VIRAL INFECTIONS OF CORNEA

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VIRAL INFECTIONS OF CORNEA
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Copy of lecture taken by Prof Sanjay
Shrivastavafor Junior Final M.B.B.S students
of Gandhi Medical College Bhopal (M.P.) India
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Types
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Superficial Viral Keratitis
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Causes

• Causes
• Herpes Zoster
• Adenoviruses
• Chlamydia Trachomatis
• Inclusion Conjunctivitis
• Rare causes Mumps, Measles, Vaccinia, Infectious
  mononucleosis, Secondary to Molluscum Contagiosum
  and Warts

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Clinical Manifestations
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I. Punctate Epithelial Erosion

• This is most common manifestation of viral
  superficial infections
• Minute epithelial defects, staining with
  Fluorescein
• Acute manifestation associated with
  conjunctivitis. There is pain, photophobia and
  lacrimation
• Usually characterized by recurrences of fresh
  erosions occurring in crops after subsidence of
  initial keratitis

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Superficial Punctate Keratitis
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Differential Diagnosis

• Bacterial due to staphylococcal toxins
  (associated with blepharitis and conjunctivitis)
• Chemical
• General febrile illness due to adenovirus may
  also be associated with this clinical picture

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Treatment

• Lubricating (artificial tear) drops
• Chloramphenicol eye drops to prevent secondary
  bacterial infection

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II. Punctate Epithelial Keratitis(Superficial
Punctate Keratitis)

• Both eyes are affected
• Prolonged course for months or years
• Affects deeper layer, sometimes opacities extends
  to Bowmans membrane and superficial stroma
  (Punctate sub-epithelial keratitis)

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Clinical Picture

• Superficial opacities , grey dots, slightly
  raised above in the central cornea, they do not
  take fluorescein stain, but stain with Rose
  Bengal
• Combined picture of epithelial and sub-epithelial
  lesions may be present, as in epidemic
  keratoconjunctivitis, pharyngo-conjunctival
  fever, herpes, vaccinia etc, it may also occur
  without known cause as in Thygeson superficial
  keratitis

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Treatment

• Lubricating (artificial tear) drops
• Steroids may be used under supervision (required
  for long time)

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Herpes Simplex
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Herpes Simplex

• The herpes simplex virus is essentially human
  pathogen that can cause asymptomatic infection as
  well as active disease in variety of organs
• Two antigenic types are known
• a. Herpes Simplex Virus (HSV) 1
• b. Herpes Simplex Virus (HSV) 2

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Antigenic types

• HSV 1 usually causes oropharyngeal disease and
• HSV 2 usually involves genital areas
• Typically ocular disease is caused by type 1
  rather than type 2.
• Humans are the only natural reservoir of HSV.
  Close personal contact is necessary for the
  spread of virus

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HSV infection

• Primary infection rarely causes clinical
  manifestations. Recurrent infection is more
  common from Trigeminal ganglion in most of the
  cases
• Factors implicated in the activation of recurrent
  HSV ocular disease (Reactivation of latent
  infection) immune system deficiency, sunlight,
  heat, trauma (including surgery), abnormal body
  temperature, menstruation, other infectious
  diseases, emotional stress

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Ocular manifestations

• Blepharitis
• Conjunctivitis
• Keratitis
• Iridocyclitis

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Corneal involvement

• Epithelial
• Corneal vesicles
• Dendritic ulcer
• Geographical ulcer
• Marginal ulcer
• II. Neurotrophic Keratopathy

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Corneal Involvement

• III Stromal
• Necrotizing stromal keratitis
• Interstitial immune mediated (Non-necrotizing)
  Keratitis
• IV Endothelial Disciform, Diffuse and Linear
• Primary lesion usually seen in children,
  manifest itself as follicular keratoconjunctiviti
  s
• In recurrent form only cornea is involved

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Corneal Lesions
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I. Superficial Punctate Keratitis

• Superficial Punctate Keratitis Numerous minute
  whitish plaques arranged in rows or groups. These
  lesions desquamate forming erosions which heals
  rapidly without leaving opacities
• Symptoms Pain, irritation, blepharospasm, and
  photophobia
• Recurrence of fresh crops

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Epithelial Keratitis
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Corneal Lesions

• Desquamation leaves minute shallow clear
  facets, they are not vascularized, arranged in
  groups, they have crenated edges. Several lesions
  may coalesce and epithelial filaments are present
  
• Cornea is relatively insensitive

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II Dendritic Ulcer

• Dendritic Ulcer occurs in severe form of
  disease. Lesions coalesce and spread in all
  directions to form large shallow ulcer with
  crenated edges. Grey striae extending in one or
  more directions, increasing in length, sending
  knobbed lateral branches Dendritic figure form
• This appearance is seen exclusively in this
  condition and is pathognomonic

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Dendritic Ulcer

• Surface over infiltration breaks leaving
  extremely irritating chronic ulcer
• Lesions persists for weeks or months sending out
  fresh branches which remains superficial
• Only 1 or 2 lesions may take fluorescein stain at
  any given time
• Fresh spots continue to form and disease has
  tendency to recur
• A large confluent ulcer may form

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Dendritic Keratitis
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Dendritic Keratitis
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Dendritic Ulcer

• In the mean time stroma may be implicated and a
  disciform keratitis develops due to immunological
  reaction
• Iritis usually accompanies severe form of
  herpetic keratitis
• In very severe form of disease hypopyon may
  develop , from which virus may be isolated

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Herpes Simplex Keratitis
Geographical Keratitis
Dendritic Keratitis
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Herpes Simplex Keratitis
Stromal necrosis leading to Descemetocele
Marginal Keratitis
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Dendritic Ulcer

• Diagnosis
• Immunoflurescence test,
• Culture of epithelial scrapping or
• Tissue biopsy

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Treatment

• Topical and Systemic Antivirals
• Topical and Systemic Steroids
• Supportive therapy (artificial tears)
• Cycloplegics

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Local Antiviral Drugs

• Idoxuridine 5 drops used 5 times a day
• Trifluridine 1 drops used 4 times a day
• Acyclovir ointment 3 used 5 times a day
• Vidarabine ointment 3 used 5 times a day
• ORAL Acyclovir 400 / 800 mgm tab

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Treatment of Epithelial Keratitis

• Topical antivirals Antibiotics (antiviral is
  usually required for 15 days)
• Lubricating (Artificial tear) eye drops
• Cycloplegic drops
• Debridement of edges of Dendritic ulcer with
  moist cotton tipped applicator
• Corticosteroids are contraindicated

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Treatment of stromal disease (and also of
endothelial and iridocyclitis)

• Treated with topical steroid and antiviral drugs

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Indications of systemic Acyclovir

• Non-responsive immune compromised primary HSV
  infected case especially with iridocyclitis
• Significant primary HSV infection
• Immune compromised patient (Moderate to severe)
  with HSV infection
• Infectious epithelial keratitis in adults
• HSV iridocyclitis
• Recurrent epithelial infection Dose 200 400
  mgm twice daily for long term (6 months)
• Operated cases of penetrating Keratoplasty to
  prevent recurrence (400 mgm bid)

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Adjuvant therapy

• Therapeutic contact lens
• Collagenase inhibitors
• Tarsorrhaphy
• Conjunctival Flap
• Cyanoacrylate glue in cases of perforated ulcer
• Lamellar or penetrating keratoplasty

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Herpes Zoster Ophthalmicus
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HZO

• Caused by Varicella Zoster virus which belongs to
  herpes virus group
• In developed world approximately 95 of the
  population shows evidence of prior VZV infection
• Varicella is highly contagious exanthematous
  illness manifested by prodromal symptoms and
  diffuse vesicular rash

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HZO

• Following acute infection VZV travels through
  peripheral nerves axons to dorsal root where it
  becomes latent
• Virus is endemic and becomes epidemic during late
  winter and early spring
• Varicella manifestations cause significant
  morbidity and mortality in immuno-suppressed
  hosts

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HZO

• Herpes zoster occurs due to reactivation of VZV,
  upon reactivation virus replicates in the cells
  of dorsal root ganglion and travel to skin and
  mucous membrane via axons. Cranial nerve
  involvement (Trigeminal) occurs in approximately
  13 -20 of cases
• Presence of vesicles at the side of the nose
  results from involvement of nasociliary nerve
  which supplies this area and intra-ocular
  structures (Hutchinsons sign)

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HZO

• Ocular involvement is seen in about 50 of cases
• Corneal involvement occurs in about 2/3rd of
  patients with ocular disease in acute HZO

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Herpes Zoster Ophthalmicus (HZO)

• PATHOGENESIS
• After infection during childhood or youth, the
  virus becomes dormant usually in Gasserian
  Ganglion.
• In case of Zoster Ophthalmicus it appears later
  particularly when cellular immunity is depressed,
  particularly in elder persons

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HZO

• Virus travels down along one or more branches of
  ophthalmic division (which is branch of Vth
  nerve, trigeminal nerve)
• The area of distribution of branches of
  ophthalmic division of V th nerve is marked by
  rows of vesicular eruptions or scars left by
  vesicles
• Branches of ophthalmic nerve involved are
  -supraorbital, supratrochlear and infratrochlear
  frequently nasal branch and sometimes
  infraorbital branch

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HZO

• Condition is usually unilateral, but it may be
  bilateral in immuno-compromised cases

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Symptoms

• General fever, malaise, eruptions along the
  distribution of involved nerve, preceded by
  severe neuralgic pain. It sometimes ceases after
  outbreak of the eruptions, but may persists for
  months or years
• Skin of affected area becomes edematous and red
• Differential diagnosis erysipelas but
  distribution along involved nerve branches
  differentiate

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Herpes Zoster Ophthalmicus
Clinical photographs showing distribution of
rashes
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Symptoms

• Vesicles may suppurate , bleed and may cause
  small scars (depressed)
• Eruptive stage lasts for about 6 weeks followed
  by depressed sensation of affected scarred area
• Ocular complications arise when eruptive stage is
  subsiding. The ocular complication are usually
  overlooked during acute stage due to difficulty
  in examination of eye.

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Symptoms

• The ocular complications are associated with
  involvement of nasociliary branch which is
  characterized by presence of vesicles on the tip
  of nose

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Ocular Manifestations

• Lid edema
• Numerous minute white round spots in the
  epithelium, soon involving the stroma, seen as
  coarse sub-epithelial punctate keratitis
• Discoid lesions are termed nummular keratitis
  (hardly distinguishable from other forms of viral
  keratitis)
• Sometimes infiltration involves stroma, as
  diffuse stromal inflammation, with iridocyclitis

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Corneal changes in HZO

• Punctate epithelial keratitis
• Pseudodendritic keratitis
• Anterior stromal keratitis
• Kerato-uveitis / endothelitis
• Serpiginous ulceration
• Sclerokeratitis
• Corneal mucous plaques
• Disciform keratitis

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Corneal involvement in HZO
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Ocular involvement in HZO
Scleritis Keratitis
Skin scarring keratouveitis
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Corneal changes in HZO

• Neurotrophic keratopathy
• Exposure keratopathy
• Interstitial keratitis / lipid keratopathy
• Permanent corneal edema

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Ocular Manifestations

• Cornea is usually anaesthetized
• Scleritis leaving grey scarred areas on sclera
• Iridocyclitis leaving sectoral iris atrophy
• Intra-ocular tension low initially, increases
  later
• Corneal anaesthesia persists for long

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Ocular involvement in HZO
Scleritis
Keratitis
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Ocular involvement in HZO
Keratitis
Distribution of Skin lesions
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Ocular Manifestations

• There may be associated paralysis of the
  oculo-motor nerve, abducens and facial nerve
  which usually passes off in 6 weeks
• Complications retinal necrosis (after 5 days to
  3 months) and optic neuritis
• Neurological manifestations acute neuralgia,
  post herpetic neuralgia, encephalitis, myelitis/
  encephalomyelitis, segmental motor weakness,
  cranial neuropathies and delayed cerebral
  vasculitis

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Treatment

• Acyclovir 800 mgms five times a day for 10 days
  (it reduces the period of viral shedding ,
  accelerate the time for healing by 50, decreases
  the pain and reduces occurrence of fresh lesions.
  It reduces the chance of post herpetic neuralgia)
  
• Systemic Acyclovir should be given early
  preferably within 4 days of beginning of rashes
• Alternatively oral Famciclovir, 250 mgms thrice
  daily for 7 days

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Treatment

• 2. Oral strong analgesics and non-steroidal
  anti-inflammatory drugs
• 3. Maintenance of hygienic condition to prevent
  secondary infection. Topical antiviral
  (acyclovir) and antibiotic ointment on skin
  lesions
• 4. Topical antibiotic drops and ointment in the
  eye during acute phase
• 5. Scleritis is treated with topical steroid and
  antiviral to reduce ischemia and scarring

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Treatment

• 6. Systemic steroids are indicated in
• a. progressive proptosis
• b. 3rd nerve palsy
• c. optic neuritis (to take care of occlusive
  vasculitis)
• 7. Artificial tears for dryness of ocular surface
  
• 8. Neurotrophic ulcer by lateral tarsorrhaphy
• 9. Penetrating keratoplasty in cases of dense
  scarring and lipoidal deposits in central cornea