Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations.

In vitro synergism of trifluorothymidine and ganciclovir against HSV-1.

Purpose: To determine whether trifluorothymidine (TFT) and ganciclovir (GCV) are synergistic against herpes simplex virus type 1 (HSV-1).

Methods: TFT and GCV activity against 12 strains of HSV-1 (including an acyclovir-resistant strain) was measured by plaque-forming unit (PFU) inhibition. Cellular toxicity was assessed with an MTT dye reduction assay.

Effect of high versus low oral doses of valacyclovir on herpes simplex virus-1 DNA shedding into tears of latently infected rabbits.

Purpose: To assess the effect of high doses of valacyclovir (VCV) on HSV-1 DNA shedding into tears of latently infected rabbits.

Methods: Three oral doses of VCV were tested. Corneas were inoculated with HSV-1, and latent infection was allowed to establish.

A double-blind placebo-controlled study to evaluate valacyclovir alone and with aspirin for asymptomatic HSV-1 DNA shedding in human tears and saliva.

Purpose: To test the effect of valacyclovir alone and with aspirin on the asymptomatic shedding of HSV-1 DNA in tears and saliva of healthy individuals. METHOD. The subjects (n = 45) were randomized into three groups without regard to age, sex, or race.

WITHDRAWN: Synergistic interaction of aciclovir and a helicase-primase inhibitor, BAY 57-1293, against herpes simplex virus type 1.

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Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infection.

Purpose: The aim of this study was to evaluate the effect of BAY 57-1293, a helicase-primase inhibitor, on herpes simplex virus type 1 (HSV-1) reactivation in mice and its efficacy on established disease in rabbits.

Methods: BALB/c mice latent for McKrae-strain HSV-1 were reactivated via heat stress, treated with BAY 57-1293, and their corneas were swabbed for virus or the trigeminal ganglia (TG) obtained for quantification of viral DNA. New Zealand white rabbits were infected and treated topically or orally in comparison with trifluridine or valacyclovir.

Preliminary in vitro evaluation of 2-octyl cyanoacrylate (Dermabond) to seal corneal incisions.

Objective: To compare the efficacy of Dermabond with conventional nylon sutures for sealing linear corneal incisions.

Methods: A keratome knife was used to create a 4-mm full-thickness linear corneal incision anterior to the limbal arcade in 20 fresh pig eyes. The incision was sealed with Dermabond tissue adhesive or closed with 10-0 nylon sutures.

Immunohistochemical analysis of orbital connective tissue specimens of patients with active Graves ophthalmopathy.

Purpose: To explore the immune mechanism of Graves ophthalmopathy (GO) by analyzing infiltrating cells in orbital connective tissue (OCT) specimens of patients with active GO using immunohistochemical methods.

Methods: Five OCT specimens obtained from patients with active GO and five control specimens obtained from forensic cadavers who died from nonmedical reasons were stained with anti-CD3, CD4, CD8, CD45RO, HLA-Dr, CD25, and TNF-alpha monoclonal antibodies. Positively stained cells were counted and results were interpreted as cell counts/mm2.

Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation.

Recurrent herpes virus infection, in which the virus reactivates from the nervous system and causes painful lesions in peripheral tissues, is a significant clinical problem. Our recent studies showing that the amount of cyclooxygenase 2 (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib, have indicated that the prostaglandin synthesis pathway--and in particular COX-2--may be an intermediate in the pathway to herpes viral reactivation. To further study this process, we infected the corneas of mice using topical application to a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1 (HSV-1) latency to be established in the trigeminal ganglia.

HSV-1 DNA in tears and saliva of normal adults.

Purpose: To assess the frequency of shedding of herpes simplex virus type 1 (HSV-1) DNA in tears and saliva of asymptomatic individuals.

Methods: Fifty subjects without signs of ocular herpetic disease participated. Serum samples from all subjects were tested for HSV IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and for HSV-1 by neutralization assay.

Acetylsalicylic acid reduces viral shedding induced by thermal stress.

Purpose: To investigate the effect of acetylsalicylic acid on ocular shedding of herpes simplex virus type 1 (HSV-1).

Materials And Methods: Mice that were latent for the McKrae strain of HSV-1 were treated with acetylsalicylic acid, a nonspecific inhibitor of cyclooxygenases, either prophylactically or at the time of heat stress-induced viral reactivation. The effect of the drug on viral shedding in the tear film, infectious virus in the cornea and trigeminal ganglion, and viral DNA in the cornea and trigeminal ganglion was determined.

Corneal healing after uncomplicated LASIK and its relationship to refractive changes: a six-month prospective confocal study.

Purpose: To investigate corneal healing and the factor(s) possibly responsible for refractive changes after laser in situ keratomileusis (LASIK).

Methods: Twenty eyes of 10 patients who underwent LASIK for myopia were examined clinically and by real-time confocal microscopy for 6 months. Epithelial and posterior stromal thicknesses and the thickness of the keratocyte activation zone were measured, and refractive changes were compared with these values.

The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study.

Purpose: To investigate whether conjunctival inflammation represents a primary event in the pathogenesis of keratoconjunctivitis sicca or whether it is a secondary inflammatory reaction caused by enhanced mechanical irritation as a result of surface dryness and whether anti-inflammatory drops (corticosteroids and nonsteroidal anti-inflammatory) have therapeutic effects and are similar.

Design: Single-masked, randomized, prospective clinical trial.

Methods: Thirty-two keratoconjuctivitis patients with or without Sjögren syndrome were included in the study.

The effect of roscovitine on herpetic keratitis.

To determine the effect of roscovitine, a potent antiviral in tissue culture administered intramuscularly to rabbits or by eye drops to mice for the treatment of herpetic keratitis this study was commenced.New Zealand white rabbits infected with McKrae strain herpesvirus (HSV-1) were treated twice a day with 10mg Roscovitine or vehicle from day 3 to 7, or 1% trifluridine eye drops five times a day. Severity of keratitis was graded daily by a masked observer.