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DIAGNOSIS AND
TREATMENT OF
HERPES SIMPLEX
KERATITIS
UPDATE
XVI JORNADAS DE OFTALMOLOGIA
DR. BENJAMIN BOYD
AUGUST, 2005
RICHARD L.
RICHARD L. ABBOTT, M.D.
PROFESSOR OF OPHTHALMOLOGY
UCSF
FRANCIS I. PROCTOR FOUNDATION
HUMANS
ARE THE
HUMANS ARE THE ONLY
NATURAL
RESERVOIR OF HSV
HSV 1 OROPHARYNX
HSV 2 GENITAL AREA
TRIFLURIDINE
VIDARABINE
IDOXURIDINE
HSV OCULAR DISEASE
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Approx. 1/2 million people in U.S.
Approx. 20-45% of world population
Approx. 50,000 active episodes annually
Approx. 20,000 new cases annually
By age 5….60% of population infected
Only 6% develop clinical manifestations
PRIMARY
HERPES SIMPLEX
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Acquired from environment (oral lesions, saliva)
Not from viral latency
Unilateral vesicular blepharoconjuntivitis
Pruritic vessicles of lids, skin, eyelid margin
Follicular conjunctivitis
Palpable preauricular lymph node
PEK (RARE dendrite)
Look for vessicles
Vessicles
INFECTIOUS
EPITHELIAL KERATITIS
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Corneal vessicles (PEK)
Dendrite
Geographic (Amoeboid) ulcers
Marginal ulcers (Limbal KC)
May be associated with
conjunctivitis
TREATMENT
Primary Herpes Simplex
• Oral Acyclovir
• Topical Trifluridine
• Observation (self-limited)
TYPICAL CORNEAL
DENDRITE
Of first importance in making the
clinical diagnosis
Dendron (Greek- “Tree”)
True ulcer – extends through BM
AVOID ROSE BENGAL IF CULTURE
DDX:
DENDRITIC KERATITIS
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HSV
HZV
Healing epithelium
Thimerosal (Toxicity)
SCL
HZV
SOFT CONTACT LENS
HEALING EPITHELIUM
THIMERASOL TOXICITY
HEALING EPITHELIUM
HSV
GEOGRAPHIC
(AMOEBOID) ULCER
• “Wide” dendrite
• DDX epithelial defect – scalloped
border
• 4-20% of initial lesions
• +/-Associated with previous
steroid use
LIMBAL (MARGINAL)
HSV-I KERATITIS
• Atypical presentation
• More resistant to Rx
• DDX: Staph marginal infiltrate
– No epithelial defect
– Progress circumferential
– Associated with blepharitis
– Typical location 2, 4, 8, 10
INCREASED INFLAMMATION
WBC INFILTRATION
TREATMENT
Infectious Epithelial Keratitis
• Goal:
– Eliminate virus in short
time
• Purpose:
– Decrease potential risk for
immune-mediated disease
– Decrease structural damage
• Diagnosis: – Clinical, culture, PCR
TREATMENT
Infectious Epithelial Keratitis
• Gentle debridement
• Topical antivirals (10-14 days max)
– Viroptic 1% q 2h or
– Vira A 5X/day
• If no response 72 hours – STOP
• Resistance rate - 3%
TREATMENT
Infectious Epithelial Keratitis
• If slow healing, consider toxicity
• If epith ulcer persists, consider
neurotrophic
• Avoid steroids
ACYCLOVIR REGIMEN
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400 mg 5x/day for 10-14 days
Reduce to b.i.d. for 10 days
Very safe
Headaches, GI upset
Watch dose renal disease
HSV IRIDOCYCLITIS
• 1-9% of all non-traumatic anterior
uveitis
• May occur independently
• Live virus in aqueous
• Average time to resolution: 4 weeks
• Treat with topical steroids,
cycloplegics, and PO Acyclovir
• Watch IOP – Trabeculitis
SECTOR IRIS ATROPHY
• See in both Simplex and Zoster
• Older patient - probably Zoster
• If in doubt - treat with Zoster doses
STROMAL KERATITIS
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2% of initial episodes
20-48% of recurrent HSV
Disciform (Immune only)
Necrotizing (direct viral invasion)
Metaherpetic (post-herpetic trophic
ulcer)
IMMUNE
(INTERSTITIAL)
STROMAL KERATITIS
(DISCIFORM)
• Cell mediated immune response
to viral antigens in stroma or
endothelium
DISCIFORM KERATITIS
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+/- Previous HSV epithelial keratitis
Non-necrotizing
Focal, multifocal, or diffuse area of edema
Mild lymphocytic stromal inflammatory
infiltrate- chronic and recurrent
• Epithelium intact
• Descemet’s folds and KP
DISCIFORM KERATITIS
• Differential diagnosis
– HSV
– HZV
– Vaccinia
– Mumps
– Varicella
STROMAL DISEASE
• Treatment goals
– Eradicate HSV
– Limit scarring
– Limit lipid deposition
TREATMENT
Stromal Keratitis
• Treatment depends on severity
and location of inflammation
– Necrotizing keratitis
– Interstitial keratitis
– Immune rings
– Limbal vasculitis
– Disciform keratitis
TREATMENT
Disciform Keratitis
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Conservative - self limited
Oral Acyclovir 400mg 5x/day
Topical steroid - rapid taper
No topical antiviral (poor
penetration)
NECROTIZING
STROMAL KERATITIS
• WBC’s (dense infiltrate
with overlying defect
• Blood vessels
• Thinning
• Scarring
• Necrosis and perforation
TREATMENT
Necrotizing Stromal Keratitis
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Never studied by HEDS
Acyclovir and topical steroids
Taper slowly
Maintain steroid at lowest dose
Recurrence into visual axis
Surgery
STEROID TAPER
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Pred Acetate qid > bid > qd > qod
4-6 weeks between steps
Look for KP or edema
Switch to weaker steroid
Ask if redness when miss drop
NEUROTROPIC
KERATOPATHY
POST HERPETIC EROSION
(Metaherpetic Keratitis)
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Follows severe epithelial disease
Basement membrane damage
Non-healing epithelial defect
Clinical course
TREATMENT
Neurotrophic Keratopathy
• Goal:
– Decrease exposure to toxic
substances
– Increase lubrication
• Purpose:
– Decrease risk 2º infection
– Decrease risk of stromal melting
• Diagnosis: – Rolled borders of epithelium
TREATMENT
Trophic Epithelial Defect
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Protect ocular surface
Non preserved lubricants
Therapeutic contact lens
Gentle debridement
Amniotic membrane
Tarsorrhaphy
ENDOTHELIITIS
• Inflammatory reaction of
endothelium
• Corneal stromal edema without
infiltrate (disciform, diffuse, linear)
• KP, Stromal/epithelial edema, iritis
• Responds to steroids
REACTIVATION HSV
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Hormonal changes
Ultraviolet light
Surgery of eye
Systemic infection
Latanoprost
REACTIVATION HSV
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Stress
Fever
Immunosuppression
Trauma (CL wear)
9.6% first year
36% @ 5 years
63% within 20 years
HEDS: 18% recurrence rate
RECURRENT HSV
• Reactivation in latently infected cells
• Disease pattern affected by:
– Strain of virus (Can block subsequent
infection by another strain)
– Genetic constitution of host
PROPHYLAXIS FOR
HSV KERATOPLASTY
• Use oral acyclovir
– Pre-op:
– Post-op:
400mg qid for 3 days
400mg qid for 7 days
400mg bid for 3months
• No controlled studies available
TREATMENT
Stromal Keratitis
• If corneal perforation:
– Surgical adhesive
– Lamellar patch graft
– PKP
Use of oral Acyclovir
VALACYCLOVIR
(Valtrex)
• Absorbed rapidly from GI tract
• Converted into Acyclovir
(Prodrug)
• Plasma levels 3 times higher
than same dose with Acyclovir
• Do Not Use with renal disease
and HIV
• Dose: 1 Gram qd
FAMCICLOVIR
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MOA similar to Acyclovir
Inhibits HSV DNA synthesis
Rapidly absorbed from GI tract
Intracellular 1/2 life is
10-20 times longer
• Lactose intolerance
FAMCICLOVIR
• Dose: 500mg bid-tid
• Side effects similar to Acyclovir
• More expensive cost
CIDOFOVIR
PENCICLOVIR
• Variation in chemical structure
• Inhibit DNA polymerase
• Less resistance
VALTREX AND
FAMVIR
• Not more effective than Acyclovir
• Cost issue
• Compliance issue
HEDS STUDY RESULTS
• Oral antiviral prophylaxis reduces recurrences
of epithelial and of stromal keratitis
• Use of topical steroids is of benefit in stromal
keratitis
• Use of oral acyclovir may be of help in
iridocyclitis
• Prophylactic oral acyclovir helps prevent
recurrences of herpetic keratitis, particularly
stromal with a history of recurrence