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BASICS

Description

  • Eye infections caused by herpes simplex virus (HSV) types 1 or 2 and varicella-zoster virus (VZV/HHV3).
  • HSV primarily causes keratoconjunctivitis; VZV causes herpes zoster ophthalmicus (HZO) on reactivation.
  • Involves eye, skin, CNS (notably neonatal HSV).

Epidemiology

  • HSV: Mean onset ~37 years; can affect all ages including neonates.
  • VZV: Typically >50 years; ~1 million shingles cases/year in US; 25-40% have ophthalmic involvement.
  • HZO lifetime prevalence ~1%.

Etiology and Pathophysiology

  • HSV: Transmission via saliva, genital contact, birth canal.
  • Primary infection can cause severe neonatal disease.
  • VZV: Primary infection causes chickenpox; virus latency in trigeminal ganglia; reactivation causes shingles and HZO.
  • Reactivation triggers: stress, trauma, UV exposure, immunosuppression.

Risk Factors

  • HSV: History of infection or close contact, UV exposure, immunosuppression.
  • VZV: Prior varicella infection, age >50, female sex, immunosuppression.
  • Consider immunodeficiency in zoster patients <40 years.

Prevention

  • Contact precautions for active lesions.
  • VZV recombinant vaccine (Shingrix) recommended for ≥50 years.
  • Avoid varicella vaccine during acute infection.
  • Acyclovir prophylaxis to prevent HSV ocular recurrence.
  • Pregnant women avoid contact with active zoster cases; Shingrix contraindicated in pregnancy.

DIAGNOSIS

History

  • Variable presentation depending on virus and eye structure affected.
  • HSV: recurrent keratitis, eye pain, redness, photophobia, blurred vision.
  • VZV/HZO: prodrome of fever, malaise, eye pain followed by unilateral dermatomal vesicular rash.

Physical Exam

  • Usually unilateral.
  • HSV: affects corneal epithelium.
  • VZV: affects corneal stroma and uvea.
  • Signs: decreased visual acuity, conjunctival injection near limbus, decreased corneal sensation, dendritic lesions on fluorescein stain.
  • Hutchinson sign (vesicles on nose) predicts higher risk of HZO.

Differential Diagnosis

  • Other causes of red, painful eye: bacterial/fungal conjunctivitis, acute glaucoma, corneal abrasion, temporal arteritis.

Diagnostic Tests

  • Mainly clinical diagnosis.
  • Corneal swab PCR for HSV DNA (PPV 96%).
  • Tzanck smear for multinucleated giant cells if vesicles present.
  • Urgent ophthalmology referral for slit-lamp, fundus exam, intraocular pressure.

TREATMENT

General Measures

  • Avoid contact with nonimmune individuals.
  • No contact lens use during treatment.
  • Supportive: cool compresses, artificial tears, analgesics.

Medications

First Line

  • HSV epithelial keratitis:
  • Topical trifluridine 1% eye drops q2h awake (max 9 drops/day), then taper.
  • Oral acyclovir 400 mg PO 5x/day for 10 days.
  • Ganciclovir 0.15% gel q3h awake alternative.
  • Avoid topical steroids in epithelial disease.
  • Ophthalmologic epithelial debridement may accelerate healing.
  • HSV stromal keratitis or uveitis:
  • Combination antiviral + topical steroids (prednisolone acetate 1% QID, slow taper).
  • Consider systemic steroids for severe uveitis.
  • HZO:
  • Oral valacyclovir 1 g TID × 7–10 days or famciclovir 500 mg TID or acyclovir 800 mg 5x/day.
  • Valacyclovir and famciclovir reduce postherpetic neuralgia (NNT = 3).
  • Topical antibiotic ointment (bacitracin, polymyxin B) to protect ocular surfaces.
  • IV acyclovir 10–15 mg/kg q8h for immunocompromised.
  • Topical steroids with ophthalmologist guidance.
  • Cycloplegics if anterior uveitis present.

Second Line

  • HSV intolerant to topical antivirals: oral acyclovir 2 g/day divided doses.
  • Other antivirals (idoxuridine, brivudine) not US-approved.
  • Interferon: not currently available.

Alerts

  • Initiate antiviral therapy within 72 hours of HZO rash onset; can be started later due to possible benefit.
  • Prolonged topical antiviral use (>10–14 days) toxic to corneal epithelium.
  • Topical steroids contraindicated in active epithelial disease; require ophthalmologist supervision.

ISSUES FOR REFERRAL

  • Emergent or urgent ophthalmology referral depending on severity.
  • Neonatal HSV requires specialized care.

ADDITIONAL THERAPIES

  • Recurrent HSV: suppressive antiviral therapy.
  • Postherpetic neuralgia: gabapentin, pregabalin, TCAs, opioids, lidocaine gel.

SURGERY/OTHER PROCEDURES

  • Corneal transplantation for severe scarring or perforation.

ONGOING CARE

Follow-Up Recommendations

  • Slit-lamp exam every 1–2 days until improvement, then every 3–4 days until epithelial defect resolves.
  • Weekly monitoring after antiviral discontinuation until stable.

Patient Education

  • Early recognition of recurrence important.
  • Prompt evaluation and treatment reduces risk of complications.

PROGNOSIS

  • Many cases self-limited.
  • HSV ocular infection is leading cause of infectious blindness worldwide.
  • Untreated HSV epithelial disease resolves in 40% without sequelae; with treatment 90–95% resolve without complications.
  • Neonatal HSV has high morbidity and mortality.
  • VZV PHN occurs in 20–40%, longer lasting in older adults.

COMPLICATIONS

  • Recurrence.
  • Corneal neovascularization and scarring.
  • Neurotrophic ulcer and perforation.
  • Secondary infections (bacterial/fungal).
  • Secondary glaucoma (~10%).
  • Vision loss from optic neuritis or chorioretinitis.
  • Postherpetic neuralgia with VZV.

REFERENCES

  1. Knickelbein JE, Hendricks RL, Charukamnoetkanok P. Management of herpes simplex virus stromal keratitis: an evidence-based review. Surv Ophthalmol. 2009;54(2):226-234.

  2. Liesegang TJ. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115(2) (Suppl):S3-S12.

  3. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;1(1):CD002898.

  4. McDonald EM, de Kock J, Ram FSF. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of highquality randomized controlled trials. Antivir Ther. 2012;17(2):255-264.

  5. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1-S26.

  6. Carter WP III, Germann CA, Baumann MR. Ophthalmic diagnoses in the ED: herpes zoster ophthalmicus. Am J Emerg Med. 2008;26(5): 612-617.

CLINICAL PEARLS

  • HSV and VZV cause a wide range of ocular manifestations; early diagnosis is essential.
  • Fluorescein staining with slit lamp is critical in suspected HSV keratitis and HZO.
  • Topical antivirals for HSV keratitis; systemic oral antivirals required for HZO.
  • Ophthalmology consultation mandatory before topical steroids.
  • Hutchinson sign predicts increased risk of HZO.
  • Shingrix vaccine reduces zoster incidence, HZO, and postherpetic neuralgia duration.