Timely detection of herpes zoster ophthalmicus is key

Shingles or herpes zoster is a common clinical presentation among older adults aged 60 and above.^1,2 It results from reactivation of the varicella zoster virus, which is responsible for the common childhood disease, chickenpox. Following the primary chickenpox infection, the virus persists in dorsal ganglion cells of the adult nervous system before reactivating later in life as herpes zoster.³ As a result, painful vesicular rashes typically manifest along the involved dermatome.⁴

When the ophthalmic division (V1) of the trigeminal nerve along the face is involved during reactivation (Figures 1 and 2), this is called herpes zoster ophthalmicus.⁵ HZO accounts for 10–20 per cent of herpes zoster cases.⁶

The nasociliary nerve derives from the V1 division of the trigeminal nerve and innervates the anterior and posterior ethmoidal sinuses, skin of the eyelids and tip of the nose, conjunctiva, sclera, cornea, iris and the choroid. Vesicular rash involving the tip, side or root of the nose is associated with a higher rate of ocular involvement and is termed Hutchinson sign. Conjunctivitis, uveitis (iritis) and keratitis are the most common ocular manifestations of HZO.^4,5

Prodromal symptoms of HZO may include fever, malaise, nausea and headache.⁵ Most patients with acute herpes zoster of the head experience pain prior to eruption of vesicles. Typically, the pain is of a stabbing quality, unilateral, moderate to severe and often wakes patients from sleep.⁷ Importantly, HZO must be considered by primary care physicians among older patients with V1 hyperalgesia not responding to simple analgesia, even in the absence of vesicular rash as the pain may sometimes precede the rash by several days.

Conjunctivitis appears to be the most common ocular complication of HZO, followed by keratitis (Figure 3) and anterior uveitis (Figure 4).^4,8 Corneal scar, neurotrophic keratopathy, band keratopathy, corneal melt, corneal perforation and acute retinal necrosis or panuveitis are further complications of HZO that also contribute to vision loss.⁸

Vision loss (reduction in the best-corrected visual acuity by at least one line) has been reported in 12.4 per cent of patients after resolution of HZO.⁴ Permanent moderate vision loss (≤20/50) due to HZO was reported in 9.6 per cent of patients, and severe vision loss (≤20/200) in 3.6 per cent of patients, following an acute episode of HZO.⁸

Risk factors associated with vision loss include poor presenting visual acuity, older age, uveitis, immunosuppression and the number of HZO ocular manifestations. Older age is linked with uveitis and corneal involvement, which are also associated with vision loss after HZO.^4,8

Prevention of corneal scarring from corneal involvement in HZO seems to be an important target for preventing vision loss. Patients with uveitis or keratitis often require prolonged topical corticosteroid for at least three months, and recurrence rates on corticosteroid cessation remain high.

Anterior uveitis is a common ocular complication of HZO that results in blurred vision and intense photophobia.⁴ It is marked by ciliary injection, as well as inflammatory cells and proteinaceous flare in the anterior chamber, and keratic precipitates on the cornea.^9,10

Anterior uveitis usually develops within seven to 14 days of rash onset, and topical corticosteroid is required to control the anterior segment inflammation.^8,9 Therefore, it is ideal to refer patients with HZO to an ophthalmologist seven to 14 days after onset of rash for consideration of topical corticosteroid therapy.

Earlier review is advised when there is blurring of vision or photophobia. Conjunctivitis or eyelid involvement alone does not necessitate early ophthalmology review.

Cranial nerve palsy and cerebrovascular accident, also known as stroke, are rare but important complications of HZO.

Cranial nerve palsy was reported in 3.5 per cent of patients in one study group, with cranial nerve III involvement being the most common, followed by cranial nerve VI.⁸ Double vision may result when patients experience external ocular motor palsies, but fortunately, most appear to be transient during acute HZO, resolving over a period of approximately three months.⁵

HZO has been reported to increase the risk of CVA when compared with herpes zoster of other locations. While the incidence of CVA 12 months following HZO was rare (1.6 per cent), the risk was highest immediately following HZO, with median time to CVA of 2.3 months. Interestingly, it was found that patients who received prompt antiviral therapy had a 76.2 per cent lower hazard of CVA.¹¹

Current literature reports that the increased risk of CVA following HZO is most pronounced in individuals younger than age 40.^4,11 Promoting prompt antiviral commencement and vaccination against herpes zoster is crucial in reducing its associated ocular and cerebrovascular burden. Vaccination has been observed to decrease the risk of CVA in older adults.

Prompt commencement of antiviral therapy is key in optimal management of HZO.^5,9 The administration of an antiviral agent within 72 hours of rash onset has been shown to reduce acute HZO pain as well reduce the frequency and severity of ocular complications, including anterior uveitis.^10,12

Valacyclovir 1000mg can be prescribed three times daily for 10 days. Another option is to prescribe acyclovir 800mg five times daily. Antiviral dosage may need to be renally adjusted, so it is ideal to monitor renal function.⁹

An age-related decline in immunity is thought to contribute to greater risk for herpes zoster among adults aged 50 and over. Vaccination offers the best protection from shingles and its associated complications.^13,14

The Shingrix vaccine is a recombinant vaccine consisting of a varicella zoster virus glycoprotein and an adjuvant system that stimulates the immune response. The glycoprotein chosen is the most abundant viral surface glycoprotein in both varicella zoster virions and infected cells, and the adjuvant system comprises two immunostimulants.¹⁵

Two phase III trials evaluated the efficacy of Shingrix against herpes zoster in those aged 50 or older (ZOE-50 trial) and in those aged 70 or older (ZOE-70 trial). The overall vaccine efficacy was 97.2 per cent among those aged 50 or older, and 91.3 per cent among those aged 70 or older.^16,17

Shingrix is the shingles vaccine used in New Zealand and requires two doses to be administered two to six months apart. The vaccine is approved and recommended for those aged 50 or older, and those aged 18 or older at increased risk of herpes zoster.

However, only adults aged 65 are eligible for a free first dose of Shingrix vaccine, and the first dose must be administered within 12 months of turning 65 to be eligible for a free second dose. From 1 July, it will also be funded for some immunocompromised people aged 18 or older. Shingrix is readily available in New Zealand but can cost $600–$800 for those who are not eligible for free vaccination.^13,14

Vince Wilkinson is a fellow in ophthalmology at the University of Auckland. Rachael Niederer is an ophthalmologist and uveitis and medical retina specialist at Auckland Eye and Greenlane Clinical Centre, and a senior lecturer at the University of Auckland