A varicella-zoster vaccine was approved by the US Food and Drug Administration (FDA), after testing in 38,000 patients showed a 50% reduction in incidence of zoster and a 66% reduction in postherpetic neuralgia. The vaccine is recommended for immunocompetent individuals older than 60 years but was recently made available to those aged 50 years and older. This live, attenuated vaccine is similar to the childhood vaccine but contains a higher dose of the vaccine virus. There is concern that the average age of infection with herpes zoster will decline significantly with the widespread use of both vaccines and the consequential reduction in exposure to virus-shedding individuals, who inadvertently boost community immunity. This would most likely affect persons aged 20–50 years— those not currently covered by the vaccines—and could eventually lead to a change in age indications in the future. There are currently no clear recommendations concerning the use of the adult vaccine in patients with previous HZO, but the potential to reactivate or exacerbate HZO-related inflammation exists, as such cases have been reported. It is suggested that vaccinations be administered during an extensive quiet period.
The current recommendation for HZO is oral famciclovir 500 mg 3 times per day, valacyclovir 1 g 3 times per day, or acyclovir 800 mg 5 times per day for 7–10 days, best if started within 72 hours of the onset of skin lesions. Topical antiviral medications are not effective, except in the treatment of corneal epithelial mucoid plaques or more chronic epithelial disease. Intravenous acyclovir therapy (10 mg/kg every 8 hours) is indicated in patients at risk for disseminated zoster due to immunosuppression. Cutaneous lesions may be treated with moist warm compresses and topical antibiotic ointment. Topical corticosteroids and cycloplegics are indicated for keratouveitis. Oral corticosteroids on a tapering dosage are recommended by some for treating patients with HZO over age 60 to reduce early zoster pain and facilitate a rapid return to a normal quality of life. However, the use of oral corticosteroids is controversial; their use does not seem to affect the incidence or duration of postherpetic neuralgia.
Postherpetic neuralgia (PHN) may respond to capsaicin cream applied to the involved skin, but low doses of amitriptyline, desipramine, clomipramine, or carbamazepine may be necessary to control severe symptoms. Gabapentin (Neurontin) and pregabalin (Lyrica) have recently been shown to be efficacious in managing PHN. Aggressive lubrication with nonpreserved tears, gels, and ointments, combined with punctal occlusion and tarsorrhaphy as necessary, may be indicated for neurotrophic keratopathy. In a patient with significant pain, early referral to a pain management specialist should be considered.
Liesegang TJ. Herpes zoster ophthalmicus: natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115(2 Suppl):S3–S12.
Liesegang TJ. Varicella-zoster virus vaccines: effective, but concerns linger. Can J Ophthalmol. 2009;44(4):379–384.
Oxman MN, Levin MJ, Johnson GR, et al; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–2284.
Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50–59 years. Clin Infect Dis. 2012;54(7):922–928.
Epstein-Barr Virus Dacryoadenitis, Conjunctivitis, and Keratitis
PATHOGENESIS EBV is a ubiquitous herpesvirus that infects the majority of humans by early adulthood. Spread of EBV occurs by the sharing of saliva, and the virus results in subclinical infection in the first decade of life; if acquired later in life, it causes infectious mononucleosis. The virus remains latent in B lymphocytes and pharyngeal mucosal epithelial cells throughout life. Ocular disease is uncommon.
CLINICAL PRESENTATION EBV is the most common cause of acute dacryoadenitis, characterized by inflammatory enlargement of 1 or both lacrimal glands. Acute follicular conjunctivitis, Parinaud
oculoglandular syndrome, and bulbar conjunctival nodules have been reported in patients with acute infectious mononucleosis and may be the result of EBV infection. The 3 principal forms of EBV stromal keratitis are associated with EBV on the basis of a history of recent infectious mononucleosis and/or persistently high EBV serologic titers:
Type 1: multifocal subepithelial infiltrates that resemble adenoviral keratitis
Type 2: multifocal, blotchy, pleomorphic infiltrates with active inflammation (Fig 4-15) or granular ring-shaped opacities (inactive form) in anterior to midstroma
Type 3: multifocal deep or full-thickness peripheral infiltrates, with or without vascularization, that resemble interstitial keratitis due to syphilis
EBV-associated keratitis may be unilateral or bilateral and may, in select cases, appear similar to the keratitis induced by HSV, VZV, Lyme disease, adenovirus, or syphilis.
Figure 4-15 Epstein-Barr virus stromal keratitis. (Reprinted with permission from Chodosh J. Viral keratitis. In: Parrish RK, ed. The University of Miami Bascom Palmer Eye Institute Atlas of Ophthalmology. Boston: Current Medicine; 1999.)
MANAGEMENT Because of difficulty in isolating the virus, the diagnosis of EBV infection depends on the detection of antibodies to various viral components. During acute infection, first IgM and then IgG antibodies to viral capsid antigens (VCA) appear. Anti-VCA IgG may persist for the life of the patient. Antibodies to early antigens also rise during the acute phases of the disease and subsequently decrease to low or undetectable levels in most individuals. Antibodies to EBV nuclear antigens appear weeks to months later, providing serologic evidence of past infection. Acyclovir is not effective treatment for the clinical signs and symptoms of infectious mononucleosis, but the impact of antiviral therapy on the corneal manifestations of EBV infection remains unknown. Corticosteroids may be effective in patients with reduced vision due to apparent EBV stromal keratitis, but they should not be administered without a prophylactic antiviral if HSV infection is a possibility.
Chodosh J. Epstein-Barr virus stromal keratitis. Ophthalmol Clin North Am. 1994;7(4):549–556.
Cytomegalovirus Keratitis and Anterior Uveitis
PATHOGENESIS Cytomegalovirus (CMV) is a ubiquitous herpesvirus that infects over 90% of humans by age 80. Spread of CMV occurs through the sharing of saliva, ingestion of breast milk, or sexual contact. CMV results in subclinical infection in children and a nonspecific febrile illness lasting 1–3 weeks in adults. A viremia transmits the virus to the bone marrow, where it becomes latent in CD 34+
myeloid progenitor cells until these cells are activated, which allows expression and shedding of the virus.
CLINICAL PRESENTATION In the eye, CMV has been most commonly associated with a sectoral, necrotizing retinitis that is seen almost exclusively in AIDS and other immunocompromised states. Few anterior segment complications were previously associated with CMV retinitis, with the exception of thin stellate keratic precipitates. In rare instances, epithelial and stromal CMV keratitis have been described, usually for cases in which CMV was undiagnosed prior to keratoplasty. Recently, CMV has been increasingly identified as a significant cause of anterior uveitis and corneal endotheliitis (Fig 4-16). This is probably due, in part, to improved diagnostic acumen. The anterior uveitis is characterized by an acute or chronic iritis, with moderate to severe rises in IOP that are variably responsive to topical corticosteroids. The addition of keratic precipitates, endothelial cell loss, and diffuse or local corneal edema suggests CMV endotheliitis. These presentations are often misdiagnosed as HSV-related endotheliitis, trabeculitis, or Posner-Schlossman syndrome and can be distinguished only by their response to therapy and by results of laboratory investigation.
Figure 4-16 Clusters of keratic precipitates in cytomegalovirus corneal endotheliitis. (Courtesy of Cornea Service, Paulista School of
Medicine, Federal University of São Paulo.)
LABORATORY EVALUATION Laboratory confirmation of disease is usually accomplished through PCR testing of aqueous humor for CMV. Aqueous humor is obtained by an anterior chamber tap, which must be performed during an episode of active disease. Concomitant testing for other herpesviruses can also be performed. Contemporaneous serum samples may be tested to confirm that the viremia is local rather than systemic. CMV may also be diagnosed through histologic examination of biopsy specimens.
MANAGEMENT CMV-associated anterior segment disease is treated with ganciclovir and is not responsive to famciclovir, acyclovir, or its derivatives. Resistance of a presumed HSV infection to these agents should raise the suspicion of CMV. The optimal treatment of CMV-associated anterior segment disease is unknown, but treatment with oral valganciclovir 900 mg twice daily (with the possibility of lower maintenance dosing) is effective. Valganciclovir may be poorly tolerated and, unfortunately, recurrence of disease with withdrawal of the medication is common. Alternatives include ganciclovir implants and topical ganciclovir, but despite some suggestion of effect, the role of topical therapy is controversial. Recurrence can occur after keratoplasty. The role of corticosteroids is unclear, as there is some suggestion that steroid use may prolong or worsen CMVassociated anterior segment disease. Corticosteroids should therefore be used judiciously in this