From the Hypotheses to Clinical Evidence in Retinal Therapy
The off-label, therapeutic use of intravitreal bevacizumab (IVB) in vascular retinal diseases such as diabetic macular edema and proliferative diabetic retinopathy (PDR) has increased significantly due to its ability to reduce retinal neovascularization and slow progression of disease. Here, we will review the literature and investigative developments on the use of IVB as a preoperative adjuvant to vitrectomy in severe PDR, specifically focusing on its ability to reduce intra- and postoperative complications and its risk for progression or development of traction retinal detachment. In particular, this review will highlight the natural progression of evidence from case series and observations to prospective, randomized clinical trials.
Diabetic Macular Edema, Diabetic Retinopathy, Intravitreal Bevacizumab, Tractional Retinal Detachment, Vascular Endothelial Growth Factor, Vitrectomy
1. Solomon SD, Chew E, Duh EJ, et al. Diabetic retinopathy: a position statement by the American Diabetes Association. Dia Care 2017;40:412–418.
2. Zhang X, Saaddine JB, Chou C-F, et al. Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA 2010;304:649.
3. Yau JWY, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012;35:556–564.
4. Adamis AP, Miller JW, Bernal M-T, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445–450.
5. Aiello LP, Avery RL, Arrigg PG, et al. Vascular Endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–1487.
6. Nicoletti V, Nicoletti R, Ferrara N, Meli G, Reibaldi M, Reibaldi A. Diabetic patients and retinal proliferation: an evaluation of the role of vascular endothelial growth factor (VEGF). Exp Clin Endocrinol Diabetes 2003;111:209–214.
7. Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA 2015;314:2137.
8. Sivaprasad S, Prevost AT, Vasconcelos JC, et al. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. Lancet 2017;389:2193–2203.
9. Sun JK, Glassman AR, Beaulieu WT, et al. Rationale and application of the protocol S anti–vascular endothelial growth factor algorithm for proliferative diabetic retinopathy. Ophthalmology 2019;126:87–95.
10. Chen E, Park CH. Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina 2006;26:699–700.
11. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113:1695– 1705.e6.
12. Zhao L-Q, Zhu H, Zhao P-Q, Hu Y-Q. A systematic review and meta-analysis of clinical outcomes of vitrectomy with or without intravitreal bevacizumab pretreatment for severe diabetic retinopathy. Br J Ophthalmol 2011;95:1216–1222.
13. Arevalo JF, Maia M, Flynn HW, et al. Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol 2008;92:213–216.
14. Jonas JB, Schmidbauer M, Rensch F. Progression of tractional retinal detachment following intravitreal bevacizumab. Acta Ophthalmol 2009;87:571–572.
15. Arevalo JF, Sanchez JG, Saldarriaga L, et al. Retinal detachment after bevacizumab. Ophthalmology 2011;118:2304.e3–2304.e7.
16. Arevalo JF, Lasave AF, Kozak I, et al. Preoperative bevacizumab for tractional retinal detachment in proliferative diabetic retinopathy: a prospective randomized clinical trial. Am J Ophthalmol 2019;207:279– 287.
17. Hutton D, Newman-Casey PA, Tavag M, Zacks D, Stein J. Switching to less expensive blindness drug could save medicare part b $18 billion over a ten-year period. Health Aff 2014;33:931–939.
18. Anothaisintawee T, Leelahavarong P, Ratanapakorn T, Teerawattananon. The use of comparative effectiveness research to inform policy decisions on the inclusion of bevacizumab for the treatment of macular diseases in Thailand’s pharmaceutical benefit package. CEOR 2012:361.
19. Grisanti S, Ziemssen F. Bevacizumab: off-label use in ophthalmology. Indian J Ophthalmol 2007;55:417.