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Review
. 2024 Jul 29;17(8):1000.
doi: 10.3390/ph17081000.

Off-Label Use of Bevacizumab in Patients Diagnosed with Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

João Estarreja  1 , Priscila Mendes  1 , Carina Silva  1   2 , Pedro Camacho  1 , Vanessa Mateus  1   3
Affiliations
Review

Off-Label Use of Bevacizumab in Patients Diagnosed with Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

João Estarreja et al. Pharmaceuticals (Basel). .

Abstract

Background: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly people. Current pharmacological treatment in vascular AMD includes anti-VEGF agents, such as ranibizumab and aflibercept. Additionally, the off-label use of bevacizumab has been shown to be effective and has a lower cost, making it an interesting pharmacological approach; however, there is no consensus about its use. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy, safety, and efficiency of bevacizumab in AMD patients.

Methods: This review only focused on randomized controlled clinical trials published in 2010 in the MEDLINE database that compared the effect of bevacizumab with ranibizumab. The risk of bias in each included study was assessed using the CASP Randomised Clinical Trials checklist.

Results: Twelve studies were included for qualitative synthesis, and nine of them were considered for meta-analysis. Bevacizumab-treated patients showed a significantly reduced neovascularization in a longer spectrum of time; however, they had a higher incidence of endophthalmitis than those treated with ranibizumab. Regarding efficiency, the mean number of administrations was reduced in the treatment with bevacizumab in comparison to ranibizumab.

Conclusions: Clinical evidence demonstrates that bevacizumab has efficacy and safety profiles comparable with ranibizumab; however, it is relatively more efficient.

Keywords: AMD; age-related macular degeneration; bevacizumab; drug therapy; nAMD; neovascular age-related macular degeneration; wet macular degeneration.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram representing the process of study selection for qualitative and quantitative syntheses.
Figure 2
Figure 2
Forest plots representing the efficacy outcomes regarding treatments with bevacizumab and ranibizumab. Legend: (A) visual acuity; (B) retinal thickness; (C) fovea thickness. Legend: Chakravarthy et al. (2015) [31] study was analyzed considering both 1-year and 2-year (*) treatment outcomes. Martin et al. (2012) [37] study was evaluated considering both monthly and “as needed” (*) treatment protocols [29,30,31,32,35,37].
Figure 3
Figure 3
Forest plot representing efficacy outcomes of neovascularization regarding the treatment with bevacizumab and ranibizumab. Legend: (A), fluid on OCT; (B), dye leakage in FA; (C), subgroup analysis for dye leakage in FA. Chakravarthy et al. (2015) [31] study was analyzed considering both 1-year and 2-year (*) treatment outcomes [29,30,31,32,35].
Figure 4
Figure 4
Forest plots representing the ocular safety outcomes regarding the treatment with bevacizumab and ranibizumab. Legend: (A) endophthalmitis; (B) pseudoendophthalmitis; (C) hemorrhage, either conjunctival or subconjunctival [28,29,31,32,34,35,36,37,39].
Figure 4
Figure 4
Forest plots representing the ocular safety outcomes regarding the treatment with bevacizumab and ranibizumab. Legend: (A) endophthalmitis; (B) pseudoendophthalmitis; (C) hemorrhage, either conjunctival or subconjunctival [28,29,31,32,34,35,36,37,39].
Figure 5
Figure 5
Forest plots representing the systemic safety outcomes regarding the treatment with bevacizumab and ranibizumab. Legend: (A) serious systemic events; (B) cardiovascular disorders; (C) vascular abnormalities; (D) infection; (E) benign or malignant neoplasm. Chakravarthy et al. (2015) [31] study was analyzed considering both 1-year and 2-year (*) treatment outcomes [28,29,30,31,32,34,35,36,37,39].
Figure 5
Figure 5
Forest plots representing the systemic safety outcomes regarding the treatment with bevacizumab and ranibizumab. Legend: (A) serious systemic events; (B) cardiovascular disorders; (C) vascular abnormalities; (D) infection; (E) benign or malignant neoplasm. Chakravarthy et al. (2015) [31] study was analyzed considering both 1-year and 2-year (*) treatment outcomes [28,29,30,31,32,34,35,36,37,39].
Figure 6
Figure 6
Forest plot representing the incidence of injury or procedural complications during the treatment with bevacizumab and ranibizumab [28,29,30,31,32,34,35,36,37].
Figure 7
Figure 7
Forest plot representing the mean number of administrations regarding the treatment with bevacizumab and ranibizumab. Legend: Chakravarthy et al. (2015) [31] study was analyzed considering both 1-year and 2-year (*) treatment outcomes. Martin et al. (2012) [37] study was evaluated considering both monthly and “as needed” (*) treatment protocols [28,29,31,32,34,35,36,37].
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