Dr Doug Parker gave a presentation on herpetic corneal disease. He discussed how herpes simplex virus (HSV) and varicella zoster virus (VZV) can infect the cornea and cause disease. HSV typically causes epithelial dendritic ulcers or stromal keratitis, while VZV causes herpes zoster ophthalmicus. Treatment involves antiviral medications, with steroids also used for stromal inflammation. Reduced corneal sensation is a sign of previous herpetic disease and risks neurotrophic ulcers.

1. CORNEAS ON THE COAST
SPOTLIGHT ON HERPETIC CORNEAL DISEASE
Dr Doug Parker PhD FRANZCO
Cornea, Cataract & Refractive Specialist
Gosford&Wyong Eye Surgery
Eye Associates, Macquarie St, Sydney
CentralCoast Optometrist Conference, 2 March 2014

2. Outline
 Herpetic corneal disease
 HSV vVZV
 Diagnosis
 Treatment
 Prophylaxis
 MCQs
 Acknowledgements
 Professor John Dart, Moorfields Eye Hospital, London
 www.aao.org/medialibrary

3. Herpetic Corneal Infections
 HSV-1 (Herpes simplex)
 Cold sores, keratitis
 HSV-2
 Genital herpes
 VZV (Varicella zoster)
 Chicken pox, shingles, HZO
 All neurotrophic sensory
nerve ganglia
 Trigeminal

4. Herpes Simplex Keratitis
 Primary HSV infection by
direct contact
 May get a
blepharoconjunctivitis
(follicular)
 Latency
 Utilises cellular enzymes for
replication  host cell death
 Loss of ganglion cells 
reduced corneal sensation
 Basic forms:
 Epithelial
 Stromal
 Endothelial

5. Herpes Simplex Keratitis
 Challenges:
 Making the diagnosis
 Recognising recurrences and judging
activity
 Treatment and prophylaxis
 Epithelial keratitis
 Actively replicating virus
 Dendritic ulcer  may leave a ghost
dendrite
 Geographic ulcer
 Marginal keratitis
 Metaherpetic (trophic) ulcer

6. Herpes Simplex Keratitis
 Stromal and endothelial keratitis
 Immune-mediated response to non-replicating virus (severe
forms may be live)
 Focal, multifocal or diffuse stromal opacities
 May be associated oedema and AC reaction
 With new vessels  “interstitial keratitis”
 May leak lipid
 Necrotisingkeratitis
 Due to live particles (multiple recurrences, HSV-2)
 Must be distinguished from microbial keratitis
 May cause melting and perforation
 Associated uveitis and trabeculitis glaucoma
 Localised endothelial dysfunction  “disciformkeratitis”
 Pseudoguttae and Descemet’s membrane folds
 Keratouveitis
 Immune-mediated
 Synechiae, cataracts
and glaucoma

7. Herpes Simplex Keratitis
 Diagnosis
 Clinical
 Lab tests (no use in stromalkeratitis)
 Culture, PCR, serology
 Differential: AK, RCES, healed ED in OSD, HZ
 Long-term complications
 Recurrence  inflammation and scarring
 Reduced sensation
 A sensitive sign of previous HSK
 Poor tear production, decreased growth factors
 Leads to persistent epithelial defects and neurotrophic
ulcers

8. Triggers for recurrence of HSK
Ophthalmic Systemic
 Contact lens wear
 Eye injury
 Corneal grafting
 Laser eye surgery
 Cataract surgery
 Intravitreal injections
 Topical prostaglandin
analogs
 Stress
 Systemic infection/fever
 Sunlight exposure
 Menstruation
 Genetic factors

9. Herpes Simplex Keratitis
 Treatment
 Herpetic Eye Disease Study (HEDS)
 Epithelial disease
 Debridement (also use for PCR or culture)
 Monotherapy with topical antiviral (Aciclovir,
Ganciclovir,Trifluridine)
 No added benefit of oral antiviral but may be useful
in kids or allergic patients
 Normal dendrites heal in 1-3 weeks
 If not  think toxicity, resistance or wrong diagnosis!

10. Herpes Simplex Keratitis
 Treatment
 Stromal disease
 Mainstay is topical steroids
 Shorten duration of disciform and non-necrotisingstromal disease
 Dosing based on severity of inflammation
 Taper to prevent rebound
 Always under antiviral cover
 Simultaneous oral antiviral prophylaxis reduces risk of HSV
reactivation at ganglion level
 Prophylaxis
 Topical antivirals are toxic with prolonged use
 Systemic aciclovir reduces recurrence of stromalkeratitis by 50%
(HEDS-APT)
 Aciclovir 400 mg bd
 Can also useValaciclovir 500 mg bd, or Famciclovir 250 mg bd

11. Herpes Zoster Ophthalmicus (HZO)
 Varicella-zoster virus (VZV)
 Primary infection is chicken pox
 Becomes latent in multiple ganglia
 Reactivates as shingles
 HZO in 10-20% cases
 Exact triggers unknown but decreased cellular
immunity is common
 Diagnosis:
 Fever, malaise, chills
 Pain or tingling in dermatome
 Maculopapular rash  vesicles  crusting
 May have eyelid oedema
 Hutchinson’s sign indicates involvement of nasociliary
nerve (and eye)
 Can affect any part of the eye

12. Herpes Zoster Ophthalmicus
 Acute keratitis
 May occur up to 1 month after rash starts
 Punctatekeratitis and pseudodendrites (lack terminal
bulbs)
 Does not respond to topical antivirals
 Nummular keratitis (coin-shaped lesions) are an
immune-mediated stromal reaction to antigen
 Recurrent keratitis
 Mucous plaques
 Disciformkeratitis (as seen in HSK)
 Interstitial keratitis with lipid exudation
 Long-term complications
 Profound loss of corneal sensation neurotrophic
ulcer
 Smoldering stromalkeratitis (haze, scarring, reduced
vision)
 Neuralgia (PHN)

13. Herpes Zoster Ophthalmicus
 Treatment
 Topical antivirals have no role
 Oral antivirals begun early can reduce
severity of disease and long-term
complications (e.g neuralgia)
 Aciclovir 800 mg 5 times per day, or Famvir
500 mg tds
 Topical steroids may be necessary for
stromal inflammation, but difficult to wean
 Need to support the neurotrophic cornea
 Lubricants, punctal occlusion, bandage
contact lenses, tarsorrhaphy, conjunctival
flaps all have a role
 Nerve growth factor
 Zostavax

14. Herpetic corneal disease
 Key points
 HSV andVZV cause distinctive clinical pictures
 Each layer of the cornea may be affected with
different manifestations
 Never start topical steroid in suspected herpes
simplex keratitis without antiviral cover
 Reduced corneal sensation can be a useful sign of
previous disease
 Protect the neurotrophic cornea

15. MCQ #1
 Which of the following is a sensitive sign of
previous herpetic keratitis?
A. Prominent corneal nerves
B. Descemet’s membrane folds
C. Reduced corneal sensation
D. Corneal vascularisation

16. MCQ #2
 Herpes simplex keratitis and herpes zoster
ophthalmicus have the following in common,
except:
A. They are both caused by a double-stranded DNA
virus
B. There is a role for topical antiviral treatment in
both cases
C. Both can lead to neurotrophic ulceration
D. There is a role for topical steroid in certain cases
of both conditions

17. MCQ #3
 Which of the following would be the best first
step in managing a dendritic corneal ulcer in
the absence of any stromal inflammation?
A. Commence a topical antiviral agent alone
B. Commence a topical antiviral agent and a topical
steroid
C. Commence lubricants and review in 1 week
D. Commence a topical steroid alone

18. MCQ #1
 Which of the following is a sensitive sign of
previous herpetic keratitis?
A. Prominent corneal nerves
B. Descemet’s membrane folds
C. Reduced corneal sensation
D. Corneal vascularisation

19. MCQ #2
 Herpes simplex keratitis and herpes zoster
ophthalmicus have the following in common,
except:
A. They are both caused by a double-stranded DNA
virus
B. There is a role for topical antiviral treatment in
both cases
C. Both can lead to neurotrophic ulceration
D. There is a role for topical steroid in certain cases
of both conditions

20. MCQ #3
 Which of the following would be the best first
step in managing a dendritic corneal ulcer in
the absence of any stromal inflammation?
A. Commence a topical antiviral agent alone
B. Commence a topical antiviral agent and a topical
steroid
C. Commence lubricants and review in 1 week
D. Commence a topical steroid alone