From meta-analysis to Mendelian randomization: Unidirectional perspectives on the association of glaucoma with depression and anxiety

Background: Glaucoma, a primary cause of blindness worldwide, has its association with depression and anxiety noted, yet the understanding of such association is still rudimentary. This study aims to provide the unidirectional perspectives on the association of glaucoma with depression and anxiety, informing public health strategies. Methods: The Meta-analysis screened observational studies from Medline, Embase, and Web of Science, using the modified Newcastle-Ottawa Scale for quality assessment. It employed R’s ’meta’ package to assess the association between glaucoma and depression or anxiety prevalence. The Mendelian Randomization (MR) analysis was conducted using R’s ’TwoSampleMR’ package, based on data from the IEU database data to explore the impact of glaucoma on depression and anxiety. Results: This Meta-analysis included 23 out of 379 studies involving 11,845 glaucoma patients. The combined prevalence of depression among glaucoma patients, derived from 18 cross-sectional studies, stood at 19.42%. Five case-control studies indicated that glaucoma patients had a 6.17-fold higher risk of depression compared to controls. Derived from 16 cross-sectional studies, the consolidated prevalence for anxiety was 19.07%. According to five case-control studies, glaucoma patients exhibited a 4.45-fold increased risk of anxiety compared to controls. MR analysis failed to uncover a causal effect of glaucoma on depression and anxiety. Conclusion: This study suggests that glaucoma patients may experience higher prevalence of depression and anxiety than the general population, with no clear genetic links found. It suggests that environmental factors and non-genetic biological pathways, among others, may play significant roles in their association, though the role of genetic factors cannot be ruled out. These findings highlight the necessity of a comprehensive approach to study the complex factors influencing the association of glaucoma with depression or anxiety and underscore the importance of integrating mental health considerations into glaucoma management to improve medication adherence and disease progression.