As a class, viruses are strictly intracellular parasites, relying on the host cell for their replication. Herpesviruses, which are large-enveloped, double-stranded DNA viruses, are some of the most common human infectious agents and are responsible for a wide spectrum of acute and chronic diseases. Herpesviruses of interest to the ophthalmologist are the herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). There are 9 recognized types of human herpesviruses. Type 1 is HSV-1; type 2 is HSV-2; type 3 is VZV; type 4 is EBV; type 5 is CMV; human herpesvirus types 6A, 6B, and 7 are known as HHV-6A, HHV-6B, and HHV-7, respectively; and type 8 (HHV-8) is associated with Kaposi sarcoma.
Herpes simplex virus (HSV) types 1 and 2 are members of the Herpesviridae family. HSV type 1 and 2 infections differ in severity and clinical manifestation; many persons with HSV antibodies are asymptomatic. Latent infection of sensory and autonomic ganglia can occur. Reactivation of HSV from the trigeminal ganglia may be associated with asymptomatic excretion or with the development of mucosal herpetic ulceration. Serologic testing, DNA PCR testing, and viral culture can help diagnose difficult cases, particularly CNS infections.
HSV-1 is associated with mucocutaneous infections of the pharynx, skin, oral cavity, vagina, eye, and brain. Ophthalmic infection most often manifests as corneal dendritic or stromal disease but may present as acute retinal necrosis. (The ocular manifestations of HSV infection are discussed in more detail in BCSC Section 8, External Disease and Cornea, and Section 9, Uveitis and Ocular Inflammation.) Herpes encephalitis carries a 10%–20% mortality rate. HSV-2 infection is an important sexually transmitted disease that is associated with genital infections, aseptic meningitis, and congenital infection. Neonatal herpes infection affects around 1 in 3500 babies born in the United states and is defined by vertical transmission from mother to infant within the first 28 days of life. Neonatal herpes infection involves multiple systems and, if untreated, has a mortality rate around 25%.
The drug of choice for treating acute systemic infections is acyclovir. Localized disease can be treated with oral acyclovir. Topical treatment of skin or mucocutaneous lesions with acyclovir ointment decreases the healing time. Oral acyclovir can also be used prophylactically for severe and recurrent genital herpes. Long-term suppressive oral acyclovir (400 mg twice a day) also reduces the recurrence of herpes simplex epithelial keratitis and stromal keratitis. Intravenous acyclovir is used to treat herpes encephalitis.
Famciclovir and valacyclovir are also approved in the United States for the treatment of herpes zoster and herpes simplex infections. Compared with acyclovir, these agents have better bioavailability, achieve higher blood levels, and require less frequent dosing. HSV is also sensitive to vidarabine. Cidofovir or foscarnet can also be used to treat acyclovir-resistant herpes simplex.
Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence-based review. Arch Intern Med. 2008;168(11):1137–1144.
Chau Tran TH, Cassoux N, Bodaghi B, Lehoang P. Successful treatment with combination of systemic antiviral drugs and intravitreal ganciclovir injections in the management of severe necrotizing herpetic retinitis. Ocul Immunol Inflamm. 2003;11(2):141–144.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.