Ophthalmology – Herpes Zoster Ophthalmicus

Basics

Description

Herpes zoster ophthalmicus (HZO) results from reactivation of latent varicella-zoster virus (VZV) within the ophthalmic division of the trigeminal nerve. It classically produces an acute, painful, unilateral vesicular eruption involving the V1 dermatome.

Ocular inflammation may involve the eyelids, conjunctiva, episclera, sclera, cornea, anterior chamber, iris, retina, optic nerve, or ocular motor nerves.

Occasionally, ocular VZV disease occurs without the characteristic skin eruption. This presentation is called zoster sine herpete.

HZO is clinically important because ocular complications can arise during the acute eruption or weeks to months later, and some may cause permanent visual loss.

Epidemiology

The risk of herpes zoster increases substantially with age because of declining VZV-specific cellular immunity.

HZO represents reactivation involving the ophthalmic division of the trigeminal nerve and occurs more often in older adults and immunocompromised individuals.

Risk Factors

The strongest risk factor is increasing age.

Other important risk factors include impaired cellular immunity due to HIV infection, malignancy, organ transplantation, immunosuppressive medication, chemotherapy, or other causes of immunodeficiency.

General Prevention

Vaccination is the principal preventive measure.

Current CDC recommendations use the recombinant zoster vaccine, Shingrix, rather than the older live Zostavax vaccine. Two doses of Shingrix are recommended for immunocompetent adults 50 years and older and for adults 19 years and older who are or will be immunodeficient or immunosuppressed. Previous herpes zoster does not eliminate the indication for vaccination. Zostavax is no longer available in the United States. 

Vaccination is preventive and is not a treatment for an active episode of HZO.

Pathophysiology

After primary varicella infection, VZV establishes latency within sensory ganglia.

HZO occurs when latent virus reactivates in the trigeminal ganglion, particularly along the ophthalmic division of cranial nerve V.

The virus travels along sensory axons toward the skin and ocular structures, producing a combination of direct viral injury, vascular inflammation, and host immune-mediated tissue damage.

Declining VZV-specific cellular immunity with increasing age helps explain the rising incidence of zoster in older adults.

Diagnosis

History

The illness may begin with a prodrome consisting of fever, malaise, headache, fatigue, and neuropathic pain within the affected dermatome.

Pain may precede the rash by several days and can be described as:

burning, aching, stabbing, lancinating, itching, or hypersensitivity to touch.

The characteristic rash is unilateral and respects the midline.

Patients should be questioned about visual blur, photophobia, ocular redness, diplopia, floaters, reduced vision, and severe eye pain.

Skin Findings

The V1 rash evolves from erythematous macules and papules into vesicles, followed by pustules and eventually crusting.

The forehead, scalp, upper eyelid, and periocular skin may be involved.

Lesions involving the tip, side, or root of the nose suggest involvement of the nasociliary branch of V1 and increase concern for ocular involvement. This is traditionally called Hutchinson sign, although ocular disease can still occur when the sign is absent.

Ophthalmic Examination

All patients with HZO should undergo careful ocular assessment, particularly when ocular symptoms are present. Contemporary reviews recommend ophthalmologic evaluation because potentially serious ocular disease may accompany or follow the rash. 

Examination should include visual acuity, pupils, slit-lamp examination, intraocular pressure, corneal sensation, ocular motility, and dilated fundus examination when indicated.

Early Ocular Findings

Eyelids

The eyelids may show edema, erythema, vesicles, crusting, and temporary ptosis.

Marked swelling may occasionally make examination difficult.

Conjunctiva

Conjunctival involvement may cause hyperemia, follicular or papillary reaction, petechial hemorrhages, vesicular lesions, or pseudomembranes.

Episclera and Sclera

Patients may develop episcleritis, scleritis, sclerokeratitis, or posterior scleritis.

Cornea

Early corneal manifestations include punctate epithelial keratitis and pseudodendrites.

Unlike the classic dendrites of herpes simplex, VZV pseudodendrites are typically elevated epithelial lesions and generally do not have the same classic terminal bulbs.

Later stromal involvement may produce nummular keratitis, stromal inflammation, endothelial disease, or disciform edema.

Anterior Uveitis

HZO can cause a granulomatous or nongranulomatous anterior uveitis with anterior chamber cells, keratic precipitates, and elevated intraocular pressure.

A characteristic late finding is sectoral iris atrophy, caused in part by ischemic damage to iris vessels.

Secondary ocular hypertension or glaucoma may result from trabeculitis, chronic inflammation, synechial changes, or corticosteroid treatment.

Late Corneal Disease

Ocular complications may begin or recur after the skin eruption has resolved.

Late manifestations include delayed pseudodendrites, mucous plaque keratitis, neurotrophic keratopathy, persistent epithelial defects, stromal scarring, chronic edema, lipid deposition, band keratopathy, and corneal ulceration.

Reduced corneal sensation is particularly important because it may result in severe epithelial disease with surprisingly little pain.

Neurotrophic Keratopathy

Damage to trigeminal sensory innervation can substantially reduce corneal sensation.

The resulting neurotrophic cornea may develop:

• Persistent epithelial defects
• Sterile ulceration
• Stromal melting
• Secondary infection
• Corneal perforation

Patients with reduced corneal sensation require particularly careful long-term follow-up.

Retina and Optic Nerve

Serious posterior segment complications include retinal vasculitis, optic neuropathy, acute retinal necrosis (ARN), and progressive outer retinal necrosis (PORN).

ARN is a rapidly progressive necrotizing retinitis accompanied by retinal vasculitis and inflammation.

PORN is particularly associated with profound immunosuppression and may progress extremely rapidly with relatively little intraocular inflammation.

Both require urgent retina specialist evaluation and systemic plus local antiviral therapy.

Neuro-Ophthalmic Manifestations

HZO may affect ocular motor nerves and produce transient or persistent diplopia and ophthalmoplegia.

Cranial nerves III, IV, and VI may be involved.

Rarely, multiple cranial neuropathies may occur in association with orbital apex inflammation, vasculitis, or brainstem disease.

Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is persistent neuropathic pain after the acute rash has healed.

Symptoms may include:

• Constant burning or aching
• Sudden electric or lancinating pains
• Allodynia, where light touch causes pain
• Persistent itching or dysesthesia

Risk increases considerably with age.

Diagnostic Tests and Interpretation

Laboratory Testing

Typical HZO with a characteristic dermatomal rash is primarily a clinical diagnosis, and routine laboratory confirmation is unnecessary.

Testing for an underlying immunodeficiency, including HIV, should be considered when disease occurs in an unusually young patient, is severe or disseminated, or when other clinical features suggest immunosuppression.

PCR

When zoster sine herpete is suspected or when the cause of anterior uveitis, retinitis, or other ocular inflammation is uncertain, PCR of aqueous or vitreous fluid for VZV DNA can help establish the diagnosis.

Differential Diagnosis

Important differential diagnoses include herpes simplex infection, orbital cellulitis, contact dermatitis such as poison ivy exposure, bacterial skin infection, other causes of anterior uveitis, and other necrotizing retinitides.

Treatment

Systemic Antiviral Therapy

Systemic antiviral treatment is the cornerstone of HZO management.

Therapy should be initiated as soon as possible, ideally within 72 hours of rash onset. Early treatment reduces viral replication and is associated with faster rash resolution and fewer ocular complications. Because HZO itself carries a high risk of complications, antiviral treatment may still be appropriate when a patient presents after 72 hours, particularly if new lesions are appearing or ocular disease is present. 

Common oral regimens in immunocompetent adults include:

Valacyclovir 1,000 mg three times daily, famciclovir 500 mg three times daily, or acyclovir 800 mg five times daily, generally for approximately 7–10 days depending on clinical circumstances. Renal adjustment is required when appropriate. 

Treatment should not be delayed while awaiting ophthalmology evaluation.

Renal Considerations

Acyclovir, valacyclovir, and famciclovir require dose adjustment in patients with impaired renal function.

Older adults are particularly vulnerable to drug accumulation, acute kidney injury, and neurotoxicity when renal function is reduced or hydration is inadequate.

Skin Care

Crusted or secondarily infected skin lesions may be treated with appropriate local wound care.

Topical antibiotic ointment may be used when there is concern for secondary bacterial infection of open or crusted lesions.

Ocular Surface Treatment

Lubricating artificial tears and ointment may help when ocular surface irritation or dry eye is present.

Patients with reduced corneal sensation require more aggressive lubrication and close observation for epithelial breakdown.

Topical Corticosteroids

Topical corticosteroids may be appropriate for stromal keratitis, endotheliitis, scleritis in selected circumstances, or anterior uveitis, but they should be used under ophthalmologic supervision and generally with adequate systemic antiviral treatment.

Steroids should not be used indiscriminately for epithelial disease.

Patients receiving corticosteroids require monitoring of intraocular pressure.

Cycloplegia

Cycloplegic agents may be used for significant anterior uveitis to reduce ciliary spasm, relieve pain, and prevent posterior synechiae.

Secondary Glaucoma

Elevated intraocular pressure should be treated with appropriate pressure-lowering medication.

Persistent or difficult-to-control glaucoma may require referral to a glaucoma specialist.

Postherpetic Neuralgia Treatment

Management of PHN may involve agents used for neuropathic pain, such as gabapentin or pregabalin, selected antidepressants, topical lidocaine, and other analgesic strategies.

Persistent or severe neuralgia may warrant referral to neurology or a pain specialist.

Neurotrophic Corneal Disease

Management depends on severity and may include preservative-free lubrication, autologous serum tears, protective contact or scleral lenses in selected cases, amniotic membrane, punctal occlusion, tarsorrhaphy, or other ocular surface procedures.

Corneal thinning or melting requires urgent corneal specialist management.

Acute Retinal Necrosis and PORN

Suspected ARN or PORN is an ophthalmic emergency.

Treatment generally requires aggressive systemic antiviral therapy and frequently intravitreal antiviral therapy.

Immediate retina specialist involvement is essential because progression can be rapid and may lead to retinal detachment and profound vision loss.

Surgery and Other Procedures

A tarsorrhaphy may be necessary for persistent neurotrophic epithelial defects or ulceration that fails conservative treatment.

Small corneal perforations may sometimes be managed with tissue adhesive and protective measures.

Amniotic membrane transplantation or conjunctival flap procedures may be considered for persistent epithelial defects, thinning, or neurotrophic ulceration.

Corneal transplantation may eventually be necessary for visually significant scarring or structural failure, although surgery in a severely neurotrophic eye carries increased risk.

Inpatient Considerations

Hospital admission may be necessary for patients with disseminated zoster, severe immunosuppression, inability to take or administer oral medication, serious neurologic complications, severe posterior segment involvement, or need for intravenous antiviral therapy.

Airway, neurologic, systemic, and ocular complications should be addressed according to severity.

Follow-Up

The timing of follow-up depends on ocular involvement.

Patients with active ocular disease frequently require reevaluation within several days, followed by visits determined by corneal, uveitic, retinal, and intraocular pressure findings.

Long-term follow-up may be necessary because keratitis, uveitis, glaucoma, neurotrophic keratopathy, and retinal disease can develop or recur after the cutaneous rash has resolved.

Patient Education

Patients should understand that the skin eruption may improve while ocular complications continue to develop.

They should seek urgent assessment for new blurred vision, photophobia, increasing redness, worsening eye pain, diplopia, floaters, flashes, or sudden loss of vision.

Patients should also be informed about vaccination after the acute illness has resolved. Current CDC guidance recommends Shingrix even for people who have previously had shingles. 

Prognosis

In otherwise healthy individuals, formation of new skin lesions generally stops within several days and the rash subsequently crusts and heals.

The ocular prognosis varies with the structures involved.

Patients with uncomplicated epithelial disease may recover well, while those developing stromal scarring, glaucoma, neurotrophic keratopathy, optic neuropathy, or necrotizing retinitis can sustain permanent visual loss.

Complications

Important ophthalmic complications include corneal scarring, chronic keratitis, neurotrophic ulceration, corneal perforation, secondary bacterial keratitis, cataract, glaucoma, chronic anterior uveitis, retinal necrosis, retinal detachment, optic neuropathy, ocular motor nerve palsies, and permanent visual impairment.

Systemic and neurologic complications include postherpetic neuralgia and an increased risk of cerebrovascular events after herpes zoster.

The combination of early systemic antiviral treatment and appropriate ophthalmic follow-up is central to reducing preventable morbidity.