PROJECT SUMMARY One in three Americans will develop herpes zoster (HZ, or shingles) in their lifetime, with 10-20% of these cases involving the ophthalmic division of the fifth cranial nerve.1–3 This disease, known as herpes zoster ophthalmicus (HZO), is associated with significant morbidity. Patients with HZO may experience recurrent or chronic inflammation requiring long-term therapy, and sequelae such as permanent vision loss, cataract, glaucoma, and postherpetic neuralgia.1,4–7 A key public health intervention in the prevention of HZ and HZO is vaccination. In 2017, the FDA approved the recombinant zoster vaccine (RZV), Shingrix © (GlaxoSmithKline), a two-dose subunit vaccine for adults ≥ 50 years of age.8 The vaccine has shown efficacy in preventing HZ and HZO, however, several clinical questions remain regarding its use in the prevention of HZO. There is a lack of information on the benefits and risks of RZV in patients with a prior history of HZO, and whether RZV has an impact on severity of HZO. We aim to determine the impact of RZV in patients with a prior history of HZO, and the effect of RZV on HZO severity, disease course, and related health-care utilization. We propose to use big data sources to address clinically relevant questions about HZO and the impact of RZV. To determine the benefits and risks of RZV in patients with a history of HZO, we will use a nonparametric Wilcoxon rank sum test to compare medication usage, a proxy for ocular inflammation, in a vaccinated and non-vaccinated cohort using the OptumLabs health insurance database (Aim 1). To determine the effect of RZV on the severity and chronicity of HZO, we will analyze multiple outcomes of interest, including HZO duration, glaucoma, and vision loss, in the Kaiser Permanente Hawaii electronic medical record system (Aim 2). To compare the ocular morbidity related to HZO in a vaccinated and non-vaccinated cohort, we will be assessing clinic visits and ocular procedures following diagnosis in the OptumLabs health insurance database (Aim 3). By using large, diverse data sources, we aim to obtain generalizable results. Our proposed study will provide clinically relevant information from real-world populations to characterize the impact of RZV on the development and course of HZO. These results can have significant public health implications and be used to formulate recommendations on the use of the vaccine from an ophthalmic perspective.