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Herpes Eye Infections
Rachel Marinch Carpenter, MD
William Fosmire, MD
image BASICS
  • Eye infection (blepharitis, conjunctivitis, keratitis, stromal keratitis, uveitis, retinitis, glaucoma, or optic neuritis) caused by herpes simplex virus (HSV) types 1 or 2 or varicella-zoster virus (VZV, also known as human herpes virus type 3 [HHV3])
  • Categories
    • HSV: can affect many parts of the eye but most often affects the cornea (herpes keratoconjunctivitis); HSV1 > HSV2; can be further divided into primary and recurrent
    • VZV: when VZV is reactivated and affects the ophthalmic division of the 5th cranial nerve, this is known as herpes zoster ophthalmicus (HZO), a type of shingles
  • System(s) affected: eye, skin, CNS (neonatal)
  • Predominant age: HSV-mean age of onset 37.4 years but can occur at any age, including primary infection in newborns; VZV usually advancing age (>50 years)
  • Predominant sex: HSV—male = female; HZO—female > male
  • HSV keratitis: In the United States, approximated at 18.2 per 100,000 person-years. Incidence is 1.5 million per year worldwide (1).
  • VZV: 1 million new cases of shingles per year in the United States; 25-40% develop ophthalmic complications. Temporary keratitis is most common.
  • Ocular HSV prevalence estimated at 500,000 in the United States (1)
  • VZV: Prevalence of herpes zoster infection is 20-30%. Ocular involvement in 50% if not treated with antivirals (2). Overall lifetime prevalence of HZO: 1%
  • HSV and VZV are Herpesviridae dsDNA viruses
  • HSV: primary infection from direct contact with infected person via saliva, genital contact, or birth canal exposure (neonates)
    • Primary infection may lead to severe disease in neonates, including eye, skin, CNS, and disseminated disease.
    • Recurrent infection is more common overall cause of herpetic eye infections.
  • VZV: Primary infection from direct contact with infected person may cause varicella (“chickenpox”) and/or lead to a latent state within trigeminal ganglia.
    • Reactivation of the virus may affect any dermatome (resulting in herpes zoster or “shingles”), including the ophthalmic branch (HZO).
  • HSV: personal history of HSV or close contact with HSV-infected person
    • General risk factors for reactivation: stress, trauma, fever, UV light exposure, other viral infections
    • Risk factors for HSV keratitis: UV laser eye treatment, some topical ocular medications such as prostaglandin analogues and primary/secondary immunosuppression
  • HZO
    • History of varicella infection, advancing age (>50 years), sex (female > male), acute/painful prodrome, trauma, stress, immunosuppression (1,3)
  • Contact precautions with active lesions (HSV and VZV)
  • VZV can be spread to those who have not had chickenpox and are not immunized.
  • Varicella vaccination (Zostavax) (VZV only): single 0.65 mL SC dose; no booster. Recommended by the CDC for all persons age ≥60 years. Reduces incidence of herpes zoster by 51% and HZO for 49%; also significantly decreases rates of post-herpetic neuralgia (PHN) (4)
  • Acyclovir can be used prophylactically to prevent recurrence of ocular HSV.
  • HSV immunization currently being researched (1)
Pregnancy Considerations
  • Pregnant women without history of chickenpox should avoid contact with persons with active zoster.
  • Pregnancy increases risk of recurrence of HSV/VZV.
  • Live vaccine (Zostavax) is contraindicated during pregnancy.
Primary and secondary immunocompromised states
  • Varies according to the virus and ocular structures involved
    • HSV most commonly affects the corneal epithelium (1)[A].
    • VZV most commonly affects corneal stroma and uvea (3)[A].
  • Typically unilateral in presentation
    • HZO presents as early as 1 to 2 days after unilateral vesicular eruption in a dermatomal pattern (3)[A].
  • Decreased visual acuity
  • Conjunctival injection near the limbus
  • Decreased corneal sensation
  • Slit-lamp exam
    • Fluorescein and rose bengal stain: Dendritic corneal lesions most often seen in HSV, followed by stromal keratitis, corneal edema, or infiltrate (2)[C].
    • Stromal keratitis often seen in HZO, although dendritic lesions may form (2)[A].
  • Any other cause of red, painful eye
    • Bacterial, fungal, allergic, or other viral conjunctivitis
    • Acute angle-closure glaucoma
  • Corneal abrasion, recurrent corneal erosion, toxic conjunctivitis
  • Temporal arteritis
  • Trigeminal neuralgia
Initial Tests (lab, imaging)
  • Typically none needed, as diagnosis is primarily based on history and physical exam (3)[A]
  • Other
    • Corneal swab for HSV DNA by polymerase chain reaction (PCR) (PPV = 96%)
    • If vesicle present, can perform a Tzanck smear for VZV or HSV (multinucleated giant cells)
    • Antibody titers to assess exposure only; DFA (direct fluorescent antibody); tissue culture
  • Avoid contact with nonimmune people.
  • No contact lenses should be worn during treatment period.
  • Cool compresses
  • Artificial tears
  • Oral pain medications
First Line
  • HSV corneal epithelial disease
    • Trifluridine 1%: apply 1 drop q2h while awake to a max of 9 drops daily until reepithelialization occurs, then 1 drop q4h for another 7 days
    • Acyclovir: 400 mg PO 5 times per day for 10 days
    • Ganciclovir 0.15% gel: apply 1 drop in eye q3h while awake, ~5 times daily, until reepithelialization occurs, then 1 drop q8h for 7 days
    • Vidarabine 3% ointment (Vira-A): apply 0.5 inch into lower conjunctival sac 5 times daily q3h, until reepithelialization occurs.
    • Trifluridine and acyclovir cure about 90% of treated eyes within 2 weeks with no significant differences in effectiveness (5)[A].
    • Evidence conflicting as to whether ganciclovir is as good as or better than acyclovir (5)[A].
    • Epithelial débridement by an ophthalmologist: may accelerate healing in combination with treatment as above (5)[A]
    • Avoid topical steroids.
  • P.475

  • Utility of PO antivirals unclear HSV stromal keratitis or uveitis (without epithelial disease): combination of antiviral and steroid treatment; requires ophthalmology evaluation
    • Prednisolone acetate: 1% drops QID with slow taper (6)[A]
    • Consider systemic steroids in severe uveitis (6)[A].
    • Trifluorothymidine: 1% drops QID for prophylaxis while on topical steroids
  • HZO
    • Valacyclovir (Valtrex) 1 g PO TID for 7 to 10 days or famciclovir (Famvir) 500 mg PO TID for 7 to 10 days or acyclovir 800 mg PO 5 times a day for 7 to 10 days
    • Valacyclovir and famciclovir result in significant reduction in PHN compared to acyclovir (number needed to treat [NNT] = 3) with equivalent efficacy (7)[A]
    • Topical antibiotic ophthalmic ointment to protect ocular surfaces (e.g., Bacitracin, Polymyxin): 0.5-inch ribbon BID to TID for 7 to 10 days (8)[C]
    • If immunocompromised: acyclovir 10 to 15 mg/kg IV q8h for 10 days
    • Prednisolone acetate: 1% drops QID with slow taper with an ophthalmologist (8)[C]
  • Cycloplegic agent if anterior uveitis present; intraocular pressure-lowering agent if necessary
Second Line
  • HSV: acyclovir 2 g/day PO in divided doses over 10 days in patients intolerant of topical antivirals
  • Topical idoxuridine, acyclovir, brivudine, although approved internationally, are not approved for use in the United States.
  • Concomitant treatment with interferon may also improve outcomes but is not currently available.
Emergent or urgent ophthalmology referral, depending on severity of disease
  • Recurrent HSV requires suppressive therapy:
    • Acyclovir 400 mg PO every day or BID or valacyclovir 500 mg PO daily (9)[C]
  • HZO leading to PHN is very common and can be treated with gabapentin or pregabalin, TCAs, opioids, and/or lidocaine gel.
Corneal transplantation for severe scarring or perforation
Admission Criteria/Initial Stabilization
  • Severe systemic VZV disease
  • Systemic HSV in neonates —see “Herpes Simplex Virus, Pediatric”
Discharge Criteria
Resolution of systemic disease
Patient Monitoring
  • Monitor with slit-lamp exam q1-2d until improvement, then q3-4d until epithelial defect resolves.
  • Weekly after epithelial disease resolves until off topical antivirals
Educate patients about the importance of early recognition of recurrent symptoms and need for prompt evaluation and treatment.
  • Many cases are self-limited but, depending on the ocular structure involved, can lead to permanent blindness, especially in the setting of recurrent disease.
  • Ocular HSV is the number one cause of infectious blindness worldwide (1).
  • Recurrent ocular HSV
    • HSV epithelial disease without treatment
    • Without sequelae, 40% resolve.
    • With treatment, 90-95% resolve without complication.
Pediatric Considerations
  • Neonatal primary HSV often disseminated, with high mortality rate; 37% develop vision worse than 20/200
  • Pediatric cases more likely to be bilateral (26%); recurrent (48% in 15 months); and may cause amblyopia
1. Faroog AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Opththalmol. 2012;57(5):448-462.
2. Carter WP III, Germann CA, Baumann MR. Ophthalmic diagnoses in the ED: herpes zoster ophthalmicus. Am J Emerg Med. 2008;26(5):612-617.
3. Liesegang TJ. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115(2 Suppl):S3-S12.
4. Gelb LD. Preventing herpes zoster through vaccination. Ophthalmology. 2008;115(2 Suppl):S35-S38.
5. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;(1):CD002898.
6. Knickelbein JE, Hendricks RL, Charukamnoetkanok P. Management of herpes simplex virus stromal keratitis: an evidence-based review. Surv Ophthalmol. 2009;54(2):226-234.
7. McDonald EM, de Kock J, Ram FS. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of highquality randomized controlled trials. Antivir Ther. 2012;17(2):255-264.
8. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1-S26.
9. de Rojas Silva MV, Díez-Feijóo E, Javaloy J, et al. Prophylactic perioperative antiviral therapy for LASIK in patients with inactive herpetic keratitis. J Refract Surg. 2006;22(4):404-406.
Additional Reading
Rowe AM, St Leger AJ, Jeon S, et al. Herpes keratitis. Prog Retin Eye Res. 2013;32:88-101.
See Also
  • Algorithm: Eye Pain
  • Topic: Herpes Simplex
  • Topic: Herpes Simplex Virus, Pediatric
  • Topic: Herpes Zoster
  • B00.50 Herpesviral ocular disease, unspecified
  • B02.30 Zoster ocular disease, unspecified
  • B00.52 Herpesviral keratitis
Clinical Pearls
  • HSV and VZV can lead to a wide array of ocular manifestations, ranging from self-limited disease to potentially vision-threatening disease and complications.
  • A slit-lamp exam with fluorescein stain should be performed on all patients with possible HSV keratitis or HZO.
  • Topical antiviral treatment is appropriate for HSV, but systemic PO antiviral treatment is necessary for HZO.
  • An ophthalmologist should be consulted before prescribing topical steroids. All HZO patients should be referred to an ophthalmologist.
  • Hutchinson sign (vesicular lesion on nose from VZV) is a strong indicator of HZO.
  • Zostavax is effective at preventing zoster and HZO as well as decreasing the duration of PHN.