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Review
. 2020 Feb 6;2(2):CD007920.
doi: 10.1002/14651858.CD007920.pub3.

Anti-vascular endothelial growth factor for neovascular glaucoma

Arathi Simha  1 , Kanza Aziz  2 , Andrew Braganza  1 , Lekha Abraham  1 , Prasanna Samuel  3 , Kristina B Lindsley  4
Affiliations
Review

Anti-vascular endothelial growth factor for neovascular glaucoma

Arathi Simha et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG.

Objectives: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG.

Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials.

Selection criteria: We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG.

Data collection and analysis: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion.

Main results: We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up.

Authors' conclusions: Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.

PubMed Disclaimer

Conflict of interest statement

Arathi Simha: none known Kanza Aziz: none known Andrew Braganza: none known Lekha Abraham: none known Prasanna Samuel: none known Kristina Lindsley: none known

Figures

1
1
Flowchart showing results from literature search
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 Anti‐VEGF medications vs no anti‐VEGF medications, Outcome 1 Mean intraocular pressure.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Arcieri 2015 {published data only}
    1. ACTRN12607000577415. Efficacy and safety of intravitreal avastin in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82392 (first received 4 November 2007).
    1. Arcieri ES, Paula JS, Jorge R, Barella KA, Arcieri RS, Secches DJ, et al. Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2‐year follow‐up. Acta Ophthalmologica 2015;93(1):e1‐6. - PubMed
    1. Arcieri ES, Secches DJL, Paula JS, Barella KA, Arcieri RS, Jorge R, et al. Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation ‐ preliminary report. ARVO. 2010:627/A471. - PubMed
Jiang 2015 {published data only}
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Mahdy 2013 {published data only}
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NCT02396316 {published data only}
    1. NCT02396316. Japanese phase 3 study of aflibercept in neovascular glaucoma patients. clinicaltrials.gov/ct2/show/NCT02396316 (first received 24 March 2015).

References to studies excluded from this review

Bodla 2017 {published data only}
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ChiCTR‐IPR‐15006695 {published data only}
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Costagliola 2008 {published data only}
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EUCTR2007‐000585‐21‐IE {published data only}
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Gupta 2009 {published data only}
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    1. Gupta V, Jha R, Rao A, Kong G, Sihota R. The effect of different doses of intracameral bevacizumab on surgical outcomes of trabeculectomy for neovascular glaucoma. European Journal of Ophthalmology 2009;19(3):435‐41. - PubMed
Jonas 2010 {published data only}
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Kong 2017 {published data only}
    1. Kong F, Ma X, Fan S, Lu J, Qin X, Zou J. Efficacy of intravitreal lucentis or conbercept injection combined with Ahmed glaucoma valve implantation for treatment of neovascular glaucoma. Journal of Jilin University (Medicine Edition) 2017;43(6):1237‐42.
Lin 2018 {published data only}
    1. Lin N, Zheng WD, Li B. Clinical effect of ranibizumab combined with PPV on PDR with neovascular glaucoma at early stage. International Eye Science 2018;18(2):294‐7.
Miki 2011 {published data only}
    1. Miki A, Oshima Y, Otori Y, Matsushita K, Nishida K. One‐year results of intravitreal bevacizumab as an adjunct to trabeculectomy for neovascular glaucoma in eyes with previous vitrectomy. Eye 2011;25(5):658‐9. - PMC - PubMed
NCT01128699 {unpublished data only}
    1. NCT01128699. Ahmed valve glaucoma implant with adjunctive subconjunctival bevacizumab in refractory glaucoma. clinicaltrials.gov/ct2/show/NCT01128699 (first received 24 May 2010).
NCT01711879 {unpublished data only}
    1. NCT01711879. Use of intravitreal aflibercept injection for neovascular glaucoma. clinicaltrials.gov/ct2/show/NCT01711879 (first received 22 October 2012).
NCT03154892 {published data only}
    1. NCT03154892. The effect of conbercept injection through different routes for neovascular glaucoma. clinicaltrials.gov/ct2/show/NCT03154892 (first received 16 May 2017).
Sedghipour 2011 {published data only}
    1. Sedghipour MR, Mostafaei A, Taghavi Y. Low‐dose subconjunctival bevacizumab to augment trabeculectomy for glaucoma. Clinical Ophthalmology 2011;5(1):797‐800. - PMC - PubMed
Silva 2006 {published data only}
    1. Silva Paula J, Jorge R, Alves Costa R, Rodrigues Mde L, Scott IU. Short‐term results of intravitreal bevacizumab (Avastin) on anterior segment neovascularization in neovascular glaucoma. Acta Ophthalmologica Scandinavica 2006;84(4):556‐7. - PubMed
Wang 2016 {published data only}
    1. Wang F, Wang LL. Safety of anti‐VEGF drugs with trabeculectomy for neovascular glaucoma. International Eye Science 2016;16(5):837‐40.
Wittstrom 2012 {published data only}
    1. Wittstrom E, Holmberg H, Hvarfner C, Andreasson S. Clinical and electrophysiologic outcome in patients with neovascular glaucoma treated with and without bevacizumab. European Journal of Ophthalmology 2012;22(4):563‐74. - PubMed
Yazdani 2009 {published data only}
    1. Yazdani S, Hendi K, Pakravan M, Mahdavi M, Yaseri M. Intravitreal bevacizumab for neovascular glaucoma: a randomized controlled trial. Journal of Glaucoma 2009;18(8):632‐7. - PubMed

References to ongoing studies

NCT02914626 {unpublished data only}
    1. NCT02914626. Intravitreal ranibizumab (Lucentis®) for neovascular glaucoma ‐ a randomized controlled study. clinicaltrials.gov/ct2/show/NCT02914626 (first received 26 September 2016).

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References to other published versions of this review

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