Title: DIAGNOSIS AND TREATMENT OF HERPES SIMPLEX KERATITIS UPDATE
1DIAGNOSIS AND TREATMENT OF HERPES SIMPLEX
KERATITIS UPDATE
XVI JORNADAS DE OFTALMOLOGIA DR. BENJAMIN
BOYD AUGUST, 2005
2RICHARD L. ABBOTT, M.D. PROFESSOR OF OPHTHALMOLOGY
RICHARD L.
UCSF FRANCIS I. PROCTOR FOUNDATION
3HUMANS ARE THE
HUMANS ARE THE ONLY NATURAL RESERVOIR OF HSV
HSV 1 OROPHARYNX HSV 2 GENITAL AREA
4TRIFLURIDINE
VIDARABINE
IDOXURIDINE
5HSV 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
6PRIMARY 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)
7Look for vessicles
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10Vessicles
11INFECTIOUS EPITHELIAL KERATITIS
- Corneal vessicles (PEK)
- Dendrite
- Geographic (Amoeboid) ulcers
- Marginal ulcers (Limbal KC)
- May be associated with conjunctivitis
12TREATMENTPrimary Herpes Simplex
- Oral Acyclovir
- Topical Trifluridine
- Observation (self-limited)
13TYPICAL CORNEAL DENDRITE
- Of first importance in making the clinical
diagnosis - Dendron (Greek- Tree)
- True ulcer extends through BM
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15AVOID ROSE BENGAL IF CULTURE
16DDXDENDRITIC KERATITIS
- HSV
- HZV
- Healing epithelium
- Thimerosal (Toxicity)
- SCL
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18HZV
19SOFT CONTACT LENS
20HEALING EPITHELIUM
21THIMERASOL TOXICITY
22HEALING EPITHELIUM
23HSV
24GEOGRAPHIC (AMOEBOID) ULCER
- Wide dendrite
- DDX epithelial defect scalloped border
- 4-20 of initial lesions
- /-Associated with previous steroid use
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27LIMBAL (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
28INCREASED INFLAMMATION WBC INFILTRATION
29TREATMENTInfectious Epithelial Keratitis
- Eliminate virus in short time
- Decrease potential risk for immune-mediated
disease - Decrease structural damage
- Clinical, culture, PCR
30TREATMENTInfectious 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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34TREATMENTInfectious Epithelial Keratitis
- If slow healing, consider toxicity
- If epith ulcer persists, consider neurotrophic
- Avoid steroids
35ACYCLOVIR 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
36HSV 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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39SECTOR IRIS ATROPHY
- See in both Simplex and Zoster
- Older patient - probably Zoster
- If in doubt - treat with Zoster doses
40STROMAL 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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42IMMUNE (INTERSTITIAL) STROMAL KERATITIS
(DISCIFORM)
- Cell mediated immune response to viral antigens
in stroma or endothelium
43DISCIFORM 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
44DISCIFORM KERATITIS
- Differential diagnosis
- HSV
- HZV
- Vaccinia
- Mumps
- Varicella
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46STROMAL DISEASE
- Treatment goals
- Eradicate HSV
- Limit scarring
- Limit lipid deposition
47TREATMENTStromal Keratitis
- Treatment depends on severity and location of
inflammation - Necrotizing keratitis
- Interstitial keratitis
- Immune rings
- Limbal vasculitis
- Disciform keratitis
48TREATMENTDisciform Keratitis
- Conservative - self limited
- Oral Acyclovir 400mg 5x/day
- Topical steroid - rapid taper
- No topical antiviral (poor penetration)
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50NECROTIZING STROMAL KERATITIS
- WBCs (dense infiltrate with overlying defect
- Blood vessels
- Thinning
- Scarring
- Necrosis and perforation
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54TREATMENTNecrotizing Stromal Keratitis
- Never studied by HEDS
- Acyclovir and topical steroids
- Taper slowly
- Maintain steroid at lowest dose
- Recurrence into visual axis
- Surgery
55STEROID 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
56NEUROTROPIC KERATOPATHYPOST HERPETIC
EROSION(Metaherpetic Keratitis)
- Follows severe epithelial disease
- Basement membrane damage
- Non-healing epithelial defect
- Clinical course
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59TREATMENTNeurotrophic Keratopathy
- Decrease exposure to toxic substances
- Increase lubrication
- Decrease risk 2º infection
- Decrease risk of stromal melting
- Rolled borders of epithelium
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61TREATMENTTrophic Epithelial Defect
- Protect ocular surface
- Non preserved lubricants
- Therapeutic contact lens
- Gentle debridement
- Amniotic membrane
- Tarsorrhaphy
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64ENDOTHELIITIS
- Inflammatory reaction of endothelium
- Corneal stromal edema without infiltrate
(disciform, diffuse, linear) - KP, Stromal/epithelial edema, iritis
- Responds to steroids
65REACTIVATION HSV
- Hormonal changes
- Ultraviolet light
- Surgery of eye
- Systemic infection
- Latanoprost
66REACTIVATION HSV
- Stress
- Fever
- Immunosuppression
- Trauma (CL wear)
- 9.6 first year
- 36 _at_ 5 years
- 63 within 20 years
- HEDS 18 recurrence rate
67RECURRENT 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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69PROPHYLAXIS 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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74TREATMENTStromal Keratitis
- If corneal perforation
- Surgical adhesive
- Lamellar patch graft
- PKP
- Use of oral Acyclovir
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76VALACYCLOVIR(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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78FAMCICLOVIR
- MOA similar to Acyclovir
- Inhibits HSV DNA synthesis
- Rapidly absorbed from GI tract
- Intracellular 1/2 life is 10-20 times
longer - Lactose intolerance
79FAMCICLOVIR
- Dose 500mg bid-tid
- Side effects similar to Acyclovir
- More expensive cost
80CIDOFOVIRPENCICLOVIR
- Variation in chemical structure
- Inhibit DNA polymerase
- Less resistance
81VALTREX ANDFAMVIR
- Not more effective than Acyclovir
- Cost issue
- Compliance issue
82HEDS 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