This study was registered on INPLASY202040120. It has been reported according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocol .
Study selection criteria
Type of studies
Only randomized controlled trials (RCTs) will be included in this study, which explored the efficacy and safety of DTFC for the treatment of POAG. We will exclude any other studies, such as animal study, review, case report, uncontrolled trial, non-RCTs and quasi-RCTs.
Type of participants
Any patients who were diagnosed as POAG in spite of country, race, gender, age, and severity of POAG will be included.
Type of interventions
In the experimental group, all patients who received DTFC as their solely treatment will be included.
In the control group, subjects could receive any treatments without restrictions. However, we will not consider study which involved any forms of DTFC as its comparator.
Types of outcomes
Mean intraocular pressure; and
Best corrected visual acuity.
Bioelectric activity of the retina;
Rate of progression of glaucoma;
Quality of life (as assessed by 36-Item Short Form Survey); and
Data sources and search strategy
A comprehensive search will be performed from origin to the March 1, 2020 in the electronic databases of Cochrane Library, MEDLINE, EMBASE, CINAHI, ACMD, China National Knowledge Infrastructure, and Wanfang Data. We will not apply limitations related to the language and publication status. We will only consider RCTs that appraised the efficacy and safety of DTFC for the treatment of POAG. We have summarized search strategy sample for Cochrane Library (table 1), and will create similar search strategies for other electronic databases. In addition, we will also scrutinize other sources, such as Google Scholar, conference proceedings, and reference lists of included trials.
Two researchers will independently identify titles/abstracts of sought citations to remove unrelated studies. Then, full papers of potential trials will be further inspected against all eligibility criteria. If any differences are identified, we will invite a third researcher to solve them by discussion. All reasons for excluded studies will be listed. We will exert the process of study selection in a flowchart.
Data extraction and management
Two researchers will independently extract data from all included RCTs using a predefined standard data extraction form. Any divergences between two of them will be resolved through discussion with a third researcher. The extracted information consists of study information (e.g. title, first author), patient characteristics (e.g. diagnosis criteria, eligibility criteria), study methods (e.g. sample size, randomization); details of intervention and controls (e.g. treatment types, dosage), outcome measurements, adverse events, and conflict of interest.
Dealing with missing data
We will contact primary authors to request any unclear or missing data. If it can not be obtained, we will analyze available data using intention-to-treat analysis.
Risk of bias assessment
Two researchers will independently appraise methodological quality for all eligible RCTs using Cochrane Handbook for Systematic Reviews of Interventions Tool . Any disagreements will be resolved by a third researcher by consultation and a consensus will be reached.
Quality of evidence rating
Two researchers will independently assess the overall strength of the evidence using Grading of Recommendations Assessment, Development and Evaluation tool . Its results will be demonstrated in the table of Summary of Findings. A third researcher will help to solve any disagreements.
RevMan 5.3 software (Cochrane, London, UK) will be utilized to perform statistical analysis. We will estimate continuous outcome values using mean difference or standardized mean difference with 95% confidence intervals (CIs), and dichotomous outcome values using risk ratio with 95% CIs. We will examine heterogeneity using I² statistic. We will use a fixed-effect model to pool the data (I² ≤50%), and will utilize a random-effect model (I² >50%) to synthesize the data. If I² ≤50% and sufficient number of eligible study is included, we will carry out meta-analysis. Otherwise, if I² >50%, we will conduct a subgroup analysis to investigate the sources of heterogeneity.
A subgroup analysis will be carried out according to the variations in study and patient characteristics, different types of interventions and controls, and different study quality.
A sensitivity analysis will be conducted to test the stability of conclusions by eliminating low quality trials.
If necessary, we will perform a funnel plot and Egger’s regression test to check reporting bias when over 10 RCTs are included.
This study will be published in print, conferences or by peer-reviewed journals.
Any changes to this protocol will be noted with reference to saved searches and analysis.