Ophthalmic Shingles

Synonyms: Herpes zoster ophthalmicus (HZO), ophthalmic herpes zoster

The human herpesvirus-3 (HHV3) causes chicken pox (varicella), usually in childhood. The virus then lays dormant in the sensory nervous system in the geniculate, trigeminal or dorsal root ganglia from whence it may flare up many decades later. If it affects the geniculate ganglion it can produces ophthalmic herpes, affecting the area covered by the ophthalmic division of the trigeminal nerve. It produces the Ramsey-Hunt syndrome if it affects the mandibular division. The maxillary division is rarely involved. There is not always a clear reason for a flare-up but associations include ageing, immunosuppressive illness, new stress or new medical treatments.¹

• This is a common problem: herpes zoster affects as many as 20% of people in the course of their lifetime and 10 to 20% of herpes zoster is ophthalmic (so one in 100 individuals will experience herpes zoster ophthalmicus).²
• The incidence is between 2.2 and 3.4/1000 people per year.
• Shingles tends to be a disease of old age (the incidence rises to about 10/1000 per year in the population over 80)² but it can strike much younger and is more severe in immunocompromised individuals.³
• The condition affects both sexes equally.

General points

• Old age is the commonest risk factor but it is also commoner in immunocompromised patients. If a patient presents with the condition below 50 years old there should be a search for a cause of immunocompromise.⁴
• There is often a prodromal phase of 2 or 3 days during which there is malaise (± low-grade fever) and either paraesthesia or pain over the affected area. The pain may be tingling, burning, stabbing or severe discomfort and occurs in about 60% of patients before the rash appears.¹ In ophthalmic shingles there may be photophobia too. The forehead is often tender.

Skin manifestations

• Most commonly, a rash develops that is first erythematous, then maculopapular, evolving into a vesicular rash.
• Shingles almost invariably is unilateral and affects just one dermatome (although it is not uncommon to find that not all the dermatome is affected). If more than one dermatome is involved or it crosses the midline either alternative diagnoses should be considered, or the patient may be immunocompromised.
• In the immunocompetent a few satellite lesions may appear just outside the area of the dermatome and occasionally two adjacent dermatomes may be affected. The ophthalmic division of the V cranial nerve goes from below the eyes up to the crown of the head but the forehead, around the eye and on to the nose is the commonest area to be involved.
• The vesicles develop into crusts by about the 5th or 6th day.
• If there is no rash it is called herpes zoster sine herpete.

Ocular manifestations

• The eye is affected in only about half of cases (the likelihood of this occurring is not related to age or the severity of the rash)² but this is a justly feared complication of this condition. If the tip of the nose has a rash, the nasociliary branch of the trigeminal nerve is involved. This branch supplies the globe and so it is very likely that the eye will be affected (at least 75% of cases). This is called Hutchinson's sign as he described it in 1868. The eye can be seriously affected with little evidence of a shingles rash. If Hutchinson's sign is seen it is wise to refer to an ophthalmologist immediately rather than waiting for the inevitable development of eye complaints.
• Acute lesions of the orbit or globe develop within three weeks of the onset of the rash. They may resolve swiftly or linger and recur over years.
• Symptoms include pain in the eye, redness, impaired vision and tears rolling down the face.
• Shingles is often thought of as a sensory problem except in the Ramsey-Hunt syndrome when the face drop resembles Bell's palsy. However, it does cause some motor impairment too. There may be loss of corneal sensation and reduction in the blink reflex so that the eye is at risk. Poor muscle tone accounts for the tears but the eye may be dry and vulnerable from lack of tears.
• Other problems affect various parts of the eye:
  • Lids - bilateral eyelid oedema can develop, giving the erroneous impression of a bilateral problem³ as well as blepharitis and ptosis⁵
  • Conjunctiva - giving rise to a follicular conjunctivitis
  • Episclera and sclera - resulting in inflammation (episcleritis and scleritis)
  • Cornea - multiple features may occur e.g. multiple small epithelial dendrites, stromal and neurotrophic keratitis, raised mucous plaques etc - this is one of the sites where significant visual loss can occur⁵
  • Anterior part of the eye - uveitis, paralysis ± atrophy of the iris and secondary glaucoma (about 10% of cases)⁶
  • Posterior part of the eye - retinitis, choroiditis and optic neuritis

The diagnosis is usually clinical, based on typical lesions in a single dermatome. Various techniques to detect the virus or antibody detection may be possible after consultation with a microbiologist. Tzanck smears may yield results but scraping for smears and cultures are usually negative.

• Cluster headaches or migraine - consider in the prodromal phase.
• Herpes simplex infection - the rash, which tends to occur in younger patients, does not particularly follow a dermatome or stop at the midline.
• Consider the differentials of the acute red eye where there is no rash (e.g. conjunctivitis, corneal abrasion, keratitis). If you strongly suspect HZO, look for a rash or evidence of a previous rash such as pigmentary changes along the hairline or consider zoster sine herpete.

The risk to the eyesight from ophthalmic herpes is such that all patients suspected of having the condition should be seen by an ophthalmologist. Referral should ideally be within 24 hours (certainly within a few days)² but initiation of antiviral therapy should be immediate.

Oral antiviral therapy

• Oral antiviral therapy should be started within 72 hours of the onset of the rash. If it is started any later it is much less effective and there is a greater risk of post herpetic neuralgia.
• The drugs that are used are aciclovir 800 mg five times a day, valaciclovir 1000 mg three times a day and famciclovir 500 mg three times a day. (The effectiveness of the second generation antivirals in reducing eye complications is less well studied than with aciclovir but patients may be more likely to comply with the treatment regime).²
• All are given for 7 days although longer treatments may be required in the elderly and the immunocompromised.¹
• It is recommended that oral antivirals should still be given if the patient presents after 72 hours ophthalmic shingles, Ramsey-Hunt syndrome, the elderly and the immunosuppressed. The patient may fall into more than one of these four categories.
• Early and effective treatment reduces complications.⁷

Topical treatment

Although some advocate the use of topical treatment (aciclovir or penciclovir cream and a steroid-antibiotic combination e.g. Fucidin-H, tds), evidence suggests treatment is inadequate compared with oral therapy and adds no further benefit.⁸ As a secondary bacterial conjunctivitis is a risk a better case can be made for antibiotic eyedrops. Topical steroids are inferior to topical aciclovir.⁹ Warm compresses to the skin may help relieve discomfort.

Treatment of ocular problems

Where there is intraocular involvement, various agents are used depending on which tissue is involved. Patients may benefit from long term application of ocular lubricants and cool compresses are advised for the conjunctivitis in the acute phase. Topical steroids may be started under ophthalmic supervision only (these are beneficial in certain specific cases and harmful in others). Treatment may go on for many months or even years. Patients may also require cycloplegics to help pain relief and intraocular pressure lowering drugs. Where there is retinitis, choroiditis or optic neuritis, the patient may need admission for intravenous antivirals.^6,5

Analgesia

It may be necessary to give quite strong analgesia for the pain. If the pain is severe beyond the moment that the vesicles have crusted over, post-herpetic neuralgia has probably developed.¹ Do not treat corneal pain with topical anaesthetics - these are toxic to the cornea.

Most (immunocompetent) patients will completely recover within a few weeks.² However, some do go on to develop the complications outlined below. These are not related to age or the extent of the rash but they do seem to be more severe in the immunocompromised host. They can occur months or years after the initial attack.²

• Ocular complications occur in 50% of cases. Of these, pain occurs in 93% of these patients and is still present at 6 months in 31%. Of those affected, anterior uveitis occurs in 92% and varieties of keratitis in 52%. At 6 months, 28% of involved eyes have long-term disease, with chronic uveitis, keratitis, and neuropathic ulceration being the commonest.¹¹
• Rare ocular complications include optic neuritis, retinitis and ocular cranial-nerve palsies. Sight is threatened by neuropathic keratitis, perforation, secondary glaucoma, posterior scleritis, optic neuritis, and acute retinal necrosis.
• Long term complications may be related to poor sensation of the cornea and poor motor function of the eyelid. This may put the eye at risk during episodes of impaired consciousness. There is risk of neuropathic ulceration and exposure keratopathy. There is also a risk of complications common to the disease elsewhere, like post herpetic neuralgia. The risk of long term problems is such that it is recommended that a history of ophthalmic herpes zoster should remain in the problems section of the medical record. There is a 6 to 14% chance of recurrence.²
• Permanent sequelae of ophthalmic zoster infection may include chronic ocular inflammation, loss of vision, and debilitating pain.⁵ Gradual clouding of the cornea may occur.