Herpes simplex keratitis & herpes zoster opthalmicus

1. HSV Keratitis and Herpes Zoster
Ophthalmicus
Presenter : Dr.Rasika Thakur
Moderator : Dr. Vishram Sangit

2. Case presentation
HSV keratitis
Introduction
Pathology and Clinical features
Treatment
Herpes zoster ophthalmicus
Introduction
Pathology and Clinical features
Treatment
Clinical pattern of Herpes simplex keratitis: A case
series

3. Case scenario 1
 Mr X, 24/M
Came to us on 29/12/2011 with c/o redness and
watering of RE since 2 months
BCVA-RE:FC1/2 m,N36,LE:6/6,N6
Patient had taken treatment elsewhere ,but found no
relief with
Eye drop tobramycin
Eye drop moxifloxacin and ketorolac
Eye ointment neosporin
• Recurrent attack of HSV keratitis

4. 29/12/2011

5. 2/1/2012

6. 5/1/2012 13/1/2012

7. 27/1/2012 1/3/2012

8. 13/9/2012

9. 26/10/2012

10. 30/11/2012

11. Case scenario ii
Patient Mr.XYZ, 65/M
C/o redness and watering since 7 days

12. 18/3/2014
Fortified cefazolin half hourly
Ciplox eyedrop half hourly
Atropin eyedrop TDS

13. 21/3/2014

14. 28/3/2014

15. 2/4/2014
Impression -HSV keratitis with bacterial keratitis

16. 21/4/2014

17. Mixed corneal ulcer

18. Introduction
Herpes simplex is the leading cause of infectious corneal
blindness*
While not all humans manifest herpes infection, more
than 90% carry the latent virus
HSV keratitis is Herpes simplex viral infection of the
cornea
*Liedtke W., Opalka B., Zimmermann C.W., Lignitz E.: Age distribution of latent
herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue. J
Neurol Sci 1993; 116:6-11

19. Herpes simplex virus

20. Life cycle of HSV

21. Primary HSV infection
Blepharoconjunctivitis
Follicular conjunctivitis
Lid vesicles and conjunctival dendrites
Kaposi’s varicelliform eruption
Severe morbidity -multi-system failure or bacterial
superinfection
Darougar S., Hunter P.A., Viswalingam M., et al: Acute follicular conjunctivitis and
keratoconjunctivitis due to herpes simplex virus in London. Br J Ophthalmol 1978; 62:843-849

22. Clinical Importance
Human herpesviruses have in common a state called
“latency” where the virus remains dormant in cells and
periodically reactivates
Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) have an
affinity for the sensory ganglion cells and are therefore
called neurotrophic viruses

23. Recurrent HSV Infections
Multiple factors are thought to cause recurrence including
fever, sunlight, irradiation, menses, and emotional stress
Recurrent disease most commonly causes keratitis
HSVK is broadly classified into epithelial and
stromal/endothelial keratitis

24. Epithelial Keratitis
 Symptoms
FB sensation
photophobia
Redness
Blurred vision
Clinical features
Punctate epithelial keratitis
Classic arborizing dendritic epithelial ulcers with terminal bulbs
Geographic epithelial ulcer
Ciliary flush & conjunctival injection

25. Epithelial Keratitis
Dendritic ulcer
Geographic ulcer
Marginal keratitis
Metaherpetic (trophic) ulcer

26. Dendritic ulcer
Classic herpetic lesion
The borders are slightly raised,grayish, and stain with rose
bengal as they consist of infected cells that have
undergone acantholysis
On resolution, a dendrite-shaped scar, called a ghost
dendrite, may remain in the superficial stroma

27. Geographic ulcer
Immunocompromised, on topical steroids, or have
longstanding, untreated ulcers*
Dichotomous branching and terminal bulbs are seen at
the periphery
*Wilhelmus K.R., Coster D.J., Donovan H.C., et al: Prognosis indicators of herpetic keratitis.
Analysis of a five-year observation period after corneal ulceration. Arch Ophthalmol 1981; 99:1578-

28. Marginal keratitis
Located near the limbus
The presence of an epithelial defect and lack of corneal
sensation can aid in diagnosis
Significant stromal inflammation
They are more resistant to treatment and frequently
become trophic ulcers*
*Thygeson P.: Marginal herpes simplex keratitis simulating marginal catarrhal ulcer. Invest
Ophthalmol 1971; 10:1006

29. Treatment
Indications- ulcers larger than 4 mm, marginal ulcers, and
ulcers with underlying stromal inflammation
Topical antivirals
Gentle wiping débridement is a very good adjunct therapy
as infected cells are acantholytic and are poorly adherent
Wilhelmus K.R.: The treatment of herpes simplex virus epithelial keratitis. Trans
Am Ophthalmol Soc 2000; 98:505-532

30. Metaherpetic (trophic) ulcer
Trophic ulcer,if it arises de novo or a metaherpetic ulcer if
it follows a dendrite or geographic ulcer
Causes-
Toxicity from antiviral medications
Lack of neural-derived growth factors
Poor tear surfacing
Low-grade stromal inflammation
Neurotrophic ulcers start as roughened epithelium, which
then breaks down to produce an epithelial defect with
smooth margins

31. Treatment
Stop toxic medications
Tear film supplementation
Bandage contact lenses
Amniotic membrane
The cautious use of topical steroids may be necessary if
there is significant underlying inflammation

32. Stromal/Endothelial Keratitis
It is an immune-mediated response to nonreplicating viral
particles
All layers of the cornea are affected and may involve the
trabecular meshwork and iris
It is classified based on the predominant site and type of
involvement

33. Stromal/Endothelial Keratitis
Endotheliitis
Necrotizing keratitis
Immune stromal keratitis
Keratouveitis

34. Endotheliitis
Manifests as overlying stromal edema from endothelial
dysfunction
Longstanding stromal edema leads to permanent scarring
and is the major cause of decreased vision associated with
HSVK

35. Endotheliitis
Localized endotheliitis
Disc-shaped area of
corneal edema so called
disciform keratitis
There is minimal
stromal inflammation
and no epithelial
involvement
Diffuse and linear
endotheliitis
Accompanied by
trabeculitis with a
resulting elevated
intraocular pressure
Pseudo-guttae and
Descemet’s folds

36. Necrotizing keratitis
Inflammation in the cornea is due to a reaction to live
viral particles in the corneal stroma
Corneal melting and perforation
Associated with uveitis and trabeculitis that may lead to
recalcitrant glaucoma

37. Necrotizing keratitis

38. Immune stromal keratitis
Manifests as focal, multifocal, or diffuse stromal opacities
or an immune ring
Stromal edema and a mild anterior chamber reaction
It is called interstitial keratitis (IK) if accompanied by
vascularization

39. Keratouveitis
Uveitis is usually granulomatous with large “mutton-fat”
keratic precipitates on the endothelium
It can lead to significant morbidity from synechiae,
cataracts, and glaucoma
Unilateral uveitis associated with high intraocular
pressure is almost always caused by HSV

40. Treatment
The mainstay of treatment is topical steroids as they
decrease inflammation and therefore scarring
 Oral antivirals
Topical antivirals
Aggressive topical and systemic antivirals along with
steroids are necessary in necrotizing keratitis and focal
serous iritis

41. Diagnosis
Diagnostic testing is seldom needed in epithelial HSVK
because of its classic clinical features and is not useful in
stromal keratitis as there is usually no live virus present

42. Diagnosis
Culture
DNA Testing
 Fluorescent Antibody Testing
Tzanck Smear
 Serum Antibody Testing

43. HERPETIC EYE DISEASE STUDY (HEDS)
To assess the effect of adding steroids and acyclovir to
conventional therapy with trifluridine (TFT)
It was a prospective
 Randomized
Double-masked
Placebo-controlled
Multi-center study
Divided into six trials: three therapeutic, two preventive,
and one cohort

44. HEDS
Herpes Stromal Keratitis, Not on Steroids Trial
Compared with the placebo group, patients who received
prednisolone phosphate drops had faster resolution and
fewer treatment failures
Wilhelmus K.R., Gee L., Hauck W.W., et al: Herpetic Eye Disease Study. A controlled trial of
topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology 1994; 101:1883-
1895

45. HEDS
Herpes Stromal Keratitis, on Steroid Treatment
There was no apparent benefit to adding oral acyclovir to
topical corticosteroids and TFT. However, visual acuity
improved over 6 months in more patients in the acyclovir
group than in the placebo group
Barron B.A., Gee L., Hauck W.W., et al: Herpetic Eye Disease Study. A controlled trial of
oral acyclovir for herpes simplex stromal keratitis. Ophthalmology 1994; 101:1871-1882

46. HEDS
Herpes Simplex Virus Iridocyclitis, Receiving Topical
Steroids
The trial was stopped because of slow recruitment, but
treatment failures occurred at a higher rate in the placebo
group than in the acyclovir group, indicating a potential
benefit to adding oral acyclovir to the regimen of a topical
steroid and an antiviral
A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The
Herpetic Eye Disease Study Group. Arch Ophthalmol 1996; 114:1065-1072

47. HEDS
Herpes Simplex Virus Epithelial Keratitis Trial
In the treatment of acute HSV epithelial keratitis with
TFT, the addition of oral acyclovir offered no additional
benefit in preventing subsequent stromal keratitis or iritis

48. HEDS
Acyclovir Prevention Trial
Oral acyclovir reduced the risk of any form of recurrent
ocular herpes by 41% and stromal keratitis by 50%. The
risk of multiple recurrences decreased from 9% to 4%
Although there was no rebound increase in keratitis after
discontinuation of the acyclovir, the protection did not
persist once the acyclovir was discontinued
Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial
keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch
Ophthalmol 2000; 118:1030-1036

49. HEDS
Ocular HSV Recurrence Factor Study
No association was found between psychological or other
forms of stress and HSV recurrences
Previous episodes of epithelial keratitis were not a
predictor for future occurrences while previous, especially
multiple, episodes of stromal keratitis markedly increased
the probability of subsequent stromal keratitis
Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial
keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch
Ophthalmol 2000; 118:1030-1036

50. Limitations:
Many of the trials had inadequate recruitment or high
dropout rate
Oral acyclovir in the prevention trials was only used for 3
weeks
The steroid regimen was standardized and not tailored to
inflammation
TFT was used in both the study and placebo groups in all
the therapeutic trials

51. Current antivirals

52. Treatment
Steroids
1% prednisolone acetate or 0.1% dexamethasone is used
Surgery
Penetrating keratoplasty (PKP)
Conjunctival flap
Amniotic membrane (AMT)

53. FUTURE DIRECTIONS
Heat shock and glycoprotein subunit vaccines have shown
some promise in clinical trials in decreasing the number
and severity of recurrences of HSVK
while newer medications such as topical ganciclovir and
cidofovir may prove to be more effective and cause less
toxicity compared to current therapy*
Although monotherapy with interferon has not been
found to be effective, it increases the efficacy of acyclovir
and ganciclovir when given in combination**
*Colin J., Hoh H.B., Easty D.L., et al: Ganciclovir ophthalmic gel (Virgan; 0.15%) in the
treatment of herpes simplex keratitis. Cornea 1997; 16:393-399
**Wilhelmus K.R.: The treatment of herpes simplex virus epithelial keratitis. Trans Am
Ophthalmol Soc 2000; 98:505-532

54. Herpes zoster ophthalmicus

55. Introduction
Recurrent infection of varicella (chickenpox) in the
ophthalmic division of the trigeminal dermatome most
frequently affecting the nasociliary branch

56. Epidemiology and clinical Importance
Herpes zoster is a neurocutaneous disease caused by the
human herpes virus 3
Member of the herpes virus family (Herpesviridae) and
exclusively infects human or simian cells
The lifetime risk is 20–30%, and 50% of those living until
85 years of age will be affected*
Physical trauma and surgery have been correlated with the
development of zoster**
*Donahue J.G., Choo P.W., Manson J.E., Platt R.: The incidence of herpes zoster.
Arch Intern Med 1995; 155:1605-1609
**Evans R.W., Lee A.G.: Herpes zoster ophthalmicus, ophthalmoplegia and trauma.
Headache 2004; 44:286-288

57. Pathogenesis
In temperate climates,primary infection occurs before the
age of 10, manifests as chickenpox (varicella)
The virus then establishes a latent state in the sensory
ganglia
When there is diminished virus-specific and cell-mediated
immunity, the virus may reactivate and spread to the
corresponding dermatome along a spinal or cranial nerve
to generate the characteristic unilateral vesicular
exanthema

58. Pathogenesis
Begins with a prodrome of influenza-like illness -fatigue,
malaise, nausea and mild fever accompanied by
progressive pain and skin hyperesthesia
A diffuse erythematous or maculopapular rash then
appears over a single dermatome 3–5 days later
These eruptions progress to form clusters of papules and
clear vesicles, which then evolve through stages of
pustulation and crusting

59. Clinical manifestations

60. Clinical manifestations
Eyelids
Periorbital edema, pain, and hyperesthesia of the eyelid
skin
Secondary bacterial infection may occur following
dermal involvement*
Complications- scarring, cicatricial ectropion or
entropion, trichiasis, madarosis, poliosis, or even frank
loss of eyelid tissue
*Weiss R.: Herpes zoster following spinal surgery. Clin
Exp Dermatol 1989; 14:56-57

61. Clinical manifestations
Conjunctiva
papillary, pseudomembranous,
membranous, or follicular reaction
Episclera/Sclera
HZV episcleritis and scleritis may be either localized or
diffuse

62. Clinical manifestations
Cornea
Herpes zoster corneal disease can result in significant
vision loss.
Five basic clinical forms:
 Epithelial keratitis (acute or chronic)
 Nummular stromal keratitis
 Disciform keratitis
 Limbal vascular keratitis
 Neurotrophic keratitis,
with or without corneal perforation

63. Clinical manifestations
Uveitis-
 Nongranulomatous or granulomatous iridocyclitis
(anterior uveitis) with keratic precipitates and posterior
synechiae
Lens -Posterior subcapsular cataracts

64. Clinical manifestations
Anterior Chamber Angle and Glaucoma
Plugging of the trabecular meshwork due to the
presence of cellular debris, iris pigment, or hyphema
Pupillary-block glaucoma secondary to posterior
synechiae, with resultant iris bombe
Peripheral anterior synechiae
Chronic open-angle glaucoma-due to damage to the
trabecular meshwork
Chang S.D., De Luise V.P.: In: Tasman W., Jaeger E.A., ed. Duane’s
ophthalmology, Vol, 4. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.ch 20
(CD-ROM)

65. Clinical manifestations
Pupil
Horner’s syndrome
A tonic pupil secondary to herpes zoster ciliary
ganglionitis
Optic Nerve
Neuroretinitis, retrobulbar neuritis, or an ischemic
optic neuropathy
Herpes zoster optic neuritis may result from local
transmission of the virus within the orbit from the fifth
to the second cranial nerve

66. Clinical manifestations
Vitreous-Vitreous opacities, vitritis, and vitreous
hemorrhage
Retina –
Retinal hemorrhages
Retinal thrombophlebitis
Branch or central retinal artery occlusion
Retinal arteritis
Necrotizing retinopathy, necrotizing retinitis
Exudative or rhegmatogenous retinal detachment
 Ischemic perivasculitis

67. Clinical manifestations
Extraocular Muscles
Ophthalmoplegia 11–31%
Affect cranial nerves three, four, and six
Can also manifest as a myositis that may also lead to
ophthalmoplegia

68. Clinical manifestations
Postherpetic Neuralgia
Pain that continues following rash healing
Pain has three phases:
 Acute pain occurring within 30 days after rash onset
 Subacute herpetic neuralgia that persists beyond the
acute phase but resolves before 120 days
 Chronic PHN that persists 120 days or more after rash
onset

69. Herpes zoster ophthalmicus in acquired
imune deficiency syndrone (AIDS)
HZO is an important early clinical marker for AIDS,
especially in high-risk younger patients
Higher incidence, greater severity, and prolonged course
of corneal and uveitic involvement, as well as postherpetic
neuralgia
Treatment -prolonged treatment course of intravenous
acyclovir

70. Herpes zoster ophthalmicus in acquired
imune deficiency syndrome(AIDS)
Progressive outer retinal necrosis a distinct form of
necrotizing herpetic retinopathy
Characterized by multifocal, deep retinal lesions that
rapidly progress to confluence with minimal or no
intraocular inflammation, an absence of vascular
inflammation, and perivenular clearing of retinal
opacification

71. Diagnosis
The diagnosis of herpes zoster disease is based on clinical
findings
Direct detection of the virus and indirect serological
detection of specific antibodies
Cytologic examination of cutaneous vesicular scrapings
reveals multiple eosinophilic intranuclear inclusions
(Lipschutz bodies) and multinucleated giant cells (Tzanck
preparation)
Electron microscopy
VZV-DNA can also be directly detected in clinical
specimens using real-time PCR

72. Management
Systemic medication-
Oral acyclovir (800 mg, five times daily) for 7–10 days
Famciclovir (500 mg three times daily for 7 days)
Valacyclovir (1000 mg three times daily)
Cobo L.M., Foulks G.N., Liesegang T., et al: Oral acyclovir in the treatment of
acute herpes zoster ophthalmicus. Ophthalmology 1986; 9

73. Management of Ocular Manifestation
Palliative therapy including Burow’s solution, cool
compresses, mechanical cleansing of the involved skin,
and topical antibiotic ointment without steroid are helpful
in treating skin lesions
Débridement may also be helpful
Neurotrophic keratitis or the epithelial defects
-nonpreserved artificial tears, eye ointments, pressure
patching, or therapeutic soft contact lenses

74. Management of Ocular Manifestation
Tarsorrhaphy, conjunctival flap, or autologous
conjunctival transplantation
Steroids should not be used in cases of exposure or
neurotrophic keratitis because of the possibility of
keratolysis*
Topical cycloplegics
Aqueous suppressants and topical corticosteroids should
be used to treat HZO glaucoma
*Liesegang T.: Corneal complications from herpes zoster ophthalmicus.
Ophthalmology 1985; 92:316.

75. Management of Ocular Manifestation
Herpes zoster retinitis, optic neuritis, chorioretinitis,
acute retinal necrosis syndrome, and progressive outer
retinal necrosis are best treated with a combination of
systemic steroids and acyclovir i.v

76. Postherpetic Neuralgia treatment
Analgesics
Antidepressants (amitriptyline, desipramine,
clomipramine), carbamazepine, and phenytoin
Famciclovir and valacyclovir significantly reduce the
duration but not incidence
Steroids have no effect on PHN

77. Postherpetic Neuralgia treatment
Amitriptyline for 90 days reduced the incidence of pain at
6 months.
Trial of percutaneous electrical nerve stimulation (PENS)
in 50 patients suggested a decrease in pain incidence at 3
and 6 months when compared with famciclovir

78. Clinical pattern of Herpes simplex
keratitis: A case series
Dr Vishram Sangit1
Dr Suhas Haldipurkar1
,
Dr Maninder Setia1
,
Mr Anirban Paik1
1 Laxmi Eye Institute, Panvel, Maharashtra
FP-799; Electronic Poster no. 11

79. Purpose
To study the clinicoepidemiological pattern of Herpes
simplex keratitis in a tertiary eye hospital in western
Maharashtra

80. Results
41 eyes of 40 patients identified
All diagnoses – clinical
Mean age - 44.4 +/- 18.54 years
M:F – 27:13
Past history of similar episode- 20 patients
History of trauma in 7 patients
Only 2 out of 40 patients reported pain as the presenting complaint
Redness and blurring of vision was the most common symptom
reported by 38 patients
Mean duration of symptoms before presentation was 17.67 days
( range 2 to 90 days)

81. Clinical form of HSV Keratitis

82. Treatment protocols
Epithelial disease- Acyclovir ointment 5 times a day for 3
weeks
Stromal disease- Acyclovir ointment 5 times a day with
1% prednisolone acetate in tapering doses
Endothelitis- Intensive prednisolone acetate 1% with
systemic Acyclovir 400 mg 5 times a day

83. Treatment outcomes
All cases resolved on medical therapy
Mean duration to resolution for entire group was 34.18
+/- 15.85 days
Clinical
form
Epithelial Stromal Endothelitis Kerato-uveitis Mixed
Duration
(days)
18.6 39.06 29.66 35 35.91
Time to resolution in various forms of HSV keratitis

84. Mean time to resolution in various
forms of HSV keratitis ( days)

85. Recurrence pattern
Primary clinical form developing
recurrence during treatment
Clinical form of recurrence in HSV
keratitis (%)

86. Conclusions
Stromal form of HSV keratitis is the commonest presentation in our
series followed by mixed variety
HSV keratitis affects people in young and productive age group
Good response to medical therapy achieved in all forms
Resolution of stromal keratitis takes longest while epithelial keratitis
takes shortest time
Recurrences are common and clinical form of disease in recurrences
can be different from the original disease form

87. Thank you