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