo.2007.127142.
Su L, Ren X, Wei H, Zhao L, Zhang X, Liu J, et al. Intravitreal conbercept (kh902) for surgical treatment of severe proliferative diabetic retinopathy. Retina 2016;36:938–943. https://doi.org/10.1097/IAE.0000000000000900.
Russo A, Longo A, Avitabile T, Bonfiglio V, Fallico M, Boscia F, et al. Incidence and risk factors for tractional macular detachment after anti-vascular endothelial growth factor agent pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. J Clin Med 2019;8. https://doi.org/10.3390/jcm8111960.
Castillo J, Aleman I, Rush SW, Rush RB. Preoperative bevacizumab administration in proliferative diabetic retinopathy patients undergoing vitrectomy: A randomized and controlled trial comparing interval variation. Am J Ophthalmol 2017;183:1–10. https://doi.org/10.1016/j.ajo.2017.08.013.
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