Depression and Depressive Symptoms in Glaucoma: A Systematic Review and Meta-Analysis of Comparative, Prevalence, and Longitudinal Evidence.

BACKGROUND: Evidence suggests that people with glaucoma may experience more depressive symptoms than those without glaucoma, but prior estimates have been limited by heterogeneous ascertainment and insufficient separation of comparative, prevalence, and longitudinal evidence. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, Wanfang, VIP, CNKI, ChiCTR, and ClinicalTrials.gov to March 27, 2026. Eligible studies reported depression outcomes among individuals with glaucoma; studies included in the primary comparative analysis additionally required a non-glaucoma comparison group. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale (NOS) for cohort/case-control studies and Joanna Briggs Institute (JBI) tools for cross-sectional studies. Random-effects meta-analyses used restricted maximum likelihood (REML) as the primary estimator; DerSimonian-Laird models were sensitivity analyses. Certainty of evidence was assessed using the GRADE framework adapted for observational evidence. RESULTS: Forty-nine studies were included qualitatively. Sixteen studies including 14,030 glaucoma participants and 4,472,723 controls contributed to the primary odds ratio meta-analysis. Glaucoma was associated with higher odds of depression (OR, 2.80; 95% CI, 1.66-4.74; I 2 = 95.95%; approximate prediction interval 0.32-24.47). Results remained significant across sensitivity analyses excluding self-reported glaucoma studies, unclear glaucoma ascertainment, and a very large database study. Thirty-eight studies including 21,705 patients with glaucoma contributed to the single-group prevalence meta-analysis; pooled depression prevalence was 26.03% (95% CI, 21.10%-31.64%; prediction interval 5.98%-66.04%). Longitudinal evidence was limited and heterogeneous; one UK Biobank cohort suggested a longitudinal association with incident hospitalized depression among participants with glaucoma (HR, 1.54; 95% CI, 1.01-2.34). GRADE certainty was very low for the comparative, prevalence, and longitudinal evidence domains. CONCLUSIONS: Very low-certainty observational evidence suggests that depression or depressive symptoms are more common among individuals with glaucoma; however, whether glaucoma precedes, contributes to, or results from depressive symptoms remains uncertain. The observed association may reflect complex bidirectional relationships between glaucoma-related visual burden and depressive symptoms. Ophthalmic care should incorporate pragmatic depression awareness and referral pathways, while future longitudinal studies should use standardized glaucoma and depression ascertainment with adequate adjustment for visual, clinical, and socioeconomic confounders.