AimTo evaluate the association of dry eye disease (DED) with depression and anxiety.Patients and methodsWe conducted a systematic review and meta-analysis of studies that reported the prevalence, incidence and/or severity grading of depression and/or anxiety in DED patients and healthy controls. We searched MEDLINE, EMBASE, PsycINFO, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform for relevant studies.ResultsTwenty-two eligible studies consisted of 2 980 026 patients were analyzed. DED was associated with an increased prevalence of depression (summary odds ratio (OR)=2.92, 95% CI: 2.13-4.01, P<0.00001) and anxiety (OR=2.80, 95% CI: 2.61-3.02, P<0.00001). The depression score (standardized mean difference (SMD)=0.81, 95% CI: 0.48-1.15, P<0.00001) and anxiety score (SMD=0.37, 95% CI: 0.10-0.64, P=0.007) were higher in DED patients than in controls. Subgroup analyses revealed that the prevalence and severity of depression are greatest in primary Sjogren's syndrome patients. No study reported the incidence.ConclusionDepression and anxiety are more prevalent in DED patients than in controls. Among patients with DED, those suffering from primary Sjogren's syndrome have higher prevalence and severity of depression.