Herpes Zoster Ophthalmicus (HZO)

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Aetiology

Herpes zoster ophthalmicus (HZO) is caused by a localized reactivation of the varicella zoster virus (VZV) in the ophthalmic division of the trigeminal nerve. VZV is also known as human herpesvirus-3 (HHV-3). The features of herpes zoster in general are:

  • previous systemic infection (varicella, i.e. chickenpox)
  • virus lies dormant (sometimes for decades) in dorsal root and cranial nerve sensory ganglia
  • reactivation leads to herpes zoster (shingles)
  • herpes zoster ophthalmicus (HZO) is defined by zoster involvement in the ophthalmic division of the trigeminal nerve
  • herpes zoster affects 20-30% of the population at some point in their lifetime; 10-20% of these will develop HZO through involvement of the ophthalmic division of the trigeminal nerve. This represents a lifetime incidence of one in 100 individuals
  • most cases of ocular involvement develop within three to four weeks of the intial primary care diagnosis
  • vaccination: some countries (e.g. USA, Canada, Australia, Japan, Germany) have a policy of vaccinating children against varicella. There is evidence that this is protective not only against chickenpox but also against herpes zoster in later life. In the UK, such vaccination is offered only to children who are particularly vulnerable to chickenpox, e.g. those undergoing chemotherapy
    • Public Health England introduced routine herpes zoster vaccination (with live vaccine, Zostavox) for people aged 70 years in 2013. This has been shown to reduce the incidence rate of shingles and post-herpetic neuralgia
    • In the USA, non-live vaccine (Shingrix) is regarded as superior in efficacy and long-term persistence and is offered to people aged 50 and over, regardless of whether they have previously received the live vaccine (which is no longer available in the USA). The non-live vaccine is not yet licensed for use in the UK.

Predisposing factors

Age: the peak incidence in healthy individuals is in the 5th to 7th decades, but one in three cases occur in people under the age of 50
Immune compromise: HIV/AIDS, medical immunosuppression

Symptoms of herpes zoster ophthalmicus

Pain and altered sensation of the forehead on one side
Rash affecting forehead and upper eyelid appears a day to a week later
General malaise, headache, fever
Ocular symptoms in acute phase

  • discomfort
  • discharge
  • redness
  • pain
  • photophobia

Signs of herpes zoster ophthalmicus

Skin features

  • unilateral painful, red, vesicular rash on the forehead and upper eyelid, progressing to crusting after 2-3 weeks; resolution often involves scarring
  • periorbital oedema (may close the eyelids and spread to opposite side)
  • lymphadenopathy (swollen regional lymph nodes)
  • lesion at the side of the tip of the nose (Hutchinson’s sign) indicates three times the usual risk of ocular complications, but these may also occur in one in three patients without the sign

Ocular lesions (variable in scope and severity, may be chronic or recurrent):

  • mucopurulent conjunctivitis (common), associated with vesicles on the lid margin; usually resolves within 1 week
  • keratitis (more than half of all cases)
    • punctate epithelial – early sign, within 2 days (50% of cases)
    • pseudodendrites – fine, multiple stellate lesions (around 4-6 days)
    • nummular – fine granular deposits under Bowman’s layer
    • disciform – 3 weeks after the rash (occurs in 5% of cases)
    • reduced corneal sensation (neurotrophic keratitis)
    • endothelial changes and KP
  • episcleritis: occurs in around one third of cases
  • scleritis: less common; usually develops after 1 week
  • anterior uveitis
  • secondary glaucoma
  • rarely, posterior segment involvement: retinitis, acute retinal necrosis, choroiditis, optic neuritis, optic atrophy
  • rarely, neurological complications: cranial nerve palsies, encephalitis
  • post-herpetic neuralgia is defined as pain and/or itch lasting beyond 90 days after the onset of zoster. This affects around 25% of patients and is chronic and severe in about 7%

Complications can occur months or years after the acute phase

Differential diagnosis

Ocular lesions: herpes simplex keratitis
Cutaneous lesions: cellulitis, contact dermatitis, atopic eczema, impetigo

Management by optometrist

Practitioners should recognise their limitations and where necessary seek further advice or refer the patient elsewhere

Non pharmacological

Exclude uveitis and posterior segment complications, e.g. retinal necrosis (dilated fundus examination required)
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Advise rest and general supportive measures (reassurance, support at home, good diet, plenty of fluids)
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Advise avoidance of contact with elderly or pregnant individuals, also babies and children not previously exposed to VZV (who are non-immune) or immunodeficient patients
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Pharmacological

Topical lubricants for relief of ocular symptoms
Pain relief: aspirin, paracetamol or ibuprofen (check history for contraindications). Stronger analgesics (e.g. opiates) may be indicated (co-manage with GP)
(GRADE*: Level of evidence=low, Strength of recommendation=strong)
 

Management category

A1: for acute skin lesions: emergency referral (same day) to GP for systemic anti-viral treatment
Early treatment with oral aciclovir (within 72 hours after rash onset) reduces the percentage of eye disorders in ophthalmic zoster patients from 50% to 20-30%. This early treatment also lessens acute pain.

(NB this recommendation, though representing conventional practice, is currently not evidence based. The on-going Zoster Eye Disease Study [ZEDS], due to complete at the end of July 2021, may resolve this matter)

A3: first aid measures and urgent referral (within one week) to ophthalmologist if:

  • deeper cornea involved
    • untreated disciform keratitis can lead to scarring
    • neurotrophic ulceration can lead to perforation
  • anterior uveitis present
  • IOP raised

B3: management to resolution if co-managed with GP and keratitis mild and limited to epithelium
Requires careful monitoring. Maintain low threshold for referral since HZO is associated with chronic and recurrent complications that may be sight threatening

Possible management by ophthalmologist

Systemic anti-virals e.g. aciclovir, famciclovir, valaciclovir
Topical anti-virals (off-licence use)
Topical steroids
Immunosuppressive therapy for scleritis
Botulinum toxin-induced ptosis or surgical tarsorrhaphy for neurotrophic corneal ulceration
Treat other ocular complications

Evidence base

*GRADE: Grading of Recommendations Assessment, Development and Evaluation (www.gradingworkinggroup.org)

Sources of evidence

Chen N, Li Q, Yang J, Zhou M, Zhou D, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2014;2:CD006866

Civen R et al. The incidence and clinical characteristics of herpes zoster among children and adolescents after implementation of varicella vaccination. Ped Infect Dis J 2009;28:954-9

Cohen EJ. Management and prevention of herpes zoster ocular disease. Cornea. 2015;34 Suppl 10:S3-8

Davis AR, Sheppard J. Herpes Zoster Ophthalmicus Review and Prevention. Eye Contact Lens. 2019 ;45(5):286-291.

Gelb LD. Preventing herpes zoster through vaccination. Ophthalmology. 2008;115(2 Suppl):S35-8

Li JY. Herpes zoster ophthalmicus: acute keratitis. Curr Opin Ophthalmol. 2018;29(4):328-333

McDonald EM, de Kock J, Ram FS. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. Antivir Ther. 2012;17(2):255-64

Opstelten W, Zaal M. Managing ophthalmic herpes zoster in primary care. BMJ 2005;331:147–51

Ting DSJ, Ghosh N, Ghosh S. Herpes zoster ophthalmicus. BMJ. 2019;364;k5234

Vadoothker S, Jeng BH. Management of chronic complications associated with herpes zoster ophthalmicus. Curr Opin Ophthalmol. 2018;29(4):334

Plain language summary

Herpes Zoster Ophthalmicus (HZO) is a viral infection of the nerve that supplies sensation (touch and pain) to the eye surface, eyelids, forehead and nose (trigeminal nerve). The virus that affects it (Varicella Zoster Virus [VZV]) also causes chickenpox. Patients who develop HZO, like most people, have usually been exposed to chickenpox by the age of 16 and though they recover from that infection, the virus lies dormant in parts of the brain and spinal cord, with its activity suppressed by the body’s immune system. If, for some reason, that suppression weakens, viruses can become reactivated and travel down the trigeminal nerve, reaching the tissues that it supplies and causing inflammation. When the skin is involved, the condition is known as shingles. Shingles occurs more often and is likely to be more severe in older people whose immunity to VZV is weakening, and in people whose immune system is not functioning normally, as for example in HIV/AIDS, or is suppressed by medical treatment.

In HZO the skin of one side of the forehead and scalp is affected, along with the eye on the same side. Any part of the eye can be involved, but most commonly it is the eye surface, including the conjunctiva (the white of the eye) and the cornea (the clear window of the eye). The cornea reacts in various ways; the most serious long-term effects result from damage to the corneal nerves, causing loss of sensation.

When HZO first appears, patients benefit from anti-viral tablets prescribed as soon as possible, usually by the GP. Mild cases can be co-managed by the optometrist and the GP but more severe
cases need to be referred to the ophthalmologist.

Public Health England has introduced shingles vaccination for certain people aged between 70 and 80. This is given once and provides a good measure of protection against the condition.

Herpes Zoster Ophthalmicus (HZO)
Version 15
Date of search 21.02.21
Date of revision 30.07.21
Date of publication 01.10.21
Date for review 20.02.23
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