Herpes zoster vaccination and the risk reduction of ophthalmic diseases: A nationwide emulated target trial in South Korea

Recent evidence has suggested that administration of the live attenuated zoster vaccine may be associated with a reduced risk of developing conditions such as dementia and cardiovascular diseases, potentially through the prevention of herpes zoster infection. This study aims to evaluate whether herpes zoster vaccination can reduce the risk of ophthalmic diseases, including glaucoma and cataract. This target trial emulation study in South Korea included 2,519,582 individuals aged ≥50 years. The cohort was established by integrating health insurance data from the Korea Health Insurance Review and Assessment Service, national health examination data from the Korean National Health Insurance Service, and vaccination data from the Korea Disease Control and Prevention Agency. Exposure was defined as receipt of at least one dose of live zoster vaccination between January 1, 2012, and December 31, 2021. The primary outcomes included ophthalmic events and follow-up extended from the index date to January 31, 2024. A propensity score-matched analysis was conducted, and Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). After 1:1 propensity score matching, 570,334 individuals were included in both the vaccinated and unvaccinated groups (mean age, 61.07 years [SD, 3.48]; 54.34% females). Vaccination against herpes zoster was associated with an 18% lower risk of developing any ophthalmic disease (0.82 [95% CI, 0.81-0.82]), with the strongest associations observed for glaucoma (0.81 [95% CI, 0.80-0.82]) and cataract (0.82 [95% CI, 0.82-0.83]). The protective effect was more pronounced among male and individuals aged <60 years. This association was sustained for up to eight years, with the greatest benefit observed between one and four years following vaccination. Live attenuated zoster vaccination significantly reduced the incidence of ophthalmic diseases, particularly glaucoma and cataract, indicating protective effects beyond prevention of shingles.