Abstract: We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.

Plain-language summary: This review included 43 randomized controlled trials (3497 people with dry eye) that compared OTC artificial tears with other OTC artificial tears, with no treatment, or with placebo. We considered participant symptoms to be the primary outcome for this review. We recorded other commonly performed dry eye tests as secondary outcomes (e.g. vision, tear stability). We measured primary and secondary outcomes at two and four weeks, although we also considered other time points in this review. We searched for trials up to December 2015. This review analyzed many OTC artificial tear formulations, and most of the literature indicates uncertainty as to which OTC artificial tear works best. The literature also shows that OTC artificial tears may be effective at treating dry eye symptoms and that OTC artificial tears are generally safe, although not without side effects. We also identified an additional 18 potentially eligible trials that were registered, but did not provide any results or publications. These trials may have enrolled 2079 total participants for whom no data are available. Without the results of these trials, the effects of the OTC artificial tears that they evaluated are unknown. The overall quality of the evidence was low for the various OTC artificial tear formulations compared in this review. This finding indicates that future published research may have an important impact on the conclusions currently provided in this review.