Herpes Zoster Ophthalmicus

Overview

Herpes zoster ophthalmicus results from reactivation of varicella zoster virus (VZV) that remains latent in the ophthalmic division of the fifth cranial nerve (CNV1 or V1) following primary varicella infection.¹ The virus lies dormant in the sensory ganglion after primary chickenpox infection until reactivation occurs.² HZO is considered an ophthalmic emergency due to its potential for severe ocular complications, chronic pain, and vision loss.¹ In the United States, approximately one million cases of herpes zoster occur annually, with HZO representing 10% of all herpes zoster cases.^3,4 The incidence of herpes zoster is estimated at 3.2 per 1000 person-years.⁴ HZO is typically a clinical diagnosis based on the characteristic presentation of a unilateral vesicular eruption in the V1 distribution.¹

Epidemiology & Risk Factors

HZO commonly affects older adults and immunocompromised individuals.¹ Patients with HIV have the greatest risk of developing HZO compared with the general population.⁴ Additional risk factors include advancing age, use of immunosuppressive medications, and primary varicella infection in infancy or in utero.⁴ However, the incidence rate of herpes zoster has been rising over recent decades, with the average patient age at presentation declining.⁵

In the pediatric population, major risk factors include intrauterine exposure to varicella or primary varicella infection at a young age.⁶ HZO has also occurred in children who received varicella vaccination.⁶ Both healthy and immunocompromised children can be affected, though the majority of affected children are immunocompetent.⁶ HZO is a significant cause of blindness in the United States.³

Pathophysiology

Following primary varicella infection, VZV remains dormant in the sensory ganglion of the trigeminal nerve until reactivation triggers herpes zoster.² When reactivation involves the ophthalmic branch of the trigeminal nerve, HZO develops.² Ocular involvement is present in approximately 50% of affected patients.¹

Pathological changes in ocular structures occur through multiple mechanisms including direct viral invasion, secondary inflammation, and alterations of autoimmune mechanisms.² Recent imaging studies have demonstrated viral particles within keratocytes in cases of zoster stromal keratitis, providing evidence of direct corneal involvement.⁵ Early corneal manifestations include corneal dysesthesia and dendritiform keratopathy, which are typically self-limited.² However, smoldering disease can cause ongoing pathological changes in ocular structures.²

Clinical Presentation

HZO presents with a characteristic unilateral vesicular eruption in the dermatomes corresponding to the ophthalmic division of the trigeminal nerve.¹ The diagnosis is primarily clinical due to this classic presentation.^1,6

Ocular symptoms associated with HZO include severe chronic pain and potential vision loss.¹ The condition can manifest with varying presentations and complications.⁶ Acute keratitis is one of the most common ocular complications associated with HZO.⁵ Early corneal involvement is characterized by corneal dysesthesia and dendritiform keratopathy.²

Exam Findings

Physical examination reveals:

• Unilateral vesicular eruption in the V1 distribution
• Corneal dysesthesia in early disease²
• Dendritiform keratopathy as an early corneal manifestation²
• Signs of acute keratitis in affected patients⁵
• Evidence of zoster stromal keratitis in some cases⁵

The characteristic dermatomal distribution of the vesicular rash in the ophthalmic division typically allows for clinical diagnosis without extensive testing.¹

Classification

HZO is classified as a subtype of herpes zoster that specifically involves the V1 distribution of the trigeminal nerve.³ The condition occurs worldwide, usually in healthy adults but increasingly in immunocompromised patients.² Cases can be further characterized by the presence or absence of ocular involvement, with ocular manifestations present in approximately 50% of cases.¹

Differential Diagnosis

• Herpes simplex virus keratitis
• Other causes of unilateral vesicular rash
• Primary varicella infection
• Other viral keratitis
• Contact dermatitis affecting periorbital region
• Acute angle-closure glaucoma (for acute ocular pain)
• Other causes of dendritiform corneal lesions

Management

Timely treatment is imperative to minimize ocular morbidity in HZO.¹ Primary treatments include antivirals, analgesics, and anticonvulsants.⁴

Antiviral Therapy: Oral antiviral medications are the mainstay of treatment.⁵ Topical ganciclovir may be used to manage acute zoster keratitis that is unresponsive to oral antiviral therapy.⁵ Both oral and topical antiviral medications can play a role in managing acute disease.⁵ Antiviral agents have demonstrated success in resolving early signs and symptoms, though their role in preventing and treating late complications requires further study.²

Corticosteroids: In certain acute inflammatory processes, the benefits of steroid use outweigh the risk of reducing host immunity.² Steroids should be considered for specific inflammatory complications.

Surgical Intervention: Corneal complications of HZO sometimes require surgical intervention.² Management may require comanagement with pain specialists, psychiatrists, and infectious disease specialists.⁴

Pediatric Considerations: Children appear to have good vision recovery and resolution of symptoms if treated promptly and if they adhere to treatment regimens.⁶

Prevention: Vaccination against VZV is a primary prevention modality.⁴ Herpes zoster vaccinations are important for disease prevention.⁵ The recombinant vaccine (Shingrix) is now recommended by the Advisory Committee for Immunization Practices (ACIP) for healthy adults 50 years or older, with a trend toward using this vaccine over the live vaccine (Zostavax).³

Complications

HZO can result in a wide range of ocular complications that may lead to severe chronic pain and vision loss.¹ Acute zoster keratitis can lead to permanent vision loss if not managed appropriately.⁵ While early corneal dysesthesia and dendritiform keratopathy are typically self-limited, smoldering disease may cause pathological changes in ocular structures.²

In pediatric patients, irreversible vision loss can occur from uncommon complications such as optic neuritis.⁶ However, most children have good vision recovery when treated promptly with adherence to treatment regimens.⁶ Corneal complications sometimes necessitate surgical intervention.²

Clinical Pearls

• HZO is an ophthalmic emergency requiring prompt recognition and treatment to prevent vision-threatening complications¹
• Ocular involvement occurs in approximately 50% of HZO cases, making careful ophthalmologic evaluation essential¹
• The diagnosis is primarily clinical based on the characteristic unilateral vesicular eruption in the V1 dermatome¹
• Early diagnosis and management may help reduce potentially devastating complications including permanent vision loss⁵
• The incidence of herpes zoster has been rising while the average age at presentation is declining⁵
• Both healthy and immunocompromised children can develop HZO, with most affected children being immunocompetent⁶
• Prevention through vaccination is crucial, with the recombinant vaccine (Shingrix) now recommended over the live vaccine³

Common Pitfalls

• Delaying antiviral treatment while awaiting confirmatory testing, when the diagnosis is primarily clinical¹
• Failing to recognize that HZO can occur in immunocompetent individuals, not just those who are immunocompromised⁶
• Overlooking the possibility of HZO in pediatric patients, including those who received varicella vaccination⁶
• Inadequate follow-up for late complications, as the role of antivirals in preventing these remains under study²
• Underestimating the need for multidisciplinary management including pain specialists and infectious disease specialists⁴
• Assuming early self-limited findings will not progress to vision-threatening complications without appropriate treatment²
• Failing to provide patient education about vaccination for prevention, particularly in adults 50 years and older³