DIAGNOSIS AND TREATMENT OF HERPES SIMPLEX KERATITIS UPDATE

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DIAGNOSIS AND TREATMENT OF HERPES SIMPLEX
KERATITIS UPDATE
XVI JORNADAS DE OFTALMOLOGIA DR. BENJAMIN
BOYD AUGUST, 2005
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RICHARD L. ABBOTT, M.D. PROFESSOR OF OPHTHALMOLOGY
RICHARD L.
UCSF FRANCIS I. PROCTOR FOUNDATION
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HUMANS ARE THE
HUMANS ARE THE ONLY NATURAL RESERVOIR OF HSV
HSV 1 OROPHARYNX HSV 2 GENITAL AREA
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TRIFLURIDINE
VIDARABINE
IDOXURIDINE
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HSV OCULAR DISEASE

• 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

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PRIMARY HERPES SIMPLEX

• 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)

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Look for vessicles
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Vessicles
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INFECTIOUS EPITHELIAL KERATITIS

• Corneal vessicles (PEK)
• Dendrite
• Geographic (Amoeboid) ulcers
• Marginal ulcers (Limbal KC)
• May be associated with conjunctivitis

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TREATMENTPrimary Herpes Simplex

• Oral Acyclovir
• Topical Trifluridine
• Observation (self-limited)

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TYPICAL CORNEAL DENDRITE

• Of first importance in making the clinical
  diagnosis
• Dendron (Greek- Tree)
• True ulcer extends through BM

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AVOID ROSE BENGAL IF CULTURE
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DDXDENDRITIC KERATITIS

• HSV
• HZV
• Healing epithelium
• Thimerosal (Toxicity)
• SCL

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HZV
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SOFT CONTACT LENS
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HEALING EPITHELIUM
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THIMERASOL TOXICITY
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HEALING EPITHELIUM
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HSV
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GEOGRAPHIC (AMOEBOID) ULCER

• Wide dendrite
• DDX epithelial defect scalloped border
• 4-20 of initial lesions
• /-Associated with previous steroid use

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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

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INCREASED INFLAMMATION WBC INFILTRATION
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TREATMENTInfectious Epithelial Keratitis

• Eliminate virus in short time
• Decrease potential risk for immune-mediated
  disease
• Decrease structural damage
• Clinical, culture, PCR

• Goal
• Purpose
• Diagnosis

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TREATMENTInfectious 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

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TREATMENTInfectious Epithelial Keratitis

• If slow healing, consider toxicity
• If epith ulcer persists, consider neurotrophic
• Avoid steroids

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ACYCLOVIR REGIMEN

• 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

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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

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SECTOR IRIS ATROPHY

• See in both Simplex and Zoster
• Older patient - probably Zoster
• If in doubt - treat with Zoster doses

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STROMAL KERATITIS

• 2 of initial episodes
• 20-48 of recurrent HSV
• Disciform (Immune only)
• Necrotizing (direct viral invasion)
• Metaherpetic (post-herpetic trophic ulcer)

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IMMUNE (INTERSTITIAL) STROMAL KERATITIS
(DISCIFORM)

• Cell mediated immune response to viral antigens
  in stroma or endothelium

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DISCIFORM KERATITIS

• /- Previous HSV epithelial keratitis
• Non-necrotizing
• Focal, multifocal, or diffuse area of edema
• Mild lymphocytic stromal inflammatory infiltrate-
  chronic and recurrent
• Epithelium intact
• Descemets folds and KP

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DISCIFORM KERATITIS

• Differential diagnosis
• HSV
• HZV
• Vaccinia
• Mumps
• Varicella

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STROMAL DISEASE

• Treatment goals
• Eradicate HSV
• Limit scarring
• Limit lipid deposition

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TREATMENTStromal Keratitis

• Treatment depends on severity and location of
  inflammation
• Necrotizing keratitis
• Interstitial keratitis
• Immune rings
• Limbal vasculitis
• Disciform keratitis

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TREATMENTDisciform Keratitis

• Conservative - self limited
• Oral Acyclovir 400mg 5x/day
• Topical steroid - rapid taper
• No topical antiviral (poor penetration)

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NECROTIZING STROMAL KERATITIS

• WBCs (dense infiltrate with overlying defect
• Blood vessels
• Thinning
• Scarring
• Necrosis and perforation

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TREATMENTNecrotizing Stromal Keratitis

• Never studied by HEDS
• Acyclovir and topical steroids
• Taper slowly
• Maintain steroid at lowest dose
• Recurrence into visual axis
• Surgery

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STEROID TAPER

• Pred Acetate qid gt bid gt qd gt qod
• 4-6 weeks between steps
• Look for KP or edema
• Switch to weaker steroid
• Ask if redness when miss drop

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NEUROTROPIC KERATOPATHYPOST HERPETIC
EROSION(Metaherpetic Keratitis)

• Follows severe epithelial disease
• Basement membrane damage
• Non-healing epithelial defect
• Clinical course

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TREATMENTNeurotrophic Keratopathy

• Goal
• Purpose
• Diagnosis

• Decrease exposure to toxic substances
• Increase lubrication
• Decrease risk 2º infection
• Decrease risk of stromal melting
• Rolled borders of epithelium

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TREATMENTTrophic Epithelial Defect

• Protect ocular surface
• Non preserved lubricants
• Therapeutic contact lens
• Gentle debridement
• Amniotic membrane
• Tarsorrhaphy

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ENDOTHELIITIS

• Inflammatory reaction of endothelium
• Corneal stromal edema without infiltrate
  (disciform, diffuse, linear)
• KP, Stromal/epithelial edema, iritis
• Responds to steroids

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REACTIVATION HSV

• Hormonal changes
• Ultraviolet light
• Surgery of eye
• Systemic infection
• Latanoprost

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REACTIVATION HSV

• Stress
• Fever
• Immunosuppression
• Trauma (CL wear)
• 9.6 first year
• 36 _at_ 5 years
• 63 within 20 years
• HEDS 18 recurrence rate

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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

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PROPHYLAXIS FOR HSV KERATOPLASTY

• Use oral acyclovir
• Pre-op 400mg qid for 3 days
• Post-op 400mg qid for 7 days 400mg bid for
  3months
• No controlled studies available

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TREATMENTStromal Keratitis

• If corneal perforation
• Surgical adhesive
• Lamellar patch graft
• PKP
• Use of oral Acyclovir

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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

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FAMCICLOVIR

• MOA similar to Acyclovir
• Inhibits HSV DNA synthesis
• Rapidly absorbed from GI tract
• Intracellular 1/2 life is 10-20 times
  longer
• Lactose intolerance

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FAMCICLOVIR

• Dose 500mg bid-tid
• Side effects similar to Acyclovir
• More expensive cost

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CIDOFOVIRPENCICLOVIR

• Variation in chemical structure
• Inhibit DNA polymerase
• Less resistance

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VALTREX ANDFAMVIR

• Not more effective than Acyclovir
• Cost issue
• Compliance issue

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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