Key messages

• Mitomycin C might be more effective in reducing intraocular pressure and increasing qualified success rate compared to 5-fluorouracil.
• Mitomycin C might be associated with a higher incidence of complications than 5-fluorouracil (bleb leak, late hypotonia, narrow anterior chamber, endophthalmitis, cataract development).

What is the evidence.
See evidence matrix  in Epistemonikos later

We found four systematic reviews [1],[2],[3],[4] that included  17 primary studies reported in 19 references [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],
[17],[18],[19],[20],[21],[22],[23], of which, 12 correspond to randomized controlled trials, reported in 14 references [6],[8],[9],[10],[12],[13],[14],[15],
[16],[17],[19],[21],[22],[23]. One of the trials [16], was conducted in patients with neovascular glaucoma, whose surgery of choice is not trabeculectomy, so it was excluded in the analysis of this article.

This table and the summary in general are based on 11 randomized trials, since the observational studies did not increase the certainty of the evidence or provide additional relevant information.

What types of patients were included*

Regarding the type of glaucoma, five trials included patients with more than one type of glaucoma [6],[8],[15],[21],[22], four trials included patients with open-angle glaucoma [10],[13],[19],[23]. In two trials, the type of glaucoma was not reported [9],[12].

Regarding the risk of trabeculectomy failure, four trials included patients considered to be as high risk [6],[8],[9],[13], five included patient with a low risk of failure [10],[15], [19],[21],[23] and one trial included both high and low risk patients [22]. In one trial, the risk of trabeculectomy failure was not reported [12].

What types of interventions were included*

All trials compared mitomycin C against 5-fluorouracil [6],[8],[9],[10],[12],[13],[15],[19],[21],[22],[23].

The use of mitomycin was during the intraoperative period in all of the trials [6],[8],[9],[10],[12],[13],
[15],[19],[21],[22],[23]. The dose used was a 0.2 mg/ml solution for 2 minutes in three trials [12],[19],[21], a 0.2 mg/ml solution for 5 minutes in two trials [22],[23], a 0.4 mg/ml solution for 2 minutes in one trial [15], a 0.4 mg/ml solution for 2.5 minutes in one trial [9], a 0.4 mg/ml solution for 5 minutes in one trial [8], a 0.5 mg/ml solution for 3.5 minutes in one trial [13], a 0.5 mg/ml solution for 5 minutes in one trial [6] and a dose of 0.02 mg in one trial [10].

The use of 5-fluorouracil was during the intraoperative period in six trials [10],[12],[13],[15],[19],[21], of which in five a solution of 50 mg/ml was administered for 5 minutes [12],[13],[15],[19],[21] and a dose of 5 mg was administered in one trial [10]. In the remaining five trials, 5-fluorouracil was used postoperatively [6],[8],[9],[22],[23]; in three trials  10 doses of 5 mg were administered [6],[8],[9], and in two 7 doses of 5 mg were administered [22],[23]. 

What types of outcomes
were measured

The trials measured multiple outcomes, which were grouped by the systematic reviews as follows:

• Failure of trabeculectomy at one year.
• Average intraocular pressure at the end of follow-up or at one year
• Percentage decrease in postoperative intraocular pressure.
• Absolute decrease in postoperative intraocular pressure.
• Qualified success (objective intraocular pressure independent of the use of medical treatment)
• Complete success (objective intraocular pressure without the need of medical treatment).
• Complications (bleb leak, late hypotony, maculopathy, cataract, narrow anterior chamber, choroidal detachment, corneal epitheliopathy, tenon cyst, hyphema y endophthalmitis).
• Number of drugs used during postoperative period.
• Decrease in visual acuity.
• Need for reoperation or post-surgical laser procedure
• Absolute decrease in postoperative intraocular pressure in a low-risk group

To whom this evidence does and does not apply

• The evidence presented in this summary applies to glaucoma patients with surgical treatment indication in patients with and withour high risk of trabeculectomy failure.
• Most patients included in the trials were adults. So, this evidence should not be extrapolated to pediatric patients.

• The outcomes intraocular pressure and qualified succes were chosen because they are crucial for the success of the procedure. In addition, complications of surgery were chosen as safety parameters. This selection is based on the opinion of the authors of the summary, but generally agree with the ouctomes reported in the systematic reviews.

• Mitomycin C could increase qualified success and be more effective in reducing mean intraocular pressure than 5-fluorouracil. However, it might be associated to more complications. Also, it is important to keep in mind the limitations of the existing evidence.

• Only one systematic review [1] looked for economic outcomes. However, no data was found in the trials. So, it is not clear whether the cost/benefit would be favorable for the use of mitomycin C considering the increase in the efficacy of trabeculectomy, but also the increase in the complication rate compared to 5-fluorouracil.

• The evidence presented in this summary would probably lead to variable decisions depending on whether clinicians place more value on efficacy or safety.
• The limited certainty of the existing evidence can also be a factor that leads to variations in decision-making.

Differences between this summary and other sources

• The conclusions of this summary agree with the most complete systematic review identified [1], being cautious about the results due to the limitations of the evidence and the risk of bias of the primary studies.
• The conclusions of this summary coincide with the main guidelines which recommend the use of antimetabolites taking into account their risks and benefits [24],[25].

• The probability that future research changes the conclusions of this summary is high, due to the uncertainty on the existing evidence.
• There are at least two ongoing trials in the International Clinical Trials Registry Platform of the World Health Organization evaluating this question [26],[27]. On the other hand, there are trials comparing the mitomicyn C against new adjuvant agents (e.g. bevacizumab) [28],[29].
• No systematic reviews were found in the International prospective register of systematic reviews (PROSPERO) of the National Institute for Health Research.