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