Does Lithium Lower the Risk of Glaucoma-A Danish Nationwide Study.

Background: Glaucoma is an optic neuropathy caused by neurodegenerative loss of retinal ganglion cells (RGC). Mechanisms that contribute to RGC death include some of the same mechanisms involved in bipolar disorders (BD) and are the same mechanisms which are targeted by lithium (Li). We conducted a pharmacoepidemiological, population study in Denmark testing the links between Li prescriptions and risk of glaucoma.

Study design: A nationwide, register-based historical, prospective cohort study of participants who were alive and over the age of 18 between January 1, 1996 and December 31, 2019. Participants were followed from the start of study until censoring or glaucoma.

Study results: A total of 7,683,398 individuals (51.3% females) contributing 121,366,461 person-years were included in the study. In the general population, Li exposure was associated with developing glaucoma (HR = 1.10, 95% CI = 1.02-1.19, p = 0.01), but this association was not present in the population with BD (HR = 1.07, 95% CI = 0.93-1.22, p = 0.34). In the cumulative dosage analyses of the entire population, people with no Li prescription (HR = 0.78 95% CI = 0.66-0.93, p = 0.01) and between 365 defined daily doses (DDDs) and 5 × 365 DDDs of Li showed significantly reduced risk of glaucoma, relative to at least one prescription (HR = 0.79, 95% CI = 0.64-0.99, p < 0.05).

Conclusion: BDs as indexed by Li prescription are associated with a greater risk of glaucoma. This is in keeping with generally increased rates of medical comorbidities in BD. While there was no clear dose-response relationship, some of the higher cumulative exposures to Li might be protective relative to a single prescription.