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Ocular Adverse Events

Adverse Event Definition and Evaluation - Ocular contact transmission (Ocular vaccinia)

Definition of Suspicious Lesion(s)

  • New onset red eye and/or lesions suspicious for vaccinia (papules, vesicles, pustules or ulcerations)
  • History of close contact with a vaccinee who received smallpox vaccine ≤ 30 days before exposure
  • Lesions typically appear 3-9 days after exposure to vaccinee
  • Types of eye involvement1
    • Periocular
    • Blepharitis
    • Conjunctivitis
    • Keratitis

Evaluation

  • Assess for risk factors for smallpox vaccine adverse events (i.e., atopic dermatitis, immune-compromise, pregnancy, infant, topical ocular steroid use)
  • Patient history and eye exam using universal precautions, to include:
    • visual acuity
    • presence or absence of lesions and conjunctival inflammation
    • presence and severity of corneal and lid involvement
    • Magnified exam of eye surface with slit lamp and fluorescein exam for corneal epithelial defects
  • Ophthalmologic consultation
  • Obtain digital photos of involved eye
  • Obtain PCR and culture for vaccinia virus at military or civilian lab that can provide results within 1-2 days
  • Smears of mucopurulent drainage (PMN cells c/w vaccinia)
  • Scrapings of vaccinial lesions (eosinophilic cytoplasmic inclusion bodies, or Guarneri bodies c/w vaccinia)
  • Obtain cultures to r/o HSV, varicella, and bacteria
  • Evaluate for other potential serious adverse events (i.e., eczema vaccinatum, progressive vaccinia, generalized vaccinia, myopericarditis)

Treatment and Management

  • Document.
  • File VAERS report if vaccinia confirmed or equivocal.
  • Educate on precautionary measures to limit spread including water free hand washing.
  • Treat with non-sedating antihistamines to avoid scratching and further spread.
  • Treat based on type of eye involvement and severity:
    • Periocular2
    • Blepharitis (mild and severe)3
    • Conjunctivitis with or without blepharitis, but without keratitis (mild and severe)4
    • Keratitis only5
    • Keratitis with mild or moderate blepharitis or conjunctivitis6
    • Keratitis with severe blepharitis and/or conjunctivitis7

Future Dose

If you retrieved virus on day of ocular splash, and if case is confirmed with a vaccinial lesion lasting several days, individual is considered immunized.

Comments

Consultation Information

  1. Clinical: Military health care providers (or civilian providers treating a DoD healthcare beneficiary) - call the Worldwide DHA Immunization Healthcare Support Center at (877) GETVACC (438-8222).
  2. Information on obtaining viral PCR and culture specimens: Available on the CDC website.
  3. PCR (polymerase chain reaction assay for vaccinia) is available through military or state regional laboratories participating in Emergency Response Lab Network. If unable to obtain prompt Local support for PCR and culture, contact the Immunization Healthcare Division by email or telephone. After hours, Call the Worldwide DHA Immunization Healthcare Support Center at (877) GET-VACC or (877) 438-8222.
  4. VIG8 consultation
    Call (888) USA-RIID or (301) 619-2257.
    IHD Clinical Services will arrange multidisciplinary case discussion via conference call9 including:
    • Referring provider
    • Ophthalmologist directly involved with case
    • Ophthalmologist consultant
    • Pharmacy consultant
    • IHD Clinical Services physician
    • USAMRIID consultant
    • CDC physician on call
    • IHD Clinical Services case manager
    VIG is typically contraindicated if keratitis is present. [Consider only if there is a co-morbid condition (eczema vaccinatum or progressive vaccinia)].
  5. Ophthalmology consultation:
    • For any suspected ocular transmission
    • When optical antirvirals10 are used
    • When topical steroids are used

Link to photos
Keratitis
Inadvertent inoculation, includes ocular
References
www.cdc.gov/mmwr/PDF/rr/rr5204.pdf

Footnote  Topic  Details 
 1 Types of Eye Involvement
  1. Periocular (generally above the brow or below the inferior orbital rim): Papules, vesicles or pustules not involving the ocular adnexa, lids, lid margins, or canthi.
  2. Blepharitis (lid involvement):
    Mild - few pustules, mild edema, no fever.
    Severe - pustules, edema, hyperemia, lymphadenopathy (preauricular and/or submandibular), cellulitis, fever.
  3. Conjunctivitis (involvement of membrane that lines inner surface of the eyelid and exposed surface of the eyeball; excluding the cornea):
    Mild - mild hyperemia and/or edema, no membranes or focal lesions.
    Severe - marked hyperemia, edema, membranes, focal lesions, lymphadenopathy (preauricular and/or submandibular), fever.
  4. Keratitis (corneal involvement):
    Mild - gray epithelitis, no epithelial defect, no stromal haze or infiltrate (no cloudy cornea)
    Moderate - epithelial defect
    Severe - ulcer, stromal haze or infiltrate (cloudy cornea). 
 2 Treatment for Periocular Involvement Periocular lesions only (no lid involvement or lesions in eye
  • Close observation.
  • Consider ophthalmology consultation to assist in management.
 3 Treatment for Blephartis Mild Blepharitis
  • Begin topical antiviral prophylaxis10
    • Topical Trifluridine (Viroptic®)- 5 times/day (every four hours while awake) for up to 14 days or until all periocular lesions have healed and scars have fallen off. If no improvement or symptoms worsen after 24-48 hours consider increasing to 9 times/day (every two hours while awake) 
  • Moderate/Severe Blepharitis
  • Begin topical antiviral prophylaxis10
    • Topical Trifluridine - 5 times/day (every four hours while awake) for up to 14 days or until all periocular lesions have healed and scabs have fallen off. If no improvement or symptoms worsen after 24-48 hours consider increasing to 9 times/day (every two hours while awake)
  • Ophthalmology consultation in 12-24 hours or sooner to evaluate and assist in management.
  • Consider VIG8 consultation. [Call (888) USA-RIID or (301) 619-2257.]
 4 Treatment for Conjunctivitis Mild Conjunctivitis (no visible lesions in or near the eye)
  • Consider differential diagnosis for new red eye with high index of suspicion for vaccinia infection.
  • Close observation for development of suspicious lesions.
  • Ophthalmology consultation as indicated to evaluate for possible vaccinia vs. other unrelated causes.
  • Further treatment as indicated by ophthalmic exam.

Mild Conjunctivitis with suspicious lesions in or near the eye (no corneal lesions)

  • Begin topical antiviral prophylaxis10
    • Topical Trifluridine - 5 times/day (every four hours while awake) for up to 14 days or until all periocular lesions have healed and scabs have fallen off. If no improvement or symptoms worsen after 24-48 hours consider increasing to 9 times/day (every two hours while awake)
  • Urgent Ophthalmology consultation

Severe Conjunctivitis with suspicious lesions in or near the eye (no corneal lesions)

  • Topical antiviral prophylaxis10
    • Topical Trifluridine - 5 times/day (every four hours while awake) for up to 14 days or until all periocular lesions have healed and scabs have fallen off. If no improvement or symptoms worsen after 24-48 hours consider increasing to 9 times/day (every two hours while awake)
  • Emergent Ophthalmology consultation
  • Consider VIG8 consultation. (Call (888) USA-RIID or (301) 619-2257.)
 5 Treatment for Keratitis only Keratitis only
  • Emergent ophthalmology consultation to evaluate and assist with management.
  • VIG8 not indicated [Consider when there is a co-morbid condition (eczema vaccinatum or progressive vaccinia)].
  • Consider topical ophthalmic antibacterial prophylaxis in the presence of keratitis.
  • Begin topical antiviral treatment10
    • To minimize progression and begin resolution of vaccinia infection in cornea and conjunctiva:
      • Topical Trifluridine - 9 times/day (every two hours while awake) for up to 14 days or until all lesions have healed. Hyperemia is an expected consequence of therapy, especially after 14 days use.
      • After corneal epithelium has healed, consider use of topical steroids under supervision of an ophthalmologist.
 6 Treatment for Keratitis with mild or moderate blepharitis or conjunctivitis Keratitis with mild or moderate blepharitis or conjunctivitis
  • Emergent ophthalmology consultation.
  • Begin topical antiviral treatment10
    • To minimize progression and begin resolution of vaccinia infection in cornea and conjunctiva:
      • Topical Trifluridine - 9 times/day (every two hours while awake) for up to 14 days or until all lesions have healed. Hyperemia is an expected consequence of therapy, especially after 14 days use.
      • Observe for progressive disease.
 7 Treatment for Keratitis with severe blepharitis and/or conjunctivitis Keratitis with severe blepharitis and/or conjunctivitis
  • Begin topical antiviral treatmemt10
    • Topical Trifluridine - 9 times/day (every two hours while awake) for up to 14 days or until all lesions have healed. Hyperemia is an expected consequence of therapy, especially after 14 days use.
  • Consider VIG8
 8  VIG VIG consultationcall (888) USA-RIID or (301) 619-2257.
  • VIG is typically contraindicated if keratitis is present. [Consider only if there is a co-morbid condition (eczema vaccinatum or progressive vaccinia).]
  • Consider consultation with Allergy and Immunology or Infectious Disease consultants regarding implementation of VIG.
 9

Multidisciplinary Case Discussion via Conference Call

IHD Clinical Services will arrange multidisciplinary conference call

The following information will be provided to participants:

  • time scheduled
  • number of participants
  • conference ID
  • Toll free dial in number
  • Participant code

[Should you need assistance during your conference, please press # then 0 for a list of menu options including Specialist assistance.]

IHD Clinical Services Physician:
Call Worldwide DHA Immunization Healthcare Support Center at (877) GETVACC (438-8222) for provider and number. 

 10

Topical antivirals

 Available Topical antiviral agents

Trifluridine (Viroptic®) and vidarabine (Vira-A®) are not approved by FDA for treatment of vaccinia disease, although the product labels for trifluridine and vidarabine state that the drugs have in vitro and in vivo activity against vaccinia virus.

Vidarabine is no longer being manufactured, but supplies might be available in certain areas.

Cidofovir, which is active against orthopox viruses and suggested for possible treatment of smallpox, has not been evaluated for use in ocular vaccinia or keratitis.

Last Updated: August 26, 2022
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