What is the aim of this review?
The aim of this Cochrane review was to compare the effects on intraocular pressure (IOP) between participants who received mitomycin C (MMC) during aqueous shunt surgery and participants who did not receive mitomycin C (MMC) during aqueous shunt surgery.
We do not know whether MMC helps to lower IOP after aqueous shunt surgery for glaucoma. All the relevant trials that we found were small and they reported little information on how they were conducted. The difference in IOP between the MMC and no MMC group 12 months after surgery was too uncertain to say whether MMC helped to lower IOP.
What was studied in this review?
Glaucoma is a progressive disease in which the optic nerve is damaged. Damage to the optic nerve results in visual impairment and may result in blindness when not properly treated. Increased pressure within the eye, known as intraocular pressure or IOP, is the only known risk factor for glaucoma that can be treated. It is thought that by lowering IOP, damage to the optic nerve will be reduced in eyes with glaucoma. Treatments to reduce IOP include eye drops, laser surgery (trabeculoplasty), trabeculectomy (surgical removal of part of the trabecular meshwork), and aqueous shunt surgery (a small device is implanted in the eye to help drain fluid to reduce pressure). Aqueous shunt surgery usually is performed in eyes for which eye drops and laser surgery have not reduced IOP.
Sometimes medications, such as MMC, are used alongside aqueous shunt surgery. These types of medications, known as antifibrotic agents, are used to prevent tissue growth around the implanted device which may block the fluid from draining from the eye. However, it is unknown whether these types of medications are effective and whether there are any unwanted adverse effects. The purpose of this review was to evaluate the effectiveness and safety of MMC when used during aqueous shunt surgery.
What are the main results of the review?
We included five studies with a total of 333 eyes with glaucoma. All five trials reported few details about how they were designed and carried out and few outcomes regarding IOP. Thus, we do not know whether MMC was advantageous compared with placebo. We found no clear benefit or harm for MMC versus no MMC during aqueous shunt surgery.
How up-to-date is this review?
Cochrane researchers searched for studies that had been published up to 13 February 2018.
We found insufficient evidence in this review to suggest MMC provides any postoperative benefit for glaucoma patients who undergo aqueous shunt surgery. Data across all five included trials were sparse and the reporting of study methods required to assess bias was inadequate. Future RCTs of this intervention should report methods in sufficient detail to permit assessment of potential bias and estimate target sample sizes based on clinically meaningful effect sizes.
Glaucoma affects more than 70 million people worldwide, with about 10% being bilaterally blind, making it the leading cause of irreversible blindness globally. In patients with advanced glaucoma or those who have failed medical treatment without achieving adequate intraocular pressure (IOP) control, trabeculectomy (glaucoma filtration surgery where an ostium is created into the anterior chamber from underneath a partial thickness scleral flap to allow for aqueous flow out of the anterior chamber intointo the subconjunctival space forming a filtering bleb) and aqueous shunt surgery for more complex and refractory cases remain the mainstay therapies. Proliferation of fibrous tissue around an implanted aqueous shunt may block the diffusion of aqueous humour. Mitomycin C (MMC) is one of two commonly used adjunct antifibrotic agents used during aqueous shunt surgery to prevent proliferation of fibrous tissue. However, the effectiveness and safety of the use of intraoperative MMC during aqueous shunt surgery has not been established.
To evaluate the effectiveness and safety of MMC versus no MMC used during aqueous shunt surgery for reducing IOP in primary and secondary glaucoma.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 13 February 2018.
We included randomized controlled trials (RCTs) in which one group of participants received MMC during aqueous shunt surgery and another group did not. We did not exclude studies based on outcomes.
Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text reports of potentially relevant studies and assessed them for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We used standard methodological procedures expected by Cochrane.
We included five RCTs, with a total of 333 eyes with glaucoma randomized, and identified two ongoing trials. All included trials examined the effect of MMC versus no MMC when used during aqueous shunt surgery for glaucoma. The trials included participants with different types of uncontrolled glaucoma. One study was conducted in China, one in Saudi Arabia, two in the USA, and one study was a multicenter study conducted in Brazil, Canada, Scotland, and USA. We assessed all trials as having overall unclear risk of bias due to incomplete reporting of study methods and outcomes; two of the five trials were reported only as conference abstracts.
None of the included trials reported mean decrease from baseline in IOP; however, all five trials reported mean IOP at 12 months post-surgery. At 12 months, the effect of MMC on mean IOP compared with no MMC was unclear based on a meta-analysis of trials (mean difference -0.12 mmHg, 95% CI -2.16 to 2.41; low-certainty evidence). Two trial did not report sufficient information to include in meta-analysis, but reported that mean IOP was lower in the MMC group compared with the no MMC group at 12 months.
None of the included trials reported mean change from baseline in visual acuity; however, one trial reported lower mean LogMAR values (better vision) in the MMC group than in the no MMC group at 12 months post-surgery. None of the included studies reported the proportion of participants with stable best-corrected visual acuity. Three trials reported that loss of vision was not significantly different between groups (no data available for meta-analysis).
None of the included studies reported the proportion of participants with a postoperative hypertensive phase, which is defined as IOP > 21 mmHg within 3 months after surgery. Two trials reported adverse events (choroidal effusion, corneal edema, flat anterior chamber, and retinal detachment); however, due to small numbers of events and sample sizes, no clear difference between MMC and placebo groups was observed.