Herpes Ophthalmicus

Aka: Herpes Ophthalmicus, Zoster Ophthalmicus, Herpes Zoster Ophthalmicus, Ophthalmic Herpes Zoster, Hutchinson's Sign

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II. Epidemiology

  1. Varicella Zoster Virus seropositivity: 95% U.S. adults
    1. Lifetime reactivation of VZV as Shingles: 50%
      1. Incidence Herpes Zoster Ophthalmicus: rare

III. Pathophysiology

  1. Initial: Varicella Zoster Virus Infection
  2. Dormancy: VZV lies dormant in Trigeminal NerveGanglion
  3. Reactivation: VZV reactivates in Trigeminal Nerve
  4. Ocular involvement is via the first 2 branches of the Trigeminal Nerve

IV. Predisposing Factors

  1. Immunocompromised Condition (decreased T-Cell Immunity)
    1. Advanced age
    2. Human Immunodeficiency Virus (HIV)
    3. Cancer
    4. Chemotherapy
    5. Radiation Therapy
  2. Acute Herpes Simplex Virus Infection
  3. Reactivating factors
    1. Local Trauma
    2. Fever
    3. Ultraviolet light
    4. Cold wind
    5. Systemic illness
    6. Menstruation
    7. Emotional stress

V. Symptoms

  1. Prodrome (precedes rash by several days)
    1. Lancinating pain lateral to affected eye
    2. Fever
    3. Malaise
    4. Headache
    5. Neck stiffness
  2. Dermatitis (see below)
    1. Ocular involvement may precede rash
  3. Eye Pain
  4. Lacrimation
  5. Visual changes
  6. Unilateral Red Eye

VI. Signs

  1. Hutchinson's Sign (1864)
    1. Nasociliary branch of V2 involvement (tip of nose)
    2. Heralds VZV ocular involvement (2 fold risk)
    3. Ocular effects occur despite no sign in 33% of cases
  2. Herpes Zoster type dermatitis
    1. Vesicular erythematous rash
    2. Follows first Trigeminal Nerve division
      1. Forehead
      2. Eyelid (Blepharitis)
      3. Cornea
    3. Crusts develop after the sixth day of the rash
  3. Lymphadenopathy
  4. Ocular exam
    1. Corneal staining
      1. Fluorescein staining: HSV
      2. Rose bengal staining: HSV and VZV
    2. Slit-lamp exam
    3. Intraocular Pressure
    4. Dilated Funduscopic Exam
  5. Ocular changes (changes develop within 3 weeks of rash)
    1. Iritis or Iridocyclitis
    2. Corneal Dysesthesia (or decreased Sensation)
    3. Punctate epithelial Keratitis
      1. Appear as soon as 1-2 days after rash
      2. May proceed to Dendrite formation
    4. Dentritiform Keratopathy on Fluorescein exam
      1. Branching with "hyphae-like" patterns
    5. Decreased Visual Acuity
    6. Conjunctivitis (Staphylococcus Aureus superinfects)
    7. Acute Retinal necrosis

VII. Differential Diagnosis

  1. Herpes Keratitis
    1. Herpes Keratitis crosses the midline whereas Herpes Zoster Ophthalmicus does not
  2. Conjunctivitis
  3. Corneal Abrasion
  4. Acute Narrow Angle Glaucoma
  5. Iritis
  6. Uveitis
  7. Scleritis
  8. Trigeminal Neuralgia
  9. Migraine Headache
  10. Meningitis

VIII. Labs

  1. Viral Culture from Cornea, Conjunctiva, or skin
  2. Giemsa stain from Cornea or skin scrapings
  3. Immunocompromised evaluation for age under 40 years

IX. Complication

  1. Stromal Keratitis
    1. Anterior stromal Keratitis (nummular Keratitis)
      1. Occurs during week 2 in 25% of cases
      2. Fine granular Corneal infiltrates deep to Dendrites
    2. Deep stromal Keratitis
      1. Uncommon, develops after anterior stromal Keratitis
      2. Develops 3-4 months after onset
      3. Involves central Cornea
  2. Neurotrophic Keratitis
    1. Pathophysiology
      1. Decreased Corneal Sensation
      2. Decreased Lacrimation
      3. Corneal thinning
    2. Results
      1. High risk of Traumatic Injury or perforation
      2. Risk of Bacterial superinfection
  3. Episcleritis or Scleritis
  4. Iritis
  5. Anterior Uveitis (common and usually mild)
    1. May be complicated by Glaucoma or Cataracts
  6. Ischemic Papillitis
  7. Orbital Vasculitis
  8. Ocular motor palsy
  9. Retinitis
    1. Acute Retinal necrosis
    2. Progressive outer Retinal necrosis
      1. Severe retinitis in Immunocompromised patients
  10. Visual Loss
  11. Postherpetic Neuralgia (occurs in 7% of cases)

X. Management: Acute

  1. Urgent Ophthalmology Consultation
  2. Antiviral Agents
    1. General
      1. Reduces ocular complications (Keratitis, Uveitis)
      2. Best prognosis when started early (within 72 hours)
      3. Efficacious if used as late as 7 days after onset
      4. Recovery rates and outcomes similar between IV and oral Antiviral Agents
        1. Pupic-Bakrac (2022) J Craniofac Surg 33(8): 263-7 [PubMed]
    2. Acyclovir oral or intravenous
      1. Dose: 800 mg PO five times daily for 7-10 days
      2. Intravenous dose for Immunocompromised patients
    3. Valacyclovir (Valtrex)
      1. Dose: 1000 mg PO tid for 7-14 days
    4. Famciclovir (Famvir)
      1. Dose: 500 mg PO tid for 7 days
  3. Anti-staphylococcal Antibiotics
    1. Augmentin
    2. Zithromax
  4. Prednisone
    1. Use only per Ophthalmology Consultation (risk of Corneal perforation)
  5. Inpatient admission criteria
    1. Severe symptoms or multiple Dermatomes involved
    2. Immunocompromised condition
    3. Significant facial Bacterial superinfection

XI. Management: General Measures

  1. Ocular Lubricants (e.g. Artificial Tears)
  2. Warm, moist compresses to affected eye
  3. Never use ocular Topical Anesthetics for home

XII. Management: Acute and Postherpetic Neuralgia

  1. Oral Narcotic Analgesics
  2. Capsaicin to involved skin only
  3. Amitriptyline (Elavil)

XIII. References

  1. Ritterband (1998) Rev Med Virol 8(4): 187-201 [PubMed]
  2. Karlin (1993) Ann Ophthalmol 25(6):208-15 [PubMed]
  3. Cobo (1988) Am J Med 85(2A):90-3 [PubMed]
  4. Pavan-Langston (1995) Neurology 45(12 Suppl 8):S50-1 [PubMed]
  5. Liesegang (1991) Ophthalmology 98(8):1216-29 [PubMed]
  6. Liesegang (1999) Cornea 18(5):511-31 [PubMed]
  7. Marsh (1993) Eye 7(Pt 3): 350-70 [PubMed]
  8. Shaikh (2002) Am Fam Physician 66(9):1723-32 [PubMed]

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