Types of studies

We will include randomised controlled trials (RCTs) only. We will include reports of RCTs prepared in any language irrespective of their publication status.

Types of participants

Participants will have OAG of any type, including primary and secondary OAG. Closed angle glaucoma will be excluded. As there are no universally‐accepted criteria by which glaucoma may be defined, we will permit studies to use their own definitions of glaucoma (provided these are clearly stated). In addition, participants with ocular hypertension, normal tension glaucoma, or possible glaucoma (suspects for glaucoma) will be included. We will not apply any restrictions regarding location, setting, or demographic factors.

Types of interventions

The intervention will be ab interno trabecular bypass surgery with Hydrus (Ivantis Inc., Irvine, California).

We will compare ab interno trabecular bypass surgery with Hydrus to:

1. laser treatment (selective laser trabeculoplasty or argon laser trabeculoplasty);

2. other MIGS techniques;

3. conventional glaucoma surgery (trabeculectomy)

4. medical therapy; or

5. in combination with phacoemulsification compared with phacoemulsification alone (since phacoemulsification cataract surgery is known to reduce IOP (Mansberger 2012)).

Types of outcome measures

We will not use the reporting of particular outcomes as a criterion for eligibility for review. We will not exclude studies from review solely on the grounds of an outcome of interest not being reported.

Electronic searches

The Cochrane Eyes and Vision Information Specialist will search the following electronic databases for randomised controlled trials and controlled clinical trials. There will be no language or publication year restrictions.

• Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library (latest issue) (Appendix 1);

• MEDLINE Ovid (1946 to present) (Appendix 2);

• Embase Ovid (1980 to present) (Appendix 3);

• ISRCTN registry (www.isrctn.com/editAdvancedSearch (Appendix 4);

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) (Appendix 5);

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp) (Appendix 6).

Searching other resources

We will search the reference lists of included studies for other possible studies and will contact any individuals or organisations who, we believe, may have conducted or be conducting relevant RCTs. We will also search the website of the manufacturer (Ivantis Inc., Irvine, California; www.ivantisinc.com) for any information on forthcoming trials.

Selection of studies

Two review authors working independently will screen titles and abstracts of all articles identified by the search using web‐based online review management software (Covidence 2015). If abstracts are not available, we will screen full‐text articles. Two review authors will independently assess full‐text reports of all potentially eligible studies. If there is disagreement regarding eligibility, a third review author will arbitrate. If any full‐text reports are rejected, we will record the reasons for this.

Data extraction and management

We will extract data from reports of included studies using a data collection form, which will be developed and piloted on the first five studies included. Two review authors will work independently to extract study characteristics from reports of each study and enter the data into Review Manager 5 (RevMan 5) (Review Manager 5 2014). If there is disagreement, a third independent review author will arbitrate.

We will collect the following information on the characteristics of included studies (Appendix 7):

• Year of publication.

• Year of study.

• Country of study.

• Sample size.

• Participation rate.

• Method of recruitment.

• Eligibility criteria.

• Diagnostic criteria.

• Method of randomisation.

• Method of masking.

• Number of study arms.

• Types of participants.

• Types of interventions.

• Types of comparators.

• Use of phacoemulsification at the same time as the intervention.

We will collect the the following data regarding outcomes (Appendix 7):

• IOP at baseline.

• IOP at follow‐up.

• Number of glaucoma medications at baseline.

• Number of glaucoma medications at follow‐up.

• Intraoperative complications.

• Postoperative complications or secondary surgery.

• Duration of follow‐up.

• Loss to follow‐up.

• Intervals at which outcomes were assessed.

Where data on included studies are missing or unclear, we will contact the individuals or organisations involved to obtain clarification. We will collect and use the most detailed numerical data available to facilitate analyses of included studies. We will attempt to obtain these data from individuals or organisations in preference to less precise methods such as extracting numeric data from graphs. If this is necessary, two independent review authors will extract the data and a third review author will arbitrate, in case of disagreement.

Assessment of risk of bias in included studies

We will use the latest version of the Cochrane 'Risk of bias' tool as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) to assess the risk of bias and assign judgements of this for included studies.

Measures of treatment effect

The primary outcome is the proportion of participants who are drop‐free two years after randomisation. We will use a risk ratio as the treatment effect measure. In assessing this effect measure, we will report how prescribing of IOP‐lowering eye‐drops was determined during follow‐up. We will examine whether the people measuring IOP and those deciding upon the prescribing of IOP‐lowering eye‐drops were masked to treatment group.

We will report mean change in IOP from randomisation to two years after randomisation. Secondary safety outcomes will be reported as risk ratios. Health‐related quality of life outcomes will be reported as differences in means or risk ratios for continuous and binary data, respectively.

Unit of analysis issues

We will assess whether included studies have included one or two eyes from each subject and whether or not randomisation has been conducted at the level of the participant or the eye. There is a potential for medical treatments, such as topical beta blockers used for one eye, to influence the outcome in the other eye (Piltz 2000). Surgery to lower IOP in one eye may also affect the IOP of the fellow eye (Radcliffe 2010). Therefore, we will exclude studies that have adopted a paired design.

Dealing with missing data

We will endeavour to minimize missing outcome data by contacting individuals and organisations to obtain them. If the data are unavailable but the level of missing data in each group and reasons for missing data in each group are similar we may simply analyse available‐case data if an intention‐to‐treat (ITT) analysis has not been performed. We will report if authors have conducted their own ITT analysis despite missing data, but we will document whether they provide any justification for the method they have used to deal with missing data and whether they have compared their ITT result with an available‐case result.

Assessment of heterogeneity

We will assess the heterogeneity between trials by careful examination of the study reports, assessing forest plots and an examination of the I² value. We will consider I² values greater than 50% as indicative of substantial heterogeneity, suggestive that meta analysis might not be wise ‐ however, consideration will be given to the consistency of the effect estimates. If all estimates are in the same direction, we might meta‐analyse even where heterogeneity is evident; we will comment on the heterogeneity.

Assessment of reporting biases

We will use a funnel plot to assess the risk of publication bias if there are more than 10 trials within our review.

Data synthesis

We will undertake a meta‐analysis where data appear clinically, methodologically, and statistically homogeneous. We will check that participants, interventions, comparators, and outcomes are sufficiently similar to give a clinically meaningful result and that our I² result does not indicate considerable inconsistency (i.e. I² less than 50%). If all estimates are in the same direction, we might meta‐analyse even where heterogeneity is evident but will comment on this. We will use a random‐effects model unless there are fewer than three eligible studies, in which case, we will use a fixed‐effect model.

Subgroup analysis and investigation of heterogeneity

We will undertake a subgroup analysis. The effect modifier to be examined will be use of phacoemulsification as a cointervention. Phacoemulsification has been shown to reduce IOP (Mansberger 2012). We will therefore analyse whether the effect of Hydrus surgery differs depending on whether phacoemulsification is used as a cointervention.

Sensitivity analysis

We will assess the impact of including studies at high risk of bias for an outcome in one or more key domains.