Infection from the varicella-zoster virus (VZV) most commonly occurs in childhood and is spread by airborne, droplet, and contact transmission. Herpes zoster results from reactivation of the latent VZV within a sensory nerve ganglion, often presenting decades after the initial infection. The disease typically presents as a unilateral maculopapular or vesicular rash in a single dermatomal distribution. Herpes zoster ophthalmicus (HZO) is defined as the viral involvement of the ophthalmic division (V1) of the trigeminal cranial nerve (V). While the diagnosis of HZO does not necessarily imply eye involvement, ocular disease occurs in about 50% of HZO cases. Ocular manifestations can include conjunctivitis, uveitis, episcleritis, keratitis, and retinitis. The condition is considered an ophthalmologic emergency due to the risk of vision loss if not quickly identified and treated early in the disease course.
In those with a history of prior infection, the VZV normally lies dormant within a dorsal root ganglion. In a healthy individual, immunity acquired from the initial infection allows suppression of the virus. However, often in the setting of weakened immunity, the virus may reactivate in the form of herpes zoster, also known as shingles. HZO specifically refers to a reactivated VZV infection involving the V1 nerve division after having lied dormant within the trigeminal nerve ganglion (also known as the Gasserian ganglion). V1 is subdivided into three branches: the frontal nerve branch, the nasociliary nerve branch, and the lacrimal nerve branch. Any or all of these nerve branches may be affected in the case of HZO. The disease typically results in ocular and facial lesions with potential progression to more serious complications. The main risk factors for HZO include age over 50-years-old and immunocompromised status (e.g., history of HIV, autoimmune diseases requiring corticosteroids or other immunosuppressants, organ or bone marrow transplant, or chemotherapy treatment). Other chronic diseases, acute illnesses, and physical and emotional stressors can also precipitate HZO.
In the United States, herpes zoster affects about 1 per 1000 individuals annually. However, in the over 60-years population, the incidence is closer to 1 per 100 individuals. The incidence in older adults is lower in those who have received either the live attenuated or inactivated recombinant zoster vaccines. Among patients diagnosed with herpes zoster, some epidemiological studies estimate about 8% to 20% are complicated by HZO, with many of those cases resulting in ocular involvement.
HZO follows the typical pathogenic process as herpes zoster. VZV is a double-stranded DNA virus that initially invades the upper respiratory tract via virus-laden respiratory droplets, where it replicates and invades adjacent lymph nodes. After about a week, the virus disseminates and progresses to a secondary cutaneous infection with vesicle eruption occurring several days later. Following the primary infection, the virus follows a retrograde pathway along axons towards sensory nerve ganglia, where it enters the latent phase. In the reactivation phase, the virus moves in an anterograde fashion towards superficial tissue where it reemerges as herpes zoster.
Patients with HZO typically present with prodromal pain in a unilateral V1 dermatomal distribution, followed by an erythematous vesicular or pustular rash to the same area. Pain is neuropathic, and patients may describe the sensation as "burning" or "shooting", sometimes accompanied by paresthesias. Additionally, the herpetic rash may be preceded by constitutional symptoms such as fever, fatigue, malaise, and headaches. The presence of herpetic lesions around the tip of the nose is known as the Hutchinson sign. The presence of Hutchinson sign indicates nasociliary branch involvement of V1, which confers a higher risk for ocular involvement. The nasociliary branch innervates the tip of the nose and cornea, as well as other ocular structures.
The physical exam begins with an external evaluation of lesion distribution, including the eyelids and scalp. The rash often appears maculopapular before transitioning to vesicles and pustules that ultimately rupture and scab over. Although the rash is usually limited to a single unilateral dermatome, immunocompromised patients may develop disseminated disease, with a possible bilateral presentation. Particular attention should be paid to eyelid involvement, which is frequently associated with blepharitis, conjunctivitis, and episcleritis. Ptosis is rare but may occur in response to marked inflammation. A thorough ocular exam is required and must include visual acuity, slit-lamp examination with fluorescein staining, and ocular tonometry. A thorough dilated funduscopic exam is also necessary.
HZO is primarily a clinical diagnosis based on history and classic findings on physical and slit-lamp examination. Additional procedures, such as ocular tonometry and corneal esthesiometry, may be performed for a more thorough evaluation to assess for complications. Other diagnostic tests, such as viral cultures, polymerase chain reaction (PCR), and antibody testing, are rarely required to establish a diagnosis of HZO. For patients with disseminated herpes zoster (disease involving multiple dermatomes), severe illness, or those with significant risk factors, it is reasonable to consider HIV testing. Additional laboratory tests and imaging are seldom warranted.
Treatment for HZO includes prompt initiation of antiviral agents for all patients, as well as supportive care for symptom management. Other adjunct therapies, such as antibiotics, topical or systemic corticosteroids, and corneal epithelial debridement, are considered on a case-by-case basis.
The prognosis of HZO is highly variable and largely dependent on the patient’s risk factors, the timing of treatment, and the aggressiveness of the disease. There is limited data on the morbidity and mortality rates of HZO. However, most immunocompetent patients with herpes zoster who receive early treatment have a resolution of lesions within four weeks and can be managed outpatient.
As discussed in the history and physical section, a thorough examination of the HZO patient may reveal an array of complications, including blepharitis, conjunctivitis, keratitis, uveitis, and secondary glaucoma. Prolonged inflammation and corneal scarring can lead to serious complications, including permanent vision loss. Neurotrophic keratopathy, resulting from dysfunctional corneal innervation, leaves patients more susceptible to corneal abrasions, corneal ulcers, and persistent corneal epithelial defects, even in the absence of replicating virus or active inflammation. Necrotizing retinitis is an uncommon complication of HZO that can lead to retinal tears, retinal detachment, and subsequent permanent vision changes. Additionally, patients with HZO commonly develop postherpetic neuralgia (PHN) as a result of a peripheral nerve injury. PHN is a chronic painful condition in which herpes zoster pain persists for more than 90 days after the initial rash outbreak. Older age and severe disease are risk factors for PHN, while prior zoster vaccination appears to be protective. In addition to complications directly related to HZO, patients are also prone to secondary bacterial infections.
As part of their preventative care guidelines, the United States Centers for Disease Control and Prevention (CDC) recommends adults over 50-years-old receive herpes zoster vaccination to lower their risk of viral reactivation. There are currently two vaccines on the market - a live attenuated vaccine and an inactivated recombinant vaccine. The live vaccine first came on the market in 2006 and is administered as a one-time dose. It has about a 51% efficacy rate. As a live vaccine, it is contraindicated in immunocompromised patients. The inactivated vaccine was approved in 2018 and is administered as a 2-dose series. It has demonstrated a 97% efficacy in patients aged 50 to 70 and a 90% efficacy in patients older than 70 years. The CDC recommends the inactivated vaccine over the live vaccine due to its higher efficacy. Patients can still receive the inactivated vaccine despite having previously received the live vaccine. The safety of the inactivated vaccine in immunocompromised patients is still under investigation. While vaccination does not completely protect against herpes zoster, vaccinated individuals tend to have shorter and less severe disease courses. The spread of disease can be mitigated by advising all patients with an active infection to keep the rash covered and perform frequent handwashing. Those with disseminated disease also require airborne precautions. All patients with herpes zoster should avoid contact with pregnant women, immunologically naïve infants and children, and immunocompromised individuals.
HZO prevention and management involves an interprofessional approach. Preventative efforts often take place in the primary care office where patients receive education on vaccination. Patients with acute disease may present to their primary care provider, urgent care, or the emergency department. It is important that these first-contact providers initiate antiviral treatment and promptly consult and refer to ophthalmology for further evaluation. Pharmacists can assist with dosing regimens and provide information on pharmacodynamic interactions. Those with severe disease may require inpatient admission under the care of a hospitalist and a consulting ophthalmologist. Patients may go on to develop a prolonged disease course with chronic complications requiring frequent follow-up visits with their healthcare team.
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