Following primary infection, VZV establishes latency in sensory ganglia. Zoster (shingles) represents endogenous reactivation of latent virus in individuals with a waning level of immunity to infection. Most patients with zoster are in their sixth to ninth decades of life, and the majority are healthy, with no specific predisposing factors. However, zoster is more common in patients on immunosuppressive therapy; in those with a systemic malignancy, a debilitating disease, or HIV infection; and after major surgery, trauma, or radiation therapy. Herpes zoster in otherwise healthy children has been described in the literature.
Zoster manifests as a painful vesicular dermatitis typically localized to a single dermatome on the thorax or face. Initially, affected patients may report fever and malaise and experience warmth, redness, and increased sensation in the affected dermatome. The most commonly affected dermatomes are on the thorax (T3 through L3) and those supplied by CN V. The ophthalmic division of the trigeminal nerve is affected more often than the maxillary and mandibular branches, and its involvement is referred to as herpes zoster ophthalmicus (HZO) (Fig 9-13). A maculopapular rash, followed by vesicles and then pustules, is characteristic. Zoster dermatitis may result in large scabs that resolve slowly and leave significant scarring. Neurotrophic keratopathy and sectoral iris atrophy are characteristic. Inflammation of almost any ocular tissue can occur and recur in HZO.
Zoster dermatitis is accompanied by pain and dysesthesia. The pain usually decreases as lesions resolve; however, neuralgia in the affected dermatome can continue for months to years. The severity of pain ranges from mild to incapacitating. Ocular involvement occurs in more than 70% of patients with zoster of the first division of CN V and may appear in association with any branch, including the nasociliary, frontal, or lacrimal branches. Ophthalmic complications also may occur with zoster of the second (maxillary) division of CN V. In immunosuppressed patients, zoster may involve more than 1 branch of the trigeminal nerve at the same time; after reactivation, disease may be chronic, and there may be multiple recurrences. See BCSC Section 2, Fundamentals and Principles of Ophthalmology, for discussion of the innervation of the eye and face.
Eyelid vesicular eruption can lead to secondary bacterial infection, eyelid scarring, marginal notching, loss of cilia, trichiasis, and cicatricial entropion or ectropion. Scarring and occlusion of the lacrimal puncta or canaliculi may occur. Episcleritis or scleritis associated with zoster may be nodular, zonal, or diffuse.
Both punctate and dendritic epithelial keratitis caused by viral replication in corneal epithelium are common manifestations of ophthalmic zoster. Herpes zoster pseudodendrites (distinguished from the true dendrites of HSV corneal disease, which have a central epithelial ulceration) form branching or “medusa-like” lesions that resemble raised mucous plaques, stain minimally with fluorescein and rose bengal, and have blunt rather than bulbous ends. The elevated dendritiform mucous plaques may occur on the cornea weeks to months after resolution of the skin lesions. These may be chronically culture-positive for VZV in patients with AIDS. Diminished corneal sensation occurs in up to 50% of patients. Nummular corneal infiltrates are said to be characteristic of zoster stromal keratitis (Fig 9-14), but the interstitial keratitis, disciform keratitis, and anterior uveitis with increased IOP in HZO are clinically indistinguishable from those caused by HSV infection. Chronic corneal stromal inflammation can lead to corneal vascularization, lipid keratopathy (Fig 9-15), and corneal opacity. Corneal anesthesia may be profound, and neurotrophic keratopathy due to HZO can be extremely difficult to manage.
Figure 9-13 Herpes zoster ophthalmicus (HZO).
(Courtesy of Vincent P. deLuise, MD.)
Figure 9-14 Nummular keratitis of HZO.
(Courtesy of Rhea L. Siatkowski, MD.)
Figure 9-15 Lipid keratopathy following HZO.
(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.)
Focal choroiditis, occlusive retinal vasculitis, and retinal detachment have been reported. Ipsilateral acute retinal necrosis (ARN) temporally associated with HZO is uncommon.
Orbital or central nervous system involvement as a result of an occlusive arteritis may lead to eyelid ptosis, orbital edema, and proptosis. Papillitis or retrobulbar optic neuritis may also develop. Cranial nerve palsies, when meticulously investigated, have been reported to occur in up to one-third of cases of HZO, with CN III (oculomotor) most commonly affected. Cranial nerve involvement may occur within the orbit or the cavernous sinus. Systemic dissemination is unusual in immunocompetent patients but can occur in up to 25% of those who are immunocompromised.
Two varicella-zoster vaccines are approved by the US Food and Drug Administration (FDA) for the prevention of shingles: a live, attenuated zoster vaccine has been available since 2006, and a recombinant zoster vaccine has been in use since 2017. The Centers for Disease Control and Prevention (CDC) recommends the recombinant vaccine, given in 2 doses separated by 2 to 6 months, as the preferred shingles vaccine for immunocompetent adults aged 50 years and older; this vaccine decreases the risk of VZV by more than 90%. Studies indicate that the incidence of herpes zoster rises with increasing age, starting from age 50 years. There is concern that the average age at infection with herpes zoster will become significantly lower 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. 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.
Oral antiviral therapy for HZO was found in randomized clinical trials to reduce viral shedding from vesicular skin lesions, reduce the chance of systemic dissemination of the virus, and decrease the incidence and severity of the most common ocular complications. Oral antiviral therapy may reduce the duration and severity if not the incidence of postherpetic neuralgia (PHN), if begun within 72 hours of the onset of symptoms. There are also reports to suggest that initiating antiviral therapy after 72 hours, especially in the presence of new vesicles, is beneficial.
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, used with a tapering dosage, are recommended by some for treating patients older than 60 years with HZO to reduce the pain associated with early zoster 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 PHN.
Postherpetic neuralgia 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 and pregabalin have been shown to be efficacious in managing PHN. Aggressive lubrication with nonpreserved artificial tears, gels, or ointments, combined with punctal occlusion and tarsorrhaphy as necessary, may be indicated for neurotrophic keratopathy. For a patient with significant pain, early referral to a pain management specialist should be considered.
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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.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.