Effectiveness of multiple therapeutic strategies in neovascular glaucoma patients: A PRISMA-compliant network meta-analysis

Methodological quality of the review: Low Confidence

Authors: Dong Z, Gong J, Liao R, Xu S

Region: China, Egypt

Sector: Glaucoma

Sub-sector: Neovascular Glaucoma

Equity focus:  None specified

Review type: Other review

Quantitative synthesis method, if applicable: meta-analysis

Qualitative synthesis method, if applicable: Not applicable

Background:

Neovascular glaucoma (NVG) is a severe form of secondary glaucoma, which usually occurs secondary to central retinal vein (artery) occlusion, diabetic retinopathy, and retinal periphlebitis. Neovascularization can cause extensive anterior synechia and can destroy the normal anatomical structure, thereby increasing surgical difficulty. Presently, NVG therapeutic strategies are diverse, but the therapeutic effects are still not ideal, and the application of a general antiglaucoma drug is inappropriate for this disease.

Objectives:

The authors performed a network analysis to assess the effect of multiple therapeutic strategies on the treatment of NVG patients. Comprehensively analysing different therapeutic strategies for NVG by network meta-analysis to determine the best strategy through direct and indirect comparisons.

Main findings:

The authors included 27 articles assessing a total of 1,884 NVG patients in their analysis.

The types of surgical treatments included cyclocryotherapy, cyclophotocoagulation, glaucoma valve implantation, retinal photocoagulation, retinal cryotherapy, iris photocoagulation, trabeculectomy, and vitrectomy.

The types of agents used included bevacizumab, 5-fluorouracil, interferon, mitomycin, and ranibizumab. Antibiotics and steroids, such as tobramycin and dexamethasone, were generally used after surgery.

Using the network analysis, interferon and mitomycin plus trabeculectomy (94.9%), glaucoma valve implantation (86.9%), and iris photocoagulation plus trabeculectomy (81.9%) were found to be the most likely to improve treatment success rate in NVG patients based on an inconsistency model.

In conclusion, a regimen including mitomycin, interferon, and trabeculectomy was the most likely to improve the treatment success rate in NVG patients. The application of a glaucoma valve and bevacizumab were most beneficial for improving patient treatment success rate in terms of surgery and agent, respectively.

The authors identified several limitations in their study. First, the results of the network meta-analysis contained global and local inconsistencies that might have affected accuracy. Second, in the results of the traditional meta-analysis, large standard errors rendered the results imprecise and poorly robust. Third, we did not perform the Grading of Recommendations Assessment and Development and Evaluation analysis because the included studies did not include design blindness.

Methodology:

This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA). For this network analysis, the authors searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Chinese databases, including the China National Knowledge Infrastructure, the China Science Periodical Database (the Wanfang Database), the VIP journal integration platform, and China Biology Medicine database RCTs, published from the date of database inception to April 2017. They used the following keywords: neovascular glaucoma, iris neovascularization, haemorrhagic glaucoma, and random∗.

Inclusion criteria included: prospective randomized control trial (RCT) design; patients with a clinical diagnosis of NVG; controlled study of different therapeutic strategies related to different surgeries and/or drugs; outcome assessments that included treatment success rate based on the number of patients who achieve normal IOP during the follow-up period.

Two authors independently extracted data of included studies. They assessed the methodological quality of the included trials using the Cochrane Collaboration tool. Studies were graded as having a “low risk,” “unclear risk,” or “high risk” of bias across the seven specified domains.

The authors conducted a random-effects network meta-analysis, which used a frequentist framework.

Applicability/external validity:

The effects of interferon and mitomycin plus trabeculectomy and iris photocoagulation plus trabeculectomy are robust, and glaucoma valve implantation plus mitomycin and glaucoma valve implantation remain controversial. Thus, further studies are still needed, particularly well-designed RCTs. Moreover, detailed descriptions of NVG stage and standardized surgical process are necessary to further reduce differences among studies. In these three included studies, the regimen achieved an approximately 96% treatment success rate, and the mean IOP measured during follow-up ranged from 16.32 to 17.1mm Hg. Therefore, this strategy is worth testing in the future with well-designed RCTs.

Geographic focus:

The authors did not provide applicability of findings to low- and middle-income settings.

Summary of quality assessment:

This systematic review does not provide information on several areas key to attributing a higher confidence rating. These include: no full text independent screening, search restricted to published articles, studies not separated by risk, and insufficient discussion of heterogeneity. For these reasons it has been awarded Low Confidence.