Methodological quality of the review: High confidence

Author: He M, Wang W, Zhang and Huang W

Geographical coverage: India, Egypt, United Kingdon (UK), Italy, Iran and Germany

Sector: Glaucoma

Sub-sector: Trabeculectomy

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Trabeculectomy (Trab) is the most common surgical treatment for glaucoma. The most common reason for its failure is scar formation during wound healing, which causes fibrosis and the obstruction of aqueous outflow. The ologen implant is one of many attempted solutions for this problem.

Objectives: To evaluate the application of the ologen implant compared to mitomycin C (MMC) on the outcome of trabeculectomy and to examine the balance of risks and benefits.

Main findings: Overall, authors found that the ologen implant is comparable with MMC for Trab in intra-ocular pressure (IOP)-lowering efficacy, reduction in the number of glaucoma medications, success rates and tolerability.

In the meta-analysis, seven randomised controlled trials (RCTs) including 227 eyes were included. Two of the seven studies were conducted in India, and one each was conducted in Iran, Germany, Egypt, UK and Italy.

The weighted mean differences (WMDs) of the intra-ocular pressure reduction (IOPR) comparing the ologen group with the MMC group were 22.98 (95% Cl: 25.07 to 20.89) at one month, 21.41 (23.72 to 0.91) at three months, 21.69 (23.68 to 0.30) at six months, 21.94 (23.88 to 0.01) at 12 months, and 0.65 (22.17 to 0.47) at 24 months. There was no statistical significance except at one and 12 months after surgery.

No significant difference in the reduction in glaucoma medications or complete and qualified success rates were found. The rates of adverse events also did not differ significantly between ologen and MMC. Overall, authors conclude that the ologen implant is comparable with MMC for Trab in IOP-lowering efficacy, reduction in the number of glaucoma medications, success rates and tolerability. Authors also noted that further large-scale, well-designed randomised controlled trials (RCTs) are urgently needed.

Methodology: PUBMED, EMBASE, the Cochrane Library and the Chinese Biomedicine Database were systematically searched for relevant articles. Authors also conducted manual searches of the reference lists of original reports and review articles, and conducted extensive Internet searches on websites and Google Scholar. The titles and abstracts of the remaining studies were independently scanned by two reviewers.

Inclusion criteria consisted of:

(a) RCTs

(b) Population – adult patients (18 years) with uncontrolled glaucoma undergoing trabeculectomy

(c) Intervention – Ologen was compared with intra-operative MMC of any concentration and dose

(d) Outcome variables – at least one of the following outcome variables: IOPR, reduction in glaucoma medications, complete and qualified success rates, or incidence of adverse events

(e) A follow-up time of at least six months

Data extraction and quality assessment of included studies were independently conducted by two reviewers. The methodological quality of each study was assessed using the risk-of-bias tool outlined in the Cochrane Handbook for Systematic Reviews of Interventions.

The efficacy measures were the WMDs for the IOPR, the reduction in glaucoma medications and the relative risks (RRs) for success rates. The tolerability measures were RRs for adverse events.

Authors conducted a meta-analysis assuming the presence of heterogeneity using a random-effects model to combine the data. Statistical heterogeneity was analysed using a chi-square test. The I² statistic was calculated to assess heterogeneity between studies (P<0.10 was considered representative of significant statistical heterogeneity).

Applicability/external validity: This was not discussed fully in this review. However, authors discussed the validity of standardisation of assessment of criteria of success.

Geographic focus: This review focuses on all countries and there are studies from low/middle-income settings.

Publication source: He M, Wang W, Zhang X, Huang W. Ologen implant versus mitomycin C for trabeculectomy: a systematic review and meta-analysis. PLoS One. 2014; 9(1): e85782.

Summary of quality assessment: Overall, there is high confidence in the conclusions about the effects of this study. Methods used to screen studies for eligibility, extract data and quality-assess included studies were appropriately conducted, minimising the risk of bias. In addition, authors appropriately pooled data, taking into account heterogeneity.