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Aetiopathogenesis of
viral keratitis
CHAIRMAN: PROF. DR. MD. SAIFULLAH
DEPT OF CORNEA, NIO&H
MODERATOR: ASST PROF. DR.FARHAT JAHAN
DEPT OF CORNEA , NIO&H
PRESENTER: DR. SADIA YEASMIN SAKI
FCPS P-2 STUDENT, NIO&H
Viral keratitis
Herpes simplex
Varicella zoster
Adenovirus
Others(pox viridae, herpes viridae, papo viridae, picorna viridae, togaviridae)
Herpes simplex keratitis
are ubiquitous human pathogen capable of causing both asymptomatic infection & active
disease
Two types: HSV 1: oropharynx
HSV 2: genital organ
Ocular disease typically caused by type 1
Mode of infection:
Humans are the only natural reservoir
HSV 1: close contact, HSV 2: birth canal
HERPES SIMPLEX KERATITIS..
VIRAL STRUCTURE:
Double stranded DNA virus
Pathogenesis-latency
After peripheral entry into host & primary infection
HSV travel in a retrograde fashion to various ganglia( trigeminal, cervical, sympathetic)
Resides during the lifespan of the host
Once ganglionic presence has been established, active replication in neuron
Latency is established & presence of viral genome within the neuronal cell
Pathogenesis-Reactivation
LATS: latency –associated transcripts, a region of viral genome that is retained within host cell
During latency
Produced in large amount during reactivation from latency
Reactivation source
After primary infection
Subclinical reactivation: periodical HSV shedding
Clinical reactivation: fever
hormonal change
ultraviolet radiation
trauma
trigeminal injury
HSV keratitis..
Clinical manifestation
Congenital & neonatal
Primary infection
Recurrent infection
Congenital & neonatal ocular herpes
Most congenital cases are acquired: genital herpes in mother
during parturition
HSV-2 for 80% cases
Micropthalmia, retinal dysplasia, optic atrophy & chorioretinitis ( from intrauterine infection)
Ocular manifestation: periocular skin lesion
conjunctivitis
epithelial keratitis
stromal keratitis
cataract
Primary infection
After 6 months-maternal anti-HSV Ig G
Acute follicular conjunctivitis
Keratoconjunctivitis
Periocular lymphadenopathy
Periocular & eyelid skin vesicles
Diffuse punctate keartopathy
Corneal vesicles
Primary infection only confined to epithelium due to lack of
previous immunologic stimulus
Recurrent ocular herpes
Clinical manifestations:
blepharitis: vesicular lesion involving a focal area
conjunctivitis: recurrent follicular conjunctivitis
HSV keratitis
Iridocyclitis
HSV keratitis
Infectious epithelial keratitis
Symptoms: discomfort, redness, photophobia, watering, blurring of vision
Stellate lesion: swollen epithelial cell/ vesicle. earliest epithelial lesion
Dendritic ulcer: most common presentation
branching linear lesion, terminal bulbs ,swollen epithelial border
 Geographic ulcer: an enlarged dendritic ulcer that is no longer linear
Marginal ulcer: results from active viral disease,
proximal to limbus with accompanying blood vessel
Recurrent ocular herpes..
A) stellate lesion b)bed of dendritic ulcer with fluroscein stain
Recurrent ocular herpes..
C) margin of dendritic ulcer, rose Bengal stain d) geographic ulcer
Neurotrophic keratopathy
Impaired corneal innervation
Decreased tear secretion
Clinical feature:
punched out epithelial erosion
oval in shape with smooth border
Stromal disease
Necrotizing stromal keratitis:
direct viral invasion of stroma
C/F: epithelial defect
stromal necrosis
anterior uveitis ,KP
scarring, vascularization, lipid deposition
Stromal disease..
Immune stromal ( interstitial) keratitis
Retained viral antigen within stroma triggers inflammation
 Intact overlying epithelium
C/F: stromal inflammation,infiltration,neovascularization
ghost scarring/ foot prints
wessely ring
Endothelitis
Disciform keratitis (endothelitis):
Delayed hypersensitivity reaction
Microcystic epithelial edema,KP
Disc shaped area of stromal edema, central/paracentral
Descemet membrane fold
Endothelitis..
Disciform endothelitis
Endothelitis..
Diffuse endothelitis
Endothelitis..
Linear endothelitis
Recurrent ocular herpes..
Iridocyclitis:
Can occur without prior h/o keratitis
Fine KP, AC reaction
Trabeculites-raised IOP
Varicella zoster virus
Epidemiology:
Spread by saliva droplets, direct contact with cutaneous lesion
Systemic feature:
Generalized vesicular lesion, fever, malaise, rash. pneumonia ( common complication)
Ocular feature:
vesicular eruption on periocular skin & eyelid, papillary conjunctivitis
Herpes zoster ophthalmicus
HZO..
First described by Hutchinson in 1865
 Clinical entity caused by reactivation of the latent VZV from trigeminal ganglia with ocular
involvement.
Ophthalmic division of trigeminal nerve mostly affected
Hutchinson sign- vesicles at the side & tip of the nose
HZO..
Pathogenesis:
VZV transported from epithelial vesicles to sensory ganglia
Latency period: continuous active transcription
Direct co relation between increasing age & HZO
Reactivation due to inflammation/necrotic change of dorsal root ganglia
HZO pathogenesis..
Virus travels along the sensory axons to the skin
Mononuclear infiltration & multinuclear giant cell reaction
Virus enters the eyes via ciliary nerves
Perineuritis & perivasculitis around long & short ciliary nerves &vessels
HZO..
General feature:
Prodromal phase: symptom involving affected dermatome
Skin lesion:
painful erythematous area with maculopapular rash
vesicles
pustule , crust
haemorrhagic lesion
Zoster sine herpete
HZO..
Ocular feature:
Periocular skin & eyelid: maculopapular rash, vesicular skin eruption,
Conjunctiva: papillary /follicular reaction, hyperemia, and/or pseudomembrane
Sclera: episcleritis, scleritis
HZO..
Corneal changes:
Punctate epithelial keratitis- 2 days
Pseudodendritic keratitis : 4-6 days
Anterior stromal keratitis: 10 days
endothelitis: 7 days
Sclerokeratitis: 1 month
Corneal mucous plaques: 2-3 month
Disciform keratitis: 3-4 month
Neurotropic keratopathy: 2 month
Interstitial keratitis: 1-2 years
HZO-corneal changes..
PEK – 2day pseudodendrite- 4-6 day
HZO..
Nummular keratitis:
Granular sub epithelial deposit surrounded by a halo of stromal haze
Develops 10 days after onset of rash at the site of epithelial lesion
HZO-corneal changes..
Endothelitis-7-15 days serpiginious ulceration – I month
HZO..
Iridocyclitis:
Anterior uveitis
Sectoral iris ishchemia ,atrophy
Posterior uveitis: progressive retinal necrosis
Post herpetic neuralgia
Pain persist for more than one month after the rash has healed
Occur in elderly patient
Constant /intermittent pain, worse at night & aggravated by minor stimuli
M/A: ectopic activity in damaged nociceptive fibers
Adenovirus keratoconjunctivitis
adenovirus: double stranded DNA virus
Transmitted by close contact with ocular or respiratory secretions, fomite, or contaminated
swimming pool
Transmission more in populations living in close quarters, contaminated instruments, or eye
drops in physicians office
 systemic feature : upper respiratory tract infection, diarrhoea, hemorrhagic cystitis,
meningoencephalitis.
Adenovirus keratoconjunctivitis
Ocular feature:
Epidemic keratoconjunctivitis
Pharyngoconjunctival fever
Non specific follicular conjunctivitis
Epidemic keratoconjunctivitis
Serotype AD 8,9,37
C/F:
Bilateral, preceded by upper RTI
Acute watering
Foreign body sensation, photophobia, reduced vision
Lid, conjunctival edema
Follicular, papillary conjunctivitis
Hemorrhage/ membrane formation
Tender preauricular lymph node
Epidemic Keratoconjunctivitis
Stage 0: poorly staining minute punctate opacity
Stage 1: fine superficial epithelial keratitis
Stage 2: punctate, slightly raised whitish epithelial lesion.
Stage 3: coarse granular infiltrate within deep epithelium
Stage 4: sub epithelial infiltrate
Stage 5: punctate epithelial granularity
Pharyngoconjunctival fever
Serotype AD 3,7
C/F:
Fever, headache
Pharyngitis
Follicular conjunctivitis
Preauricular lymphadenopathy
Mild epithelial keratitis
Non specific follicular conjunctivitis
Serotype Ad 1,2,4,5 & 6
Mild conjunctivitis
No keratitis
Self limiting
Less common viral corneal infection
poxviridae
Variola virus
Vaccinia virus
Molluscum contagiosum virus
Cytomegalo virus
Rubella virus
Influenza virus
Viral keratitis pathogenesis

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Viral keratitis pathogenesis

  • 1. Aetiopathogenesis of viral keratitis CHAIRMAN: PROF. DR. MD. SAIFULLAH DEPT OF CORNEA, NIO&H MODERATOR: ASST PROF. DR.FARHAT JAHAN DEPT OF CORNEA , NIO&H PRESENTER: DR. SADIA YEASMIN SAKI FCPS P-2 STUDENT, NIO&H
  • 2. Viral keratitis Herpes simplex Varicella zoster Adenovirus Others(pox viridae, herpes viridae, papo viridae, picorna viridae, togaviridae)
  • 3. Herpes simplex keratitis are ubiquitous human pathogen capable of causing both asymptomatic infection & active disease Two types: HSV 1: oropharynx HSV 2: genital organ Ocular disease typically caused by type 1 Mode of infection: Humans are the only natural reservoir HSV 1: close contact, HSV 2: birth canal
  • 4. HERPES SIMPLEX KERATITIS.. VIRAL STRUCTURE: Double stranded DNA virus
  • 5. Pathogenesis-latency After peripheral entry into host & primary infection HSV travel in a retrograde fashion to various ganglia( trigeminal, cervical, sympathetic) Resides during the lifespan of the host Once ganglionic presence has been established, active replication in neuron Latency is established & presence of viral genome within the neuronal cell
  • 6. Pathogenesis-Reactivation LATS: latency –associated transcripts, a region of viral genome that is retained within host cell During latency Produced in large amount during reactivation from latency
  • 7. Reactivation source After primary infection Subclinical reactivation: periodical HSV shedding Clinical reactivation: fever hormonal change ultraviolet radiation trauma trigeminal injury
  • 9. Clinical manifestation Congenital & neonatal Primary infection Recurrent infection
  • 10. Congenital & neonatal ocular herpes Most congenital cases are acquired: genital herpes in mother during parturition HSV-2 for 80% cases Micropthalmia, retinal dysplasia, optic atrophy & chorioretinitis ( from intrauterine infection) Ocular manifestation: periocular skin lesion conjunctivitis epithelial keratitis stromal keratitis cataract
  • 11. Primary infection After 6 months-maternal anti-HSV Ig G Acute follicular conjunctivitis Keratoconjunctivitis Periocular lymphadenopathy Periocular & eyelid skin vesicles Diffuse punctate keartopathy Corneal vesicles Primary infection only confined to epithelium due to lack of previous immunologic stimulus
  • 12. Recurrent ocular herpes Clinical manifestations: blepharitis: vesicular lesion involving a focal area conjunctivitis: recurrent follicular conjunctivitis HSV keratitis Iridocyclitis
  • 14. Infectious epithelial keratitis Symptoms: discomfort, redness, photophobia, watering, blurring of vision Stellate lesion: swollen epithelial cell/ vesicle. earliest epithelial lesion Dendritic ulcer: most common presentation branching linear lesion, terminal bulbs ,swollen epithelial border  Geographic ulcer: an enlarged dendritic ulcer that is no longer linear Marginal ulcer: results from active viral disease, proximal to limbus with accompanying blood vessel
  • 15. Recurrent ocular herpes.. A) stellate lesion b)bed of dendritic ulcer with fluroscein stain
  • 16. Recurrent ocular herpes.. C) margin of dendritic ulcer, rose Bengal stain d) geographic ulcer
  • 17. Neurotrophic keratopathy Impaired corneal innervation Decreased tear secretion Clinical feature: punched out epithelial erosion oval in shape with smooth border
  • 18. Stromal disease Necrotizing stromal keratitis: direct viral invasion of stroma C/F: epithelial defect stromal necrosis anterior uveitis ,KP scarring, vascularization, lipid deposition
  • 19. Stromal disease.. Immune stromal ( interstitial) keratitis Retained viral antigen within stroma triggers inflammation  Intact overlying epithelium C/F: stromal inflammation,infiltration,neovascularization ghost scarring/ foot prints wessely ring
  • 20. Endothelitis Disciform keratitis (endothelitis): Delayed hypersensitivity reaction Microcystic epithelial edema,KP Disc shaped area of stromal edema, central/paracentral Descemet membrane fold
  • 24. Recurrent ocular herpes.. Iridocyclitis: Can occur without prior h/o keratitis Fine KP, AC reaction Trabeculites-raised IOP
  • 25. Varicella zoster virus Epidemiology: Spread by saliva droplets, direct contact with cutaneous lesion Systemic feature: Generalized vesicular lesion, fever, malaise, rash. pneumonia ( common complication) Ocular feature: vesicular eruption on periocular skin & eyelid, papillary conjunctivitis
  • 27. HZO.. First described by Hutchinson in 1865  Clinical entity caused by reactivation of the latent VZV from trigeminal ganglia with ocular involvement. Ophthalmic division of trigeminal nerve mostly affected Hutchinson sign- vesicles at the side & tip of the nose
  • 28. HZO.. Pathogenesis: VZV transported from epithelial vesicles to sensory ganglia Latency period: continuous active transcription Direct co relation between increasing age & HZO Reactivation due to inflammation/necrotic change of dorsal root ganglia
  • 29. HZO pathogenesis.. Virus travels along the sensory axons to the skin Mononuclear infiltration & multinuclear giant cell reaction Virus enters the eyes via ciliary nerves Perineuritis & perivasculitis around long & short ciliary nerves &vessels
  • 30. HZO.. General feature: Prodromal phase: symptom involving affected dermatome Skin lesion: painful erythematous area with maculopapular rash vesicles pustule , crust haemorrhagic lesion Zoster sine herpete
  • 31. HZO.. Ocular feature: Periocular skin & eyelid: maculopapular rash, vesicular skin eruption, Conjunctiva: papillary /follicular reaction, hyperemia, and/or pseudomembrane Sclera: episcleritis, scleritis
  • 32. HZO.. Corneal changes: Punctate epithelial keratitis- 2 days Pseudodendritic keratitis : 4-6 days Anterior stromal keratitis: 10 days endothelitis: 7 days Sclerokeratitis: 1 month Corneal mucous plaques: 2-3 month Disciform keratitis: 3-4 month Neurotropic keratopathy: 2 month Interstitial keratitis: 1-2 years
  • 33. HZO-corneal changes.. PEK – 2day pseudodendrite- 4-6 day
  • 34. HZO.. Nummular keratitis: Granular sub epithelial deposit surrounded by a halo of stromal haze Develops 10 days after onset of rash at the site of epithelial lesion
  • 35. HZO-corneal changes.. Endothelitis-7-15 days serpiginious ulceration – I month
  • 36. HZO.. Iridocyclitis: Anterior uveitis Sectoral iris ishchemia ,atrophy Posterior uveitis: progressive retinal necrosis
  • 37. Post herpetic neuralgia Pain persist for more than one month after the rash has healed Occur in elderly patient Constant /intermittent pain, worse at night & aggravated by minor stimuli M/A: ectopic activity in damaged nociceptive fibers
  • 38. Adenovirus keratoconjunctivitis adenovirus: double stranded DNA virus Transmitted by close contact with ocular or respiratory secretions, fomite, or contaminated swimming pool Transmission more in populations living in close quarters, contaminated instruments, or eye drops in physicians office  systemic feature : upper respiratory tract infection, diarrhoea, hemorrhagic cystitis, meningoencephalitis.
  • 39. Adenovirus keratoconjunctivitis Ocular feature: Epidemic keratoconjunctivitis Pharyngoconjunctival fever Non specific follicular conjunctivitis
  • 40. Epidemic keratoconjunctivitis Serotype AD 8,9,37 C/F: Bilateral, preceded by upper RTI Acute watering Foreign body sensation, photophobia, reduced vision Lid, conjunctival edema Follicular, papillary conjunctivitis Hemorrhage/ membrane formation Tender preauricular lymph node
  • 41. Epidemic Keratoconjunctivitis Stage 0: poorly staining minute punctate opacity Stage 1: fine superficial epithelial keratitis Stage 2: punctate, slightly raised whitish epithelial lesion. Stage 3: coarse granular infiltrate within deep epithelium Stage 4: sub epithelial infiltrate Stage 5: punctate epithelial granularity
  • 42. Pharyngoconjunctival fever Serotype AD 3,7 C/F: Fever, headache Pharyngitis Follicular conjunctivitis Preauricular lymphadenopathy Mild epithelial keratitis
  • 43. Non specific follicular conjunctivitis Serotype Ad 1,2,4,5 & 6 Mild conjunctivitis No keratitis Self limiting
  • 44. Less common viral corneal infection poxviridae Variola virus Vaccinia virus Molluscum contagiosum virus Cytomegalo virus Rubella virus Influenza virus