Anti-vascular endothelial growth factor for neovascular glaucoma

What was the aim of this review?
To compare treatment with and without anti-vascular endothelial growth factor (anti-VEGF) medications for people with neovascular glaucoma (NVG).

Key message
It is uncertain whether treatment with anti-VEGF medications is more beneficial than treatment without anti-VEGF medications for people with NVG. More research is needed to investigate the long-term effect of anti-VEGF medications compared with, or in addition to, conventional treatment.

What did we study in this review?
VEGF is a protein produced by cells in your body, and produces new blood vessels when needed. When cells produce too much VEGF, abnormal blood vessels can grow in the eye. NVG is a type of glaucoma where the angle between the iris (coloured part of the eye) and the cornea (transparent front part of the eye) is closed by new blood vessels growing in the eye, hence, the name 'neovascular'. New blood vessels can cause scarring and narrowing, which can eventually lead to complete closure of the angle. This results in increased eye pressure since the fluid in the eye cannot drain properly. In NVG, the eye is often red and painful, and the vision is abnormal. High pressure in the eye can lead to blindness.

Anti-VEGF medication is a type of medicine that blocks VEGF, therefore, slowing the growth of blood vessels. It is administered by injection into the eye. It can be used early stage, when conventional treatment may not be possible. Most studies report short-term (generally four to six weeks) benefits of anti-VEGF medication, but long-term benefits are not clear.

What were the main results of this review?
We included four studies enrolling a total of 263 participants with NVG. In one study, results beyond the treatment period of 1 week could not be evaluated. In another study, results were uncertain due to the limitation of study design.

The last two studies reported different results for lowering eye pressure; one study showed inconclusive results, and the other study showed that anti-VEGF medications were more effective. The certainty of the evidence in these studies was low, due to limitations in the study designs and inconsistency of results. Therefore, available evidence is insufficient to recommend the routine use of anti-VEGF medication in individuals with NVG.

How up to date is the review?
We searched for studies that were published up to 22 March 2019.

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.

Read the full 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 strategy: 

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.

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