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Porcine Corneal Tissue Explant to Study the Efficacy of Herpes Simplex Virus-1 Antivirals
Published on: September 20, 2021
[Herpes Simplex Virus and Varicella-Zoster Virus Keratitis]
Abstract:
Herpesvirus infections of the cornea are among the leading infectious causes of corneal vision loss worldwide. Both herpes simplex virus (HSV) and varicella-zoster virus (VZV) play a major role in the development of corneal disease. Following primary infection, both viruses establish lifelong latency in sensory ganglia and may be reactivated by triggering factors such as ultraviolet (UV) exposure, stress, fever, surgery, or immunosuppression. Clinically, ocular herpesvirus infections present with a broad spectrum of manifestations, and early differentiation between these entities is essential for appropriate diagnosis, treatment, and prognosis. HSV keratitis is characterized by a recurrent course and includes epithelial, stromal, endothelial, and neurotrophic forms. Epithelial HSV keratitis results from active viral replication and typically presents as dendritic or geographic keratitis. Non-necrotizing stromal keratitis is predominantly caused by immune-mediated inflammatory responses without significant viral replication, whereas necrotizing stromal keratitis is thought to involve significant viral replication in combination with an excessive immune response. In HSV endotheliitis, both viral and immune-mediated mechanisms play a role. These clinical manifestations may be associated with keratouveitis, secondary glaucoma, iris atrophy, or corneal neovascularization. Recurrent episodes frequently lead to damage of the subbasal corneal nerve plexus, resulting in neurotrophic keratopathy. Varicella-zoster virus may also cause severe ocular complications in patients with herpes zoster ophthalmicus (HZO), including keratitis, uveitis, elevated intraocular pressure, neurotrophic corneal disease, and retinitis. Elderly and immunocompromised individuals are at particularly high risk of severe disease and postherpetic neuralgia. Diagnosis is primarily based on clinical findings and may be supported by corneal esthesiometry, in vivo confocal microscopy, and PCR-based virological testing. Polymerase chain reaction (PCR) analysis of corneal tissue or aqueous humor is particularly valuable in atypical or treatment-resistant cases. Management includes topical and systemic antiviral agents such as acyclovir, valacyclovir, ganciclovir, and famciclovir. Immune-mediated stromal and endothelial keratitis additionally require anti-inflammatory therapy. Neurotrophic forms require regenerative therapies such as autologous serum eye drops, amniotic membrane transplantation, or the recombinant human nerve growth factor cenegermin. Although no licensed vaccine against HSV is currently available, recombinant herpes zoster vaccination provides effective protection against VZV-associated ocular complications.
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