Methodological quality of the review: High confidence

Author: Green E, Wilkins M, Bunce C, Wormald R

Geographical coverage: USA and Israel

Sector: Glaucoma

Sub-sector: Glaucoma surgery

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: A surgical treatment of glaucoma (trabeculectomy or Trab) involves creating a channel through the sclera in an attempt to lower the intra-ocular pressure (IOP). This treatment may fail due to scar tissue blocking the exit of the surgically created channel. To inhibit wound healing and prevent the conjunctiva scarring down onto the sclera, anti-metabolites such as 5-Fluorouracil (5-FU) are used. It is important to assess and update the effectiveness of this approach.

Objectives: To assess the effects of both intra-operative application and post-operative injections of 5-FU in the eyes of people undergoing surgery for glaucoma at one year.

Main findings: In this review, 12 trials and 1319 participants were included. In general, the methodological quality of the trials was not high with a high risk of detection bias. Surgical failure was significantly reduced in the first year after Trab in eyes at high risk of failure and those undergoing surgery for the first time receiving regular-dose 5-FU post-operative injections (RR 0.44, 95% confidence interval (CI) 0.29 to 0.68 and 0.21, 0.06 to 0.68, respectively). There were no surgical failures in studies assessing combined surgery.

There was no difference in the low-dose post-operative 5-FU injection group in patients undergoing primary Trab (RR 0.93, 95% CI 0.70 to 1.24). It was found that pre-operative 5-FU in patients undergoing primary Trab significantly reduced the risk of failure (RR 0.67, 95% CI 0.51 to 0.88). IOP was also reduced in the primary Trab group receiving intra-operative 5-FU (mean difference (MD) -1.04, 95% CI -1.65 to -0.43) and regular-dose post-operative 5-FU (MD -4.67, 95% CI -6.60 to -2.73).

No significant change occurred in the primary Trab group receiving low-dose post-operative 5-FU (MD -0.50, 95% CI -2.96 to 1.96). IOP was particularly reduced in the high risk of failure population receiving regular-dose post-operative 5-FU (MD -16.30, 95% CI -18.63 to -13.97). No difference was detected in the combined surgery population receiving regular-dose post-operative 5-FU (MD -1.02, 95% CI -2.40 to 0.37).

There was no evidence of an increased risk of serious sight-threatening complications after 5-FU injections. The quality of evidence varied between sub-groups and outcomes. The evidence for combined surgery and low-dose post-operative 5-FU was found to be very low. This may be attributed to small sample size.

The authors conclude that, currently, post-operative injections of 5-FU are rarely used as part of routine packages of post-operative care but are increasingly used on an ad hoc basis. This presumably reflects an aspect of the treatment that is unacceptable to both patients and doctors. None of the trials reported on the participants’ perspective of care, which constitutes a serious omission for an invasive treatment such as this.

Methodology: The following databases were searched for relevant studies: the Cochrane Eyes and Vision Group Trials Register (CENTRAL), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, EMBASE, the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic searches for trials. In addition, the reference lists of relevant articles and the Science Citation Index were searched and investigators and experts were also contacted for details of additional relevant trials.

Randomised trials of intra-operative application and post-operative 5-FU injections compared with placebo or no treatment in Trab for glaucoma were included in this review.

Trial quality and data extraction were done by two reviewers independently. Standard methodological procedures accepted by the Cochrane Collaboration were used. Trial investigators were contacted for missing information. Data was summarised using risk ratio (RR), Peto odds ratio and mean difference, as appropriate

Applicability/external validity: Authors did not discuss the applicability/external validity of the results.

Geographic focus: The authors did not specify the focus of the review geographically.

Summary of quality assessment: This review was based on comprehensive searches of the literature. Methods used to screen studies for inclusion and extract data were appropriately conducted, thus minimising bias. Overall, there is high confidence in the conclusions about the effects of this study as minor limitations were identified.