seminar on viral keratits

1. VIRAL KERATITIS
PRESENTED BY-PRAGATI JAIN

2. INTRODUCTION
• It is a common infective diseases in both developing and developed
countries.
• Herpetic eye diseases is most common infectious cause of corneal blindness
in developed countries.
• 60% of corneal ulcers in developing countries may be result of HSV.

3. Viruses Causing Keratitis
DNA VIRUSES RNA VIRUSES
HSV Type-1, Type-2 PICORNA VIRUS
VARICELLA ZOSTER VIRUS ECOVIRUS 70
ADENO VIRUS PARAMYXO VIRUS
CYTOMEGALO VIRUS MEASLES VIRUS
EPSTEIN BARR VIRUS MUMPS VIRUS
VARIOLA ORTHOMYXO VIRUS
VACCINIA INFLUENZA- A,B,C.
MOLLUSCUM CONTAGIOSUM TOGA VIRUS
PAPOVA VIRUS RUBELLA VIRUS

4. HERPES SIMPLEX VIRUS

5. • Is a member of family Herpes Viridae.
• Are ubiquitous human pathogen, causing both asymptomatic infections and active
diseases in a wide variety of end organs.
• Humans are only natural host.
• An icosahedral shaped capsid surrounds the core which contains linear double
stranded DNA .
• Basically it is epitheliotropic and may become neurotropic
• Two types-HSV-1 & HSV-2.

6. MODE OF INFECTION
• Periodic attacks tend to break out on the-
Lips,nose and cornea: HSV-1(above abdomen)
(close contact with patient suffering from herpes labialis)
Genitals: HSV-2(below abdomen)
(to eye of neonate through infected genitalia of mother & venereally))
-Poor hygiene and overcrowding-

7. PATHOGENESIS
Primary HSV-1 infection occurs most commonly in the mucocutaneous distribution of the
trigeminal nerve.
 after primary infection virus is carried to sensory ganglion for that dermatome,where latent
infection is established
 Latent virus is incorporated in host DNA, where it persists indefinitely in a latent state.

8. CLINICAL MANIFESTATION
Congenital
and Neonatal
ocular herpes
Primary
ocular herpes
Recurrent
ocular herpes

9. Congenital & Neonatal Ocular Herpes
• Can be: Intrauterine(4%)
Peripartum(10%
Post partum(86%)
• Infection to mother is-primary genital infection in early or mid gestation
• Other routes-oral lesions,maternal breast lesion,nosocomial transmission
• Localized infection will progress to disseminated diseases if untreated

10. • Ocular manifestation- Periocular skin lesion
Conjunctivitis
Epithelial & stromal keratitis
Cataract
Necrotizing chorioretinitis

11. Primary Ocular Herpes
• Usually occurs in childhood and is spread by droplet transmission.
• Due to protection by maternal antibody it is uncommon during first 6
months of life.
• Mostly infection is subclinical,or cause mild fever,malaise & URTI.
• Ocular manifestation include-Acute follicular conjunctivitis
Keratoconjunctivitis(lymphadenopathy)
Periocular & eyelid skin lesions

12. • Early involvement of cornea-Diffuse punctate keratopathy.
• Primary diseases is confined to epithelium because of lack of previous immunologic
stimulus.
• These lesions are mild and self limiting.

13. RECURRENT OCULAR INFECTION
Blepharitis Conjunctivitis
Keratitis Iridocyclitis
Fever(malaria,flu)
Hormonal changes
UV
Radiation
Trauma
Cold
Immunosuppression
(virus replicated and is transported
in sensory axons to the periphery)

14. BLEPHARITIS
• Can result from primary infection or recurrent.
• C/F-vesicular lesions involving focal area of eyelid with surrounding erythema.
• Typical lesion progresses to ulceration crusting heals without scar, unless
secondarily infected.
CONJUNCTIVITIS
• Follicular conjunctivitis,is self limiting
• May progress to keratitis

15. KERATITIS
Classification-
1.Infectious epithelial keratitis-corneal vesicles
dendritic ulcer
geographic ulcer
marginal ulcer
2.Neurotrophic keratopathy
3.Stromal keratitis- necrotizing
immune
4.Endothelitis- disciform
diffuse
linear

16. Infectious Epithelial Keratitis
• All types of recurrent infectious epithelial keratitis are caused by reactivation of live
virus.
• C/F-pain,photopbobia,thin watery discharge,decrease vision if lesion is central.
• Earliest epithelial lesion is characterized by corneal epithelial vesicles.

17. Dendritic ulcer
• Most common presentation of HSV keratitis
• Derivative of DENDRON the Greek word for Tree
• Features-branching linear lesion with terminal buds and swollen opaque epithelial cells arranged in coarse punctate or stellate
pattern that contain live virus.
Dendrites-fluorescein along the length of lesion
Swollen epithelial borders-rose Bengal(devitalized cells)
• Other associated features- Reduced corneal sensation
Mild subepithelial haze
Follicular conjunctivitis
Vesicular eye lesions

18. • Following healing there may be persistent punctate epithelial erosion and
irregular epithelium which settle spontaneously.
• Whorled epithelial appearance commonly results from prolonged topical
antiviral

19. Geographic Ulcer
• An enlarged dendritic ulcer is no longer linear and is referred as geographic
ulcer(amoeboid)
• Feature-swollen epithelial borders that contain live virus and scalloped
borders.

20. • Investigation
Scraping for culture in viral transport medium
PCR
Immunohistochemistry
Geimsa staining-shows multinucleated giant cells

21. D/D
• Herpes zoster keratitis
• Healing corneal abrasion
• Acanthamoeba keratitis
• Epithelial rejection in corneal graft
• Tyrosenemia type-2
• Toxic keratopathy secondary to topical medication

22. Treatment-
Predominantly with nucleosidide analogue that disrupt viral DNA
• TOPICAL-Aciclovir 3%
Ganciclovir 0.15%
Trifluridine
(Idoxuridine & Vidarabine are older drugs)
• DEBRIDEMENT-for resistant cases
(protects adjacent healthy epithelium and eliminates antigenic stimulus to stromal
inflammation)

23. • ORAL ANTIVIRAL THERAPY-Aciclovir 200-400mg
 Immunodeficient patients
 In children
 Pts with marked ocular surface diseases.
 Resistent cases
• CYCLOPLEGICS-Homatropine 1%
• IOP control-prostaglandin derivatives avoided
• Topical ANTIBIOTICS
• Skin lesion-Aciclovir cream
• INTERFERON MONOTHERAPY

24. • Signs of treatment toxicity-Superficial punctate erosions
Waves of whorled epithelium
Follicular conjunctivitis
Punctal occlusion(rarely)
• Persistent epithelial lesion may raise suspicion of poor or non compliance

25. Marginal Ulcer
• Results from active viral diseases.
• It has proximity to limbus with accompanying blood vessels.
• Features-epithelial lesion,infiltrated with WBC from nearby limbal vessels with adjacent limbal
injection,anterior stromal infiltrate underlying the ulcer
• More symptomatic due to intense inflammation.
• Rare and most often confused with staphylococcal marginal diseases

26. FEATURES HSV MARGINAL ULCER STAPH MARGINAL
INFILTRATE
1.ETIOLOGY Active HSV Immunologic response to staph
antigen
2.EPITHELIAL DEFECT always Absent(if present,late)
3.NEOVASCULARIZATION often never
4.PROGRESSION centrally circumferentially
5.BLEPHARITIS unrelated usually
6.LOCATION Any meridian Typically 2,4,8,10 o’”clock
meridians

27. Sequelae of Infectious Epithelial Keratitis
• Complete resolution without residual evidence.
• Stromal scarring-
sight threatning
faint,grey white subepithelial opacities c/a ghost figures or footprints of HSV
dense stromal scarring and thinning
• Dendritic epitheliopathy-abnormal appearing epithelium for several weeks after
ulcer heals.
• Stromal diseases-infectious or immune

28. Neurotrophic Keratopathy
• Neither immune nor infectious , arises from impaired corneal innervation combination with decrease
tear secretion.
• Failure of re-epithelization resulting from corneal anaesthesia.
• Features-irregularity of corneal surface.
lack of normal corneal lustre
PEE progresses to epithelial defect
 Defect is oval in shape with smooth borders , stroma beneath it is grey and opaque , may become thin
 Ulcer has thickened border formed by heaped up epithelium.

29. • Complication-stromal scarring , NVZ , necrosis , perforation , secondary bacterial infection.
• Treatment-
Stop all unnecessary topical medications .
- Artificial tears .
- Topical Antibiotics.
- Gentle debridement.
- Bandage contact lens.
- Conjunctival flapping.
- Tarsorrhaphy ( Botulinum, Surgical)

30. Stromal Diseases
• Accounts for 2% of primary infection & 20 – 48 % of recurrent infection.
• It is of 2 types
- Necrotising stromal keratitis
- Immune stromal keratitis

31. Necrotizing Stromal Keratitis
• Occurs due to active viral replication within stroma,immune mediated
• Characterised by :
- Epithelial defect. +/-
- Stromal necrosis & melting.
- Dense stromal infiltrate.
- Associated Ant.Uveitis with KP’s underlying areas of active stromal infiltration.
• Complications:
- Corneal thinning & perforation.
- Scarring
-Vascularization
- Lipid deposition.

32. Treatment-
- Topical Antiviral
- Topical antibiotics & cycloplegics.
- Conjunctival flapping & cyanoacrylate glue in cases of perforation.
- Topical Steroids can be started once epithelium heals completely.

33. Immune Stromal Keratitis
• Found in about 20% of pts with ocular HSV.
• Viral antigen in stroma triggers intrastromal inflammation.
• Overlying epithelium is usually intact.
• Characterised by:
- Stromal infiltration ( punctate)
- Stromal edema.
- Wessley immune ring
- Stromal neovascularisation
- Lipid keratopathy.
• Complications:
- Disciform keratitis
- Scarring

34. • Treatment-
-Topical steroids
- Topical Antivirals
- Topical Antibiotics, Lubricants & Cycloplegics.
- Oral steroids in severe cases.

35. Endothelitis
• Pathogenesis unknown,may be immunologic.
• Classified on the distribution of KP & configuration of overlying stroma
and epithelial oedema- 1.Disciform
2.Diffuse
3.Linear

36. Disciform Endothelitis
• C/F- blurred vision with haloes around light
discomfort
redness
• Signs- central zone of stromal oedema,often with overlying epithelial oedema
granulomatous KP underlying oedema
DM folds in severe cases
WESSELY RING signifies deposition of viral Ag host Ab complex.
IOP may be increased
Decreased corneal sensation

37. • Treatment-
-Topical steroids with antiviral cover-prednisolone1% or dexamethasone0.1%
-Monitor IOP
-Cycloplegics for comfort if needed
-With active epithelial lesion-steroid as low as possible,more frequent antiviral regimen
-Oral steroids- . severe stromal inflammation
.reduce steroid induced IOP elevation
.avoid viral promotion in infectious viral keratitis
-Topical ciclosporin 0.05%
-Fine needle diathermy and laser technique.

38. Diffuse Endothelitis
• Scattered KP spread over the entire endothelium
• Stromal oedema involving entire cornea
• Microcystic epithelial oedema
• T/t-topical and systemic steroids
antivirals

39. Linear Endothelitis
• Line of KP from limbus,may be sectoral or circumferential
• Edema present peripheral to line of KP,extending to limbus
• Microcystic epithelial oedema
• T/t-topical and systemic antivirals and corticosteroids
• Corneal decompensation is common

40. IRIDOCYCLITIS
 Can occur without s/o active corneal inflammation
 Patchy iris atrophy,IOP elevation due to trabeculitis
 Aqueous sampling for PCR is diagnostic
 T/t-topical steroids and adjunctive oral Acyclovir

41. Keratoplasty
• Recurrence of herpetic eye diseases and rejection is common and threaten
survival of corneal graft
• Topical antivirals-during rejection episode to reduce epithelial viral
reactivation
• Prophylactic oral Acyclovir- 400mg BD improves graft survival rate
To be given to pts undergoing penetrating keratoplasty

42. HEDS
(multicentre,randomized,placebo-controlled trials)
• PURPOSE- RESULT-
 Topical corticosteroid in t/t of stromal
keratitis already on antiviral E/D
 Oral acyclovir in t/t stromal keratitis already
on steroid and antiviral E/D
 Oral acyclovir in t/t iridocyclitis already on
steroid e/d
 Oral acyclovir in preventing recurrence of
epithelial and stromal keratitis
 Oral antiviral prophylaxis reduces
recurrences of epithelial & stromal
keratitis
 Use of topical corticosteroid is of benefit
in stromal keratitis
 Use of oral acyclovir may help in
iridocyclitis
 Prophylactic oral acyclovir helps prevent
recurrences of herpetic
keratitis,particularly with H/O recurrence

43. No Corticosteroids
.HSV conjunctivitis
.Infectious epithelial
keratitis
.Non-inflamed
neurotrophic
keratopathy
Topical Steroids:
.Marginal keratitis
.Moderate IK
.Moderate Disciform &
diffuse Endothelitis.
.Inflamed Neurotrophic
keratopathy.
Oral steroids:
.Severe IK
.Severe Disciform &
Diffuse Endothelitis.
.All cases of Linear
Endothelitis.

44. HERPES ZOSTER

45. • Varicella zoster virus also referred as human herpes virus type 3.
• Ubiquitous
• Causes-varicella(chickenpox) & herpes zoster(shingles)
Represents
primary
infection
Results from
reactivation of the
latent VZV within
sensory spinal or
cerebral ganglia

46. • Herpes zoster derives its name from Greek word HERPEIN-to spread,to creep
Zoster-girdle or zone.
• Life time risk of herpes zoster is 10-30%

47. RISK FACTORS
• Increasing risk(>70 years)
• Neoplastic diseases
• Immunosuppressive drugs
• Organ transplant recepients
• HIV
• Others-syphilis,TB,malaria,emotional &physical stress

48. HUTCHINSON’S
SIGN
Vesicles at the side or tip of
the nose are potential
indicators of ocular diseases

49. Pathogenesis
• Humans are only known natural host to VZV
• Structure-core of double stranded DNA surrounded by icosahedral
nucleocapsid with an outer cell membrane containing
glycoproteins,carbohydrates,lipids.
• This outer envelope helps in attachment and penetration of virus into
human

50. After primary infection with VZV
Virus transported from varicella vesicular lesion along sensory axons or via
haematogenous route to dorsal roots or TG and neural cell bodies
Enters state of latency
Disturbance in symbiosis of virus and host initiates reactivation
Virus replicates and travel to skin and mucous membrane via axonal transport
(reactivation thought to occur after VZV specific cell mediated immunity has faded)

51. Acute shingles
• A prodromal phase-
Precedes the appearance of the rash, It lasts 3–5 days
Characterized by tiredness, fever, malaise and headache.
Symptoms-superficial itching, tingling or burning sensation to a severe boring
or lancing pain that is either constant or intermittent.

52. • Skin lesions
 Painful erythematous areas with a maculopapular rash which respects the midline.
 Within 24 hours, groups of vesicles appear and these become confluent over 2–4
days.
 Boggy oedema of the upper and lower lids is common and often spreads to the
contralateral side of the face.
 Vesicles pass through a pustular phase crust and dry after 2–3 weeks.
 Large, deep haemorrhagic lesions in immunodeficient patients
 Lesions heal to leave residual skin destruction and depigmented scars
 Zoster sine herpete is shingles without a rash.

53. • Disseminated zoster involving multiple dermatomes and organ systems
may develop in immunodeficiency or malignancy
• Investigation.
Vesicular fluid -PCR, immunomicroscopy or culture(rarely).
PCR of plasma for VZV DNA -positive (40%), especially in
immunosuppressed patients and zoster sine herpete.
 IgM antibodies to VZV-minority of early stage and convalescent patients

54. Treatment-
• Oral antiviral- within 72 hours of rash onset, still at the vesicular stage also derive benefit from
treatment.
Aciclovir (800 mg 5 times/day-7–10 days) has been the mainstay of treatment,
Newer agents- valaciclovir 1 g TID or famciclovir 250–500 mg TID have more convenient
regimens, are better tolerated and are at least as effective as Aciclovir..
• Intravenous Aciclovir 5–10 mg/kg TID in encephalitis, and immunocompromised individuals
• Systemic steroids -Prednisolone in tapering doses.

55. • Symptomatic t/t of skin lesions- drying, antisepsis and cold compresses.
• Patients with shingles can transmit chickenpox so that contact with people not known to be
immune (particularly pregnant women) and immunodeficient individuals should be avoided
at least until crusting is complete.

56. ACUTE EYE DISEASES
• Acute epithelial keratitis-
Develops in over 50% of patients within 2 days of the onset of the rash
usually resolves spontaneously. (4-6 days)
Features-dendritic lesions that are smaller and finer , and have tapered ends
without terminal bulbs, stain better with rose Bengal than with fluorescein.
(PSEUDODENDRITES)
 Treatment- if required, is with a topical antiviral.

57. • Nummular keratitis-
 Develops at the site of epithelial lesions about 10 days after the onset of the rash.
 Characterized by fine granular subepithelial deposits surrounded by a halo of stromal haze
 The lesions fade in response to topical steroids but recur if treatment is discontinued
prematurely.
• Episcleritis-
 occurs at the onset of the rash and usually resolves spontaneously.
 A mild NSAID may be used if necessary.

58. • Scleritis and sclerokeratitis-are uncommon.
 May develop at the end of the 1 week.
Treatment of indolent lesions is with oral flurbiprofen 100 mgTID
Oral steroids with antiviral cover.

59. • Stromal (interstitial) keratitis-
Develops 3 weeks after the onset of the rash
 It usually responds to topical steroids but can become chronic and require slow tapering.
• Disciform keratitis (immune-mediated endotheliitis)- 3-4 months
 Is less common than with herpes simplex infection but may lead to corneal decompensation.
Treatment is with topical steroids.
• Anterior uveitis-
Affects at least a third of patients and can be associated with sectoral iris ischaemia and atrophy.

60. • Posterior uveitis-.
Progressive retinal necrosis is an aggressive retinitis usually occurring in
immunodeficient individuals.
ARN
 Posterior segment examination should always be performed in patients with HZO
• IOP should be monitored- as elevation is common, including steroid-induced.
Prostaglandin derivatives should be avoided if treatment is necessary. •

61. • Neurological complications-
Cranial nerve palsies- 3rd (most common), 4th and 6th nerves usually
recover within 6 months.
 Optic neuritis is rare.
 CNS manifestations are rare but include encephalitis, cranial arteritis, and
Guillain–Barré syndrome

62. CHRONIC EYE DISEASES
• Neurotrophic keratopathy- similar to that seen in HSV infection develops in up to about 50% (2 months)
• Scleritis may become chronic and lead to patchy scleral atrophy
• Mucous plaque keratitis
 develops in 5%, most commonly b/w third and sixth months, characterized by elevated mucous plaques
staining with rose Bengal (2-3 months) .
 Treatment-combination of topical steroid and acetylcysteine.
 Untreated, plaques resolve after a few months, leaving a faint diffuse corneal haze.

63. • Lipid degeneration-may develop in eyes with persistent severe nummular
or disciform keratitis . (1-2 years)
• Lipid-filled granulomata -may develop in the tarsal conjunctiva, and may
progress to erosive calcified concretions.
• Subconjunctival scarring may occur.
• Eyelid scarring- ptosis, cicatricial entropion and occasionally ectropion,
trichiasis, lid notching & madarosis.

64. POST HERPETIC NEURALGIA
o Defined as pain that persists for more than one month after the rash has
healed.
o It develops in up to 75% of patients over 70 years of age.
o Pain may be constant or intermittent, worse at night and aggravated by
minor stimuli (allodynia), touch and heat.
o Neuralgia can impair the quality of life, and may lead to depression of
sufficient severity to present a danger of suicide.

65. Treatment
• Local - Cold compresses.
- Topical capsaicin 0.075% or lidocaine 5% patches.
• Systemic- Simple analgesics such as paracetamol.
- Stronger analgesics such as codeine.
-Tricyclic antidepressants, nortriptyline, amitriptyline, initially 25 mg nightly adjusted
up to 75 mg for several weeks if necessary.
- Carbamazepine 400 mg daily for lancinating pain.
- Gabapentin (300–600 mg TID),
-Sustained-release oxycodone (10–30 md BD), or both.

66. ADENOVIRUS

67. ADENOVIRAL KERATITIS
• Causative agent for epidemic keratoconjunctivits
• Caused by serotype 8,19,37
• Highly contagious,via hands and fomites
• Corneal trauma facilitates infection
• Incubation period-8 days

68. • Symptoms-insidious onset
Pain,photophobia,watering
Children may have fever and lymphadenopathy.
• Associated with-Follicular keratoconjunctivits
Palpebral oedema
Preauricular lymphadenopathy(pathognomic)
Haemorrhagic conjunctivits

69. • STAGE-1:corneal epithelial vesicle like elevation,25-30 microns.
• STAGE-2:2-5 days later,lesions coalesce and involve deeper epithelium,classical
epithelial punctate kaeratitis lesion.
• STAGE-3:faint subepithelial infiltrates present beside the punctate keratitis.
• STAGE-4:nummular opacities,may be present weeks to month after initial episode.
(residual scarring & visual impairment may occur)

70. • Treatment-
Artificial tears
Topical vasoconstrictors
Steroids
Cold compress

71. THANK YOU