Herpes Zoster Ophthalmicus

VZV  distributions of the fifth cranial nerve (trigeminal nerve), shared by the eye and ocular adnexa

Red Flags

• Increased ocular involvement if rash involves the tip of the nose (Hutchinson’s sign).
• Early presentation with pain prior to rash onset.
• Delayed ocular involvement can occur up to 3 weeks post-rash.
• Isolate patient in a single room when diagnosis is first considered.
• Infectious precautions needed until skin lesions heal.
• Avoid exposure to non-immunised, previously unexposed (to chickenpox), and pregnant individuals.
• Disseminated zoster can occur in immunodeficiency, malignancy, and can rarely cause meningoencephalitis.

Background

• Incidence and severity increase with age, especially >60 years.
• Without antiviral therapy, ~50% of HZO patients develop ocular involvement.
• Rare occurrence of herpes zoster in previously vaccinated individuals.

Risk Factors

• age of 60 at the highest risk
•  immunosuppressive drugs  
• immunocompromised patient 

History

• Systemic: Prodromal symptoms (headache, fever, malaise), skin rash, dermatomal pain, paraesthesias.
• Ocular: Pain, redness, watering, photophobia, blurred/decreased vision.

Examination

• Complete ophthalmic examination including intraocular pressure (IOP), iris atrophy check, dilated retinal and cranial nerve exam.

Signs

• Erythematous skin lesions with macules, papules, vesicles, pustules, and crusting lesions in the distribution of the trigeminal nerve. 

Specific Examination Components

1. Skin
   • Appearance: Acute vesicular dermatomal rash in the V1 distribution, unilateral, respecting the midline.
   • Risk Indicator: Nasociliary involvement (Hutchinson’s sign) increases the risk of ocular involvement.
   • Hutchinson’s sign
     • skin lesions at the tip, side, or root of the nose. 
     • a strong predictor of ocular inflammation and corneal denervation in HZO
2. Eyelid/Conjunctiva (1-2 weeks post-rash onset)
   • Signs:
     • Vesicles on the skin, lid margin, or bulbar conjunctiva.
     • Blepharitis.
     • Unilateral conjunctivitis, often with petechial hemorrhages.
     • Periorbital edema.
     • Lid malposition, scarring, and trichiasis (late complications).
   • Decreased Visual Acuity
   • Acute Retinal necrosis
   • high intraocular pressure.
   • Visual Loss
3. Episclera/Sclera (1 week post-rash onset)
   • Signs:
     • Episcleritis.
     • Scleritis.
4. Cornea
   • Epithelial Disease:
     • Superficial Punctate Keratitis (SPK) (2-7 days): Initial manifestation, can progress to pseudodendrites.
     • Pseudodendrites (4-6 days): Elevated ‘stuck on’ plaques with a branching pattern and tapered ends (distinct from HSV dendrites which have terminal bulbs and stromal ulceration).
     • Corneal staining
       • Fluorescein staining: HSV
       • Dentritiform Keratopathy on Fluorescein exa
5. Stromal Disease:
   • Anterior Stromal Keratitis (1-2 weeks): Multiple fine granular infiltrates beneath pre-existing dendrites or SPK, nummular (coin-shaped) lesions.
   • Deep Stromal Keratitis (1 month – years): Stromal inflammation/infiltrates, corneal edema, associated uveitis.
   • Neurotrophic Keratopathy (1 month – years): Reduced corneal sensation, exposure epitheliopathy, corneal thinning with a risk of perforation, secondary bacterial infection.
6. Anterior Chamber
   • Anterior Uveitis (2 weeks – years): Often isolated or associated with keratitis, causes elevation in IOP at presentation, late iris atrophy, and an irregular pupil.
   • Trabeculitis: Associated with high IOP.
7. Posterior Segment
   • Acute Retinal Necrosis (ARN): Peripheral patches of retinitis that rapidly coalesce, occlusive vasculitis, vitreous inflammation, retinal detachment common.
   • Progressive Outer Retinal Necrosis (PORN): Risk in immunocompromised patients.
8. Other Complications
   • Lymphadenopathy
   • Cranial Nerve Palsies: VII, III (most common), IV, and VI nerve palsies occur rarely.
   • Orbital Inflammation/Myositis.
   • Optic Neuritis: Rare.
   • Post-Herpetic Neuralgia (PHN): Dermatomal pain persisting >3 months after rash, allodynia, reduced sensation, paraesthesia.

Differential diagnosis

• Not many disease processes produce a painful vesicular rash. 
• However, other conditions that create vesicular rashes should be considered especially in the absence of pain

Management of Herpes Zoster Ophthalmicus (HZO)

Skin Rash Treatment

• Objective: Prevent bacterial superinfection.
• Measures:
  • Keep lesions clean and dry.
  • Symptomatic relief with warm, moist compresses to the affected eye.
  • Apply chloramphenicol ophthalmic ointment TDS to lid vesicles to prevent secondary bacterial infection.

Ocular Treatment

• Lubricants: Use artificial tears or ointment for conjunctivitis, superficial punctate keratitis (SPK), pseudodendrites, and neurotrophic keratitis.
• Topical Steroids:
  • For stromal keratitis and uveitis.
  • Options: Fluorometholone (Flarex®), Prednisolone acetate 1%/phenylephrine (Prednefrin Forte®).
  • Selection and dosage depend on the severity of the disease.
  • Slow taper guided by clinical progress, noting that uveitis may require prolonged treatment.

Antiviral Therapy

• Oral Antivirals (preferably within 72 hours of rash onset, or within 7 days if there are active vesicles or in debilitated/immunocompromised patients):
  • Acyclovir: 800 mg PO five times daily for 7 to 10 days.
  • Famciclovir: 500 mg PO TID for 7 days.
  • Valacyclovir: 1000 mg PO TID for 7 days.

Systemic/Oral Prednisolone

• Indicated for episodes of scleritis, retinitis, choroiditis, and optic neuritis.
• Dosage and duration based on clinical severity and response.

Elevated Intraocular Pressure (IOP)

• Aqueous Suppressants: Timolol, brimonidine, dorzolamide, acetazolamide as needed.
• Management Considerations:
  • Treatment guided by the aetiology and severity of elevated IOP.
  • Increase frequency of topical steroids if uveitis is present.
  • Avoid concurrent use of prostaglandin analogues due to potential pro-inflammatory effects (controversial).

Pain Management

• General Pain:
  • Over-the-counter analgesics as first-line treatment.
  • Narcotics may be required for severe pain.
• Neuropathic Pain:
  • Amitriptyline 10 to 25 mg PO at night.
  • Pregabalin 150 mg/day BID.
  • Capsaicin cream applied to the rash.

Medical Follow-Up

• Acute Phase:
  • Monitor every 1 to 7 days during the acute episode based on ocular findings and severity.
• Post-Acute Phase:
  • Follow-up every 3 to 12 months to monitor for delayed sequelae such as ocular hypertension, cataract, and corneal scarring.
• Viral Prophylaxis:
  • Consider acyclovir 400 mg PO BID for prophylaxis if there is concern about future exacerbations.

Special Considerations

• Disseminated Zoster:
  • Occurs in immunodeficiency, malignancy, and can rarely cause meningoencephalitis.
  • Requires systemic antiviral treatment and close monitoring.
• ENT Referral:
  • Necessary for Herpes zoster oticus/Ramsey Hunt syndrome with otalgia, vesicular rash, vertigo, hearing loss, hyperacusis, or tinnitus.

Vaccine

• Zostavax®: Reduces incidence of herpes zoster and PHN, free for people aged 70-79 years in Australia.
• Not indicated during acute disease.
• Caution in vaccinating after HZO with ocular involvement.
• Suggested to wait at least one year post-episode before vaccination.

Surgery

• Cornea transplantation is sometimes required for lesions that cause severe cornea thinning and loss of structural integrity of the eye. 
• Scars that are visually significant and refractory to medical therapy and/or hard contact lenses may require transplantation.
• Vitrectomy/Retina detachment surgery may be performed especially in cases of acute retinal necrosis (ARN). Glaucoma filtration surgery is sometimes performed if there are difficulties with maintaining optimum intraocular pressure