Abstract
Purpose :
Many international studies have reported associations between herpes zoster ophthalmicus (HZO) and stroke, with some theories which postulate that intracranial branches of the ophthalmic nerve may be implicated. We sought to test this association and further characterize HZO and stroke risk using a U.S. administrative medical claims database.
Methods :
A retrospective, matched case-control study was performed using a national database queried from 1/1/2002-6/30/2021. Cases of HZO were identified using ICD 9/10 codes. The index date for cases was considered the earliest date of diagnosis of HZO. Controls were matched up to 3:1 for age, gender, race, and insurance eligibility date (+- 4 months). Exclusion occurred for being < 55 years old, having prior or concurrent herpes simplex infection, and having <2 years in the insurance plan or previous stroke prior to the index date. The primary outcome was defined as having a diagnosis of any new ischemic, hemorrhagic, or non-specific cerebrovascular accident after the HZO index date. Multivariate Cox proportional-hazards models were constructed with inverse proportional treatment weighting. A second analysis used a self-controlled case series (SCCS) design of HZO cases to assess various times frames for their risk of stroke before and after the onset of HZO.
Results :
25,720 cases and 75,924 controls met our eligibility criteria. 1,712 (6.7%) and 4,544 (6.0%) strokes occurred in the case and control groups respectively, conferring an 18% increased risk of stroke in the observed 2-year post-HZO period (HR=1.18, 95% CI: 1.12-1.25, p<0.001). (See Figure 1 for the KM curve.) Sensitivity analyses that varied date of censoring and definition of stroke (excluded TIA) showed similar results. SCCS analysis showed the risk for stroke was highest in the month immediately after HZO episode compared to any other time range (1-30 days after, relative risk 1.58, p < 0.001) and even higher when assessing time more distal time points prior to the HZO diagnosis (days 1-30 after HZO diagnosis had RR=1.69 (95% CI: 1.38-2.07) and RR=1.93 (95% CI: 1.55-2.39) compared with days -120 to -91 and -150 to -121 prior to index, respectively (p<0.001).
Conclusions :
After accounting for stroke risk factors, our analysis confirms the association between HZO and stroke, with highest risk in the immediate month after an episode.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.