Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections

Objective: To assess psychological stress and other factors as possible triggers of ocular herpes simplex virus (HSV) recurrences. Design: A prospective cohort study nested in a randomized, placebo-controlled, clinical trial. Setting: Fifty-eight community-based or university sites. Participants: Immunocompetent adults (N = 308), aged 18 years or older, with a documented history of ocular HSV disease in the prior year and observed for up to 15 months. Exposure Variables: Psychological stress, systemic infection, sunlight exposure, menstrual period, contact lens wear, and eye injury recorded on a weekly log. The exposure period was considered to be the week before symptomatic onset of a recurrence. Main Outcome Measure: The first documented recurrence of ocular HSV disease, with exclusion of cases in which the exposure week log was completed late after the onset of symptoms. Results: Thirty-three participants experienced a study outcome meeting these criteria. Higher levels of psychological stress were not associated with an increased risk of recurrence (rate ratio, 0.58; 95% confidence interval, 0.32-1.05; P=.07). No association was found between any of the other exposure variables and recurrence. When an analysis was performed including only the recurrences (n = 26) for which the exposure week log was completed late and after symptom onset, there was a clear indication of retrospective overreporting of high stress (P= .03) and systemic infection (P=.01). Not excluding these cases could have produced incorrect conclusions due to recall bias. Conclusions: Psychological stress does not appear to be a trigger of recurrences of ocular HSV disease. If not accounted for, recall bias can substantially overestimate the importance of factors that do not have a causal association with HSV infection.