Herpes Zoster Ophthalmicus

Herpes zoster ophthalmicus (HZO) is reactivation of varicella zoster virus in the ophthalmic (first) division of the trigeminal nerve, causing a vesicular dermatomal rash and ocular inflammation. It makes up 10 to 20 percent of all zoster and affects about half of those with a first division rash if untreated.

• Lifetime risk of zoster is about 25 to 30 percent and rises with age (peak above 60 years), immunosuppression, HIV, malignancy, and transplantation.
• Involvement of the nasociliary branch (vesicles on the tip, side, or root of the nose, Hutchinson sign) predicts ocular involvement in roughly two thirds.
• Chronic or relapsing disease can persist for years because of persistent viral antigen and neuronal damage, causing progressive corneal and uveal disease.

• Prodrome of malaise, fever, and burning or tingling pain over the forehead, followed by a unilateral erythematous vesicular rash respecting the midline, crusting over 2 to 3 weeks and leaving scars.
• Ocular features may appear days to weeks after the rash:
  • Lids and conjunctiva: swelling, ptosis, follicular or papillary conjunctivitis.
  • Cornea: punctate epithelial keratitis, pseudodendrites (raised, non-terminal-bulb lesions), nummular infiltrates, stromal keratitis, disciform keratitis, neurotrophic keratopathy, and corneal scarring and melting.
  • Episcleritis, scleritis; anterior uveitis with raised intraocular pressure and iris atrophy (sectoral).
  • Posterior segment: acute retinal necrosis and progressive outer retinal necrosis (immunocompromised), optic neuritis, and retinal vasculitis.
  • Neurological: cranial nerve palsies (III, IV, VI), orbital apex syndrome, and vasculopathy with stroke (a delayed contralateral hemiparesis weeks to months after).
• Post-herpetic neuralgia (pain more than 90 days after rash onset) occurs in about 20 to 30 percent of older patients.

• Clinical, based on dermatomal rash; PCR of vesicle fluid, corneal scrape, or aqueous humour confirms atypical disease; serology for VZV IgG and IgM is of limited value.
• Slit lamp with fluorescein, corneal sensation testing (reduced), intraocular pressure measurement, and dilated fundus examination.
• Consider HIV testing and evaluation for malignancy in unexplained disease in younger patients.
• Neuroimaging (MRI with angiography) for neurological signs or stroke symptoms.
• Differential diagnosis: herpes simplex dermatitis and keratitis, contact dermatitis, impetigo, and cellulitis.

• Antiviral therapy within 72 hours of rash onset (still useful later in ocular disease):
  • Valaciclovir 1 g orally three times daily for 7 days, or aciclovir 800 mg orally five times daily for 7 to 10 days, or famciclovir 500 mg orally three times daily for 7 days. Adjust for renal function.
  • Intravenous aciclovir 10 mg/kg every 8 hours for 7 to 10 days for immunocompromised patients, retinal necrosis, encephalitis, or severe disease, with hydration to prevent crystal nephropathy.
• Ocular therapy:
  • Topical corticosteroid (prednisolone acetate 1 percent four to six times daily, tapered over months) for stromal keratitis, disciform keratitis, and anterior uveitis; steroids are avoided in pseudodendritic or epithelial disease until it heals.
  • Cycloplegia (cyclopentolate 1 percent twice daily) in uveitis; ocular lubricants preservative free; topical antibiotic ointment for the epithelial defect; bandage lens or tarsorrhaphy for neurotrophic disease; cenegermin for persistent neurotrophic ulcers.
  • Raised pressure: timolol 0.5 percent twice daily and acetazolamide 250 mg four times daily as needed (avoid prostaglandin analogues in active inflammation).
  • Scleritis and refractory disease: oral prednisolone 0.5 to 1 mg/kg with antiviral cover.
• Suppressive therapy for chronic or relapsing disease: valaciclovir 1 g once daily for up to 12 months reduces recurrence of keratitis and iritis. Adjust dose for renal function.
• Retinal necrosis: intravenous aciclovir followed by oral valaciclovir 2 g three times daily (or equivalent) for 6 to 12 weeks, intravitreal ganciclovir 2 mg or foscarnet 2.4 mg, and laser retinopexy to reduce detachment.
• Post-herpetic neuralgia: amitriptyline 10 to 25 mg at night, increasing as tolerated; gabapentin 300 mg at night titrated to 1800 to 3600 mg daily in divided doses; pregabalin 75 mg twice daily up to 150 mg twice daily; topical lidocaine 5 percent patches (up to 3 for 12 hours daily); capsaicin 8 percent patch; opioids as last choice.
• Acute pain: paracetamol 1 g every 6 hours, NSAIDs, and short course opioids as needed.
• Prevention: recombinant adjuvanted zoster vaccine, 2 doses 2 to 6 months apart, in adults aged 50 years and over and in immunocompromised adults aged 18 years and over, including after an episode; this reduces zoster risk by over 90 percent.
• Follow up: regular review for at least a year after the acute episode; patients need long term monitoring for corneal sensation, pressure, and uveitis.
• Complications: corneal scarring and neurotrophic ulceration, glaucoma, cataract, retinal necrosis and detachment, chronic pain, and stroke.