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The effect of flurbiprofen on herpes simplex virus type 1 stromal keratitis in mice
R L Hendricks1, C F Barfknecht, R D Schoenwald
1Department of Ophthalmology, University of Illinois, College of Medicine, Chicago 60612.
Abstract:
The use of steroidal compounds to reduce the inflammation and scarring associated with herpes simplex virus type 1 (HSV-1) stromal keratitis can result in severe exacerbation of the corneal disease. We compared the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen sodium with dexamethasone for the treatment of HSV-1 induced corneal stromal disease in an inbred mouse model. Stromal disease was induced by the direct intrastromal injection of HSV-1. A stromal opacity and corneal neovascularization (CNV) developed in 100% of the injected eyes, with no epithelial involvement until late in the course, when the stromal disease was quite severe, such that it was possible to test the effectiveness of drugs in animals with an intact epithelium. Dexamethasone treatment had a variable effect on the severity of disease, ranging from a significant reduction in severity to significant exacerbation of disease, compared with placebo-treated controls. The most frequent effect of dexamethasone treatment was a worsening of corneal stromal opacities and CNV. In contrast, treatment with the NSAID did not exacerbate HSV-1 stromal disease. Flurbiprofen treatment resulted in a significant reduction of the maximum intensity of stromal opacity in some experiments, whereas in other experiments the effect was not statistically significant. In vitro studies of the effect of the anti-inflammatory drugs on HSV-1 replication in Vero cells revealed that both dexamethasone and flurbiprofen inhibited HSV-1 replication in a dose-dependent manner. Flurbiprofen had a greater inhibitory effect, which appears to be due, at least in part, to a direct virucidal effect. Dexamethasone did not exhibit virucidal activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) like flurbiprofen did not worsen herpes simplex virus type 1 (HSV-1) stromal keratitis in mice, unlike dexamethasone, which often exacerbated the condition. Flurbiprofen also showed direct antiviral effects against HSV-1.
Area of Science:
- Ophthalmology
- Virology
- Pharmacology
Background:
- Steroidal compounds can worsen herpes simplex virus type 1 (HSV-1) stromal keratitis.
- HSV-1 induced stromal keratitis involves opacity and neovascularization without initial epithelial involvement.
Purpose of the Study:
- Compare the efficacy of flurbiprofen sodium (NSAID) and dexamethasone in treating HSV-1 induced corneal stromal disease.
- Evaluate the direct effect of these drugs on HSV-1 replication in vitro.
Main Methods:
- Induced HSV-1 stromal keratitis in an inbred mouse model via intrastromal injection.
- Administered flurbiprofen sodium and dexamethasone, comparing outcomes to placebo.
- Assessed corneal opacity, neovascularization, and epithelial integrity.
- Conducted in vitro studies on HSV-1 replication in Vero cells with drug treatments.
Main Results:
- Dexamethasone showed variable effects, frequently worsening corneal opacities and neovascularization.
- Flurbiprofen did not exacerbate HSV-1 stromal disease and sometimes reduced stromal opacity.
- Both drugs inhibited HSV-1 replication in vitro; flurbiprofen exhibited greater inhibition and virucidal activity.
Conclusions:
- Flurbiprofen is a safer alternative to dexamethasone for managing HSV-1 stromal keratitis due to lack of exacerbation.
- Flurbiprofen possesses direct antiviral and virucidal properties against HSV-1.
- Dexamethasone's exacerbating effect may be linked to its lack of virucidal activity.