Aim: The objective of this study was to evaluate the efficacy and safety of bevacizumab combined with antimetabolite as an adjunctive therapy in primary trabeculectomy for glaucoma. Materials and Methods: PubMed, Cochrane Library, and EMBASE were searched for relevant randomized controlled trials. Efficacy was evaluated by the postoperative mean intraocular pressure (IOP), complete success, and qualified success rates. Safety was evaluated by postoperative complications and surgical interventions. Results: A total of 3 randomized controlled trials were included in the meta-analysis. The primary outcome was postoperative mean IOP at the 12-month follow-up. No significant difference in IOP was found between the bevacizumab + antimetabolite (mitomycin c or 5-fluorouracil) group and the antimetabolite alone group (weighted mean difference –0.27; 95% CI –1.38 to 0.83). There were no significant differences in complete success rates, qualified success rates, postoperative complications, and surgical interventions between the experimental treatment group and the conventional treatment group. Conclusions: Results of the meta-analysis demonstrated that the combination of bevacizumab (1.25 mg/mL) with a regular concentration of antimetabolite did not show more benefit or harm compared with using antimetabolite alone. Further randomized controlled trials are needed to evaluate the efficacy and safety of bevacizumab combined with lower concentrations and a shorter application time of antimetabolite.

Keywords:
Glaucoma, Trabeculectomy, Bevacizumab, Mitomycin c, 5-Fluorouracil, Meta-analysis
1.
Resnikoff S, Pascolini D, Etya’ale D, et al: Global data on visual impairment in the year 2002. Bull World Health Organ 2004; 82: 844–851.
2.
Coleman AL, Miglior S: Risk factors for glaucoma onset and progression. Surv Ophthalmol 2008; 53(suppl 1):S3–S10.
3.
Rulli E, Biagioli E, Riva I, et al: Efficacy and safety of trabeculectomy vs nonpenetrating surgical procedures: a systematic review and meta-analysis. JAMA Ophthalmol 2013; 131: 1573–1582.
4.
Hitchings RA, Grierson I: Clinico pathological correlation in eyes with failed fistulizing surgery. Trans Ophthalmol Soc UK 1983; 103: 84–88.
5.
Addicks EM, Quigley HA, Green WR, et al: Histologic characteristics of filtering blebs in glaucomatous eyes. Arch Ophthalmol 1983; 101: 795–798.
6.
Yamamoto T, Varani J, Soong HK, et al: Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts. Ophthalmology 1990; 97: 1204–1210.
7.
Grewal DS, Jain R, Kumar H, et al: Evaluation of subconjunctival bevacizumab as an adjunct to trabeculectomy a pilot study. Ophthalmology 2008; 115: 2141–2145.
8.
Memarzadeh F, Varma R, Lin LT, et al: Post-operative use of bevacizumab as an antifibrotic agent in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci 2009; 50: 3233–3237.
9.
Fakhraie G, Ghadimi H, Eslami Y, et al: Short-term results of trabeculectomy using adjunctive intracameral bevacizumab: a randomized controlled trial. J Glaucoma 2016; 25:e182–e188.
10.
Kaushik J, Parihar JK, Jain VK, et al: Efficacy of bevacizumab compared to mitomycin c modulated trabeculectomy in primary open angle glaucoma: a one-year prospective randomized controlled study. Curr Eye Res 2017; 42: 217–224.
11.
Cheng JW, Cheng SW, Wei RL, et al: Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery. Cochrane Database Syst Rev 2016; 1:CD009782.
12.
Xiong Q, Li Z, Li Z, et al: Anti-VEGF agents with or without antimetabolites in trabeculectomy for glaucoma: a meta-analysis. PLoS One 2014; 9:e88403.
13.
Higgins JPT, et al: The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343:d5928.
14.
Higgins JPT, Altman DG: Assessing Risk of Bias in Included Studies; in Higgins JPT, Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions. Hoboken, John Wiley & Sons, 2008, pp 187–241.
15.
Vandewalle E, Abegao Pinto L, van Bergen T, et al: Intracameral bevacizumab as an adjunct to trabeculectomy: a 1-year prospective, randomised study. Br J Ophthalmol 2014; 98: 73–78.
16.
Kiddee W, Orapiriyakul L, Kittigoonpaisan K, et al: Efficacy of adjunctive subconjunctival bevacizumab on the outcomes of primary trabeculectomy with mitomycin c: a prospective randomized placebo-controlled trial. J Glaucoma 2015; 24: 600–606.
17.
Suh W, Kee C: The effect of bevacizumab on the outcome of trabeculectomy with 5-fluorouracil. J Ocul Pharmacol Ther 2013; 29: 646–651.
18.
Smith S, D’Amore PA, Dreyer EB: Comparative toxicity of mitomycin C and 5-fluorouracil in vitro. Am J Ophthalmol 1994; 118: 332–337.
19.
Zacharia PT, Deppermann SR, Schuman JS: Ocular hypotony after trabeculectomy with mitomycin C. Am J Ophthalmol 1993; 116: 314–326.
20.
Belyea DA, Dan JA, Stamper RL, et al: Late onset of sequential multifocal bleb leaks after glaucoma filtration surgery with 5-fluorouracil and mitomycin C. Am J Ophthalmol 1997; 124: 40–45.
21.
Wolner B, Liebmann JM, Sassani JW, et al: Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology 1991; 98: 1053–1060.
22.
Akkan JU, Cilsim S: Role of subconjunctival bevacizumab as an adjuvant to primary trabeculectomy: a prospective randomized comparative 1-year follow-up study. J Glaucoma 2015; 24: 1–8.
23.
Pro MJ, Freidl KB, Neylan CJ, et al: Ranibizumab versus mitomycin C in primary trabeculectomy – a pilot study. Curr Eye Res 2015; 40: 510–515.
24.
Nilforushan N, Yadgari M, Kish SK, et al: Subconjunctival bevacizumab versus mitomycin C adjunctive to trabeculectomy. Am J Ophthalmol 2012; 153: 352–357.
25.
Kahook MY: Bleb morphology and vascularity after trabeculectomy with intravitreal ranibizumab: a pilot study. Am J Ophthalmol 2010; 150: 399–403.
26.
Nissen NN, Polverini PJ, Koch AE, et al: Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 1998; 152: 1445–1452.
27.
Chua BE, Nguyen DQ, Qin Q, et al: Bleb vascularity following post-trabeculectomy sub-conjunctival bevacizumab: a pilot study. Clin Exp Ophthalmol 2012; 40: 773–779.
28.
Zahid S, Musch DC, Niziol LM, et al: Risk of endophthalmitis and other long-term complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS). Am J Ophthalmol 2013; 155: 674–680.
29.
Al-Haddad C, Abdulaal M, Al-Moujahed A, et al: Fornix-based versus limbal-based conjunctival trabeculectomy flaps for glaucoma. Cochrane Database Syst Rev 2015; 11: CD009380.
30.
Al-Haddad CE, Abdulaal M, Al-Moujahed A, et al: Fornix-based versus limbal-based conjunctival trabeculectomy flaps for glaucoma: findings from a cochrane systematic review. Am J Ophthalmol 2017; 174: 33–41.
31.
EI-Sayyad F, EI-Rashood A, Helal M, et al: Fornix-based versus limbal-based conjunctival flaps in initial trabeculectomy with postoperative 5-fluorouracil: four-year follow-up findings. J Glaucoma 1999; 8: 124–128.
32.
Bindlish R, Condon GP, Schlosser JD, et al: Efficacy and safety of mitomycin-C in primary trabeculectomy: five-year follow-up. Ophthalmology 2002; 109: 1336–1341.
33.
Kitazawa Y, Suemori-Matsushita H, Yamamoto T, et al: Low-dose and high-dose mitomycin trabeculectomy as an initial surgery in primary open-angle glaucoma. Ophthalmology 1993; 100: 1624–1628.
34.
Sanders SP, Cantor LB, Dobler AA, et al: Mitomycin C in higher risk trabeculectomy: a prospective comparison of 0.2- to 0.4-mg/cc doses. J Glaucoma 1999; 8: 193–198.
35.
Jampel HD: Effect of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon’s capsule fibroblasts. Ophthalmology 1992; 99: 1471–1476.
36.
Sihota R, Angmo D, Chandra A, et al: Evaluating the long-term efficacy of short-duration 0.1 and 0.2 mg/mL MMC in primary trabeculectomy for primary adult glaucoma. Graefes Arch Clin Exp Ophthalmol 2015; 253: 1153–1159.
37.
Kim YY, Sexton RM, Shin DH, et al: Outcomes of primary phakic trabeculectomies without versus with 0.5- to 1-min versus 3- to 5-min mitomycin C. Am J Ophthalmol 1998; 126: 755–762.
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2018
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