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All About Herpes Simplex SECO International 2015

Course #137 Daryl F. Mann, O.D.

President SouthEast Eye Specialists, PLLC

Chattanooga & Knoxville, TN

HERPES SIMPLEX VIRUS (HSV)

•  500,000 people in US with HSV-related ocular disease1

•  20,000 new episodes & 28,000 reactivations yearly1

•  Leading cause of corneal blindness in US2; 2nd in World

1Wang JC. Keratitis, Herpes Simplex. Emedicine. Accessed online from: http://emedicine.medscape.com/article /1194268-overview.

2Liesegang,TJ, Melton LJ, 3rd, Daly PJ, Ilstrup DM. Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950-1982. Arch Ophthalmol 1989;107:1155-9.

Herpetic Simplex Virus

•  HSV is a double-stranded DNA virus that causes disease after direct contact with skin or mucosal membranes by virus-laden secretions from an infected host.1

•  HSV Type 1 •  HSV Type 2

1Welder JD, Kitzmann AS, Wagonger MD. Herpes Simplex Keratitis. Accessed online from http://webeye.ophth.uiowa.edu.

Herpetic Simplex Virus

•  HSV Type 1 – Above the waist – Bimodal onset – Nearly 100% of adults > age 60 harbor HSV @

autopsy1 •  HSV Type 2

– Below the waist – STD

1AAO Basic and Clinical Science Course, External Disease and Cornea 2010-2011

Primary HSV Infection

•  More common in childhood •  Non-ocular

–  Flu-like symptoms –  Self-limited

•  Ocular –  Follicular conjunctivitis OU –  Periocular HSV blisters on

lids –  Self-limited

Recurrent Ocular HSV Infection

•  Once in tissue, virus spreads from site of the initial infection to the neuronal cell bodies

•  Can lie dormant for years •  Most ocular HSV infections are

secondary •  Trigger Mechanism

–  Stress, illness, menses, immunosuppression, sun exposure, fever, trauma.

•  Past ocular history most significant risk factor

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Recurrent Ocular HSV Infection

•  Blepharitis •  Conjunctivitis •  Scleritis •  Anterior Uveitis •  Necrotizing Retinitis •  Choroiditis •  Optic Neuritis

HSV-Keratitis: Clinical Presentation

•  Epithelial Dendrite •  Geographical dendrite •  Stromal

–  Non-necrotizing & necrotizing

•  Endothelial (disciform) •  Metaherpetic •  Most cases are (> 90%) unilateral1

1Welder JD, Kitzmann AS, Wagonger MD. Herpes Simplex Keratitis. Accessed online from http://webeye.ophth.uiowa.edu.

Recurrent HSV-K Infection

•  Epithelial keratitis –  75% have epithelial

involvement –  Invariably involves

active viral proliferation

Limbal HSV-K

Limbal HSV Recurrent HSV-K Infection

•  Stromal keratitis –  25% have stromal

involvement –  Non-necrotizing –  Necrotizing –  Disciform (endothelial)

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Disciform HSV-K Non-necrotizing Stromal HSV-K

Necrotizing Stromal HSV-K Geographic HSK

Metaherpetic/Neurotrophic HSV-K HSV-K: Clinical Diagnosis

•  Tests –  Tzanck (Giemsa) –  Viral culture –  Viral antigen assay –  PCR

•  Clinical Diagnosis –  History & symptoms –  Clinical appearance

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Epithelial HSV-K Epithelial HSV-K

HSV-K: Clinical Diagnosis

•  Vital stains –  Rose Bengal

Rose Bengal

HSK: Clinical Diagnosis

•  Vital stains – Rose Bengal – Fluorescein

Pseudo-dendrites

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HSK: Clinical Diagnosis

•  History & Symptoms •  Clinical appearance •  Vital stains

–  Rose Bengal –  Fluorescein

•  Corneal hypesthesia –  Cochet-Bonnet

aethesiometry

HSK: Clinical Diagnosis

•  History & Symptoms •  Clinical appearance •  Vital stains

–  Rose Bengal –  Fluorescein

•  Corneal hypoesthesia •  Level of Suspicion •  Response to treatment

& non-treatment

Management HSV-K

•  Topical Antivirals – Zirgan (ganciclovir ophthalmic gel) 0.15% – Viroptic (trifluridine ophthalmic)

•  Oral Antivirals – Acyclovir (Zovirax) – Valacyclovir (Valtrex) – Famciclovir (Famvir)

•  Topical Corticosteroids

Guiding Principle for treatment of HSV-K1

•  Prior to onset of immune-mediated disease, control and elimination of epithelial manifestations is the highest priority.

•  However, once immune-mediated disease has been established, management of stromal or endothelial manifestations, with their potential for irreversible visual impairment, has higher priority than control of epithelial disease.

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Zirgan® (ganciclovir ophthalmic gel) 0.15%

•  FDA approved ZIRGAN for sale on Sept 15, 2009...Bausch & Lomb purchased the U.S. rights from Sirion

•  The recommended dosing regimen for Zirgan is 1 drop in the affected eye 5 times per day (approximately every 3 hours while awake) until the corneal ulcer heals, and then 1 drop 3 times per day for 7 days.

Please see full Zirgan® Webinar Deck PH3234 07/10 © 2010 Bausch & Lomb Incorporated Zirgan® is a trademark of Laboratories Théa Corporation licensed by Bausch & Lomb Incorporated All other product/brand names are trademarks of their respective owners.

Oral Antivirals for HSV

•  Acyclovir (Zovirax) –  200 mg & 400 mg –  400 mg 5 X day x 14-21 days

•  Valacyclovir (Valtrex) –  Pro drug with 3-4x conc; 500 mg & 1 gm –  500 gms 3 X per day x 14-21 days

•  Famciclovir (Famvir) –  125 mg, 250 mg & 500 mg –  1.0 gms per day

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HEDS I Outcomes

•  Steroids are helpful in tx of stromal disease •  No apparent benefit of adding acyclovir to

treatment regimen of steroid and anti-viral for stromal disease

•  Possible benefit of adding acyclovir in tx of HSV iritis to tx regimen of Viroptic & steroid

HEDS II Outcomes

•  No benefit of adding oral acyclovir to tx regimen of topical trifluridine in the prevention of HSV stromal keratitis

•  Oral acyclovir (400 mg bid) reduced recurrent rate 41% of any recurrence and 50% of stromal recurrence

•  External factors???

Treatment Plan HSV-K

•  Epithelial – Zirgan: 5 gtts/day an taper –OR- – Viroptic: 9 gtts/day and taper

– Acyclovir: 2 gms/day and taper? -OR- – Valtrex: 1.5 gms/day and taper?

Treatment Plan HSV-K

•  Epithelial –  Zirgan: 5 gtts/day and taper –  Viroptic: 9 gtts/day and taper –  Acyclovir: 2 gms/day and taper –  Valtrex: 1.5 gms/day and taper

•  Stromal w/ Epithelial –  Same as above until epithelium intact or concomitant

addition of corticosteroid •  Stromal w/o Epithelial

–  Oral as above –  Corticosteroid q 1-3 hours initially (slow, slow taper)

Disciform HSV-K Antiviral prophylaxis1 Acyclovir 400 mg PO BID or Valacyclovir 500 mg PO QD

•  HSV epithelial disease –  Initial episode – no prophylaxis therapy –  1 or more recurrent episodes = oral therapy x 1 yr

•  HSV stromal keratitis –  Initial episode (uncomplicated) = oral therapy x 1 yr –  Initial episode (complicated) = oral therapy x 2 yrs – Chronic disease = oral therapy 2 yrs to indefinite

1 1Welder JD, Kitzmann AS, Wagonger MD. Herpes Simplex Keratitis. Accessed online from http://

webeye.ophth.uiowa.edu.

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Case Presentation HSV-K

•  28 yo Male c/o of irritation in RE while working on his mechanics job

•  + hx of oral fever blisters •  SLEx

– Unilateral conjunctival injection – Central dendritic epithelial defect

•  + RB and + FL staining –  ? Reduced corneal sensation

Case Presentation HSV-K: Day 1

Case Presentation HSV-K

•  Diagnosed initial episode of epithelial HSV-K •  Initiated therapy of Zirgan 5 X day and Valtrex

500 mg PO TID (#60) •  RTC 2 days

HSV-K: Day 3

Case Presentation HSV-K

•  Patient is symptomatically improved and compliant with meds

•  Continue Valtrex 500 mg PO TID and reduce Zirgan to 3 X day

•  RTC 2 days

HSK: Day 5

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Case Presentation HSV-K

•  Patient is symptomatically improved and compliant with meds

•  Continue Valtrex 500 mg PO TID and continue Zirgan TID

•  RTC 2 days

HSK: Day 7

•  Discontinue Zirgan. Finish Rx of Valtrex. Follow up with primary care optometrist 2 weeks.

Case Presentation

•  44 y/o Female c/o blurred vision and red eye for 3 weeks

•  Treated with Tobradex by doctor for two weeks with no improvement

•  + hx of oral fever blisters •  VA 2/400 •  SLEx

–  Large geographic area of epithelial loss –  Decreased corneal sensation

Case Presentation

•  36 yo WM with hx of recurrent HSK •  Most recent episode treated with Viroptic

over 2 week period on tapering scheduled •  HSV-K recurred and Viroptic was restarted •  Referred after 4 weeks of therapy

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Management Metaherpetic HSK

•  Discontinued Viroptic •  Placed on Valtrex 500 mg TID and quickly

tapered to 500 mg QD maintenance •  Minimal debridement of necrotic epithelium •  Lubricants •  Can use TSCL

Case Presentation

•  21 y/o male with hx of recurrent HSK reports decreased vision and redness for 1 week

•  VA 20/80 •  SLEx

– Active stromal HSV-K at edge of corneal scar – + FL – Decreased corneal sensation

Recurrent HSK

In Summary

•  Always think HSV infection in unilateral red eye

•  Follow standard of care in treating HSK THANK YOU