DIAGNOSIS AND TREATMENT OF HERPES SIMPLEX
KERATITIS UPDATE
XVI JORNADAS DE OFTALMOLOGIADR. BENJAMIN BOYD
AUGUST, 2005
RICHARD L.RICHARD L. ABBOTT, M.D.PROFESSOR OF OPHTHALMOLOGY
UCSFFRANCIS I. PROCTOR FOUNDATION
HUMANS ARE THE HUMANS ARE THE ONLY NATURAL RESERVOIR OF HSV
HSV 1 OROPHARYNXHSV 2 GENITAL AREA
VIDARABINETRIFLURIDINE
IDOXURIDINE
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
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)
Look for vessicles
Vessicles
INFECTIOUS EPITHELIAL KERATITIS
• Corneal vessicles (PEK)• Dendrite• Geographic (Amoeboid) ulcers• Marginal ulcers (Limbal KC)
• May be associated with conjunctivitis
TREATMENTPrimary 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
• 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 INFLAMMATIONWBC INFILTRATION
TREATMENTInfectious Epithelial Keratitis• Goal:
• Purpose:
• Diagnosis:
– Eliminate virus in short time– Decrease potential risk for
immune-mediated disease– Decrease structural damage
– Clinical, culture, PCR
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%
TREATMENTInfectious Epithelial Keratitis• If slow healing, consider toxicity• If epith ulcer persists, consider
neurotrophic• Avoid steroids
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
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• 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• +/- 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
TREATMENTStromal Keratitis
• Treatment depends on severity and location of inflammation– Necrotizing keratitis– Interstitial keratitis– Immune rings– Limbal vasculitis– Disciform keratitis
TREATMENTDisciform Keratitis
• 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
TREATMENTNecrotizing Stromal Keratitis
• Never studied by HEDS• Acyclovir and topical steroids• Taper slowly• Maintain steroid at lowest dose• Recurrence into visual axis • Surgery
STEROID TAPER• 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)
• Follows severe epithelial disease• Basement membrane damage• Non-healing epithelial defect• Clinical course
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
TREATMENTTrophic Epithelial Defect
• 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• Hormonal changes• Ultraviolet light• Surgery of eye• Systemic infection• Latanoprost
REACTIVATION HSV• 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: 400mg qid for 3 days–Post-op: 400mg qid for 7 days
400mg bid for 3months• No controlled studies available
TREATMENTStromal 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• 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
CIDOFOVIRPENCICLOVIR
• Variation in chemical structure• Inhibit DNA polymerase• Less resistance
VALTREX ANDFAMVIR
• 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
