Psychological Stress and Other Potential Triggers for Recurrences of Herpes Simplex Virus Eye Infections

Document Type


Publication Date



Eye Infections, Herpes Simplex Virus, Simplexvirus, Stress

Digital Object Identifier (DOI)



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.

HERPES SIMPLEX virus (HSV) is a leading cause of eye infections and visual loss. An important contributor to visual loss from HSV infection is its recurring nature. Several factors have been suggested as potential triggers of recurrent ocular, orofacial, or genital HSV disease, including upper respiratory tract infection, fever, sunlight, seasonal conditions, emotional factors, psychological stress, trauma, and menstruation. However, results from these studies have been inconsistent, and only a few studies have assessed ocular HSV recurrences.

In a randomized, placebo-controlled, clinical trial, we found that 12 months of oral acyclovir therapy was beneficial in reducing the incidence of ocular HSV recurrences in participants with a recent history of active ocular HSV disease. In both treatment groups, the number of prior episodes of HSV eye disease was the only baseline or historical factor that was a strong predictor of a recurrence. Herein, we report the results of a prospective cohort study, nested within this clinical trial, that assessed psychological stress and other factors as possible triggers of recurrent HSV eye disease.

Was this content written or created while at USF?


Citation / Publisher Attribution

Archives of Ophthalmology, v. 118, issue 12, p. 1617-1625