viral keratitis
TRANSCRIPT
VIRAL KERATITIS
Introduction Viruses are obligate intracellular parasites that contain
only one type of nucleic acid within he infectious unit and are unable to replicate by binary fission.
Viruses that cause corneal disease are Herpes simplex ( HSV) Varicella zoster ( VZV) Epstein Barr ( EBV) Adenovirus Cytomegalovirus (CMV) can also cause keratitis and
is more commonly associated with AIDS
Epidemiology and pathogenesis
HSV, VZV, EBV, and CMV are all members of the family Herpesviridae.
DNA viruses There are two types of HSV HSV-1 is more commonly associated with
labial and ocular infection. HSV-2 is associated with genital infection.
Ophthalmology 2004, (2), 475-481
Epidemiology and pathogenesis
Herpes simplex keratitis is a leading cause of corneal blindness in the developing world.
Estimated prevalence is approx 150 per 100,000 population.
Ocular HSV tends to be a unilateral disease with only one eye affected by primary disease in approx 80-90% of cases.
Atopy appears to be risk factor for bilateral disease, & is associated with gastric cancer, lumbar zoster, malaria and pulmonary tuberculosis
HERPES SIMPLEX KERATITIS
Herpes Simplex Keratitis occurs in two forms:
1. Primary
2. Recurrent
Primary HSV-1 (HSV type 1) infections Occurs most commonly in the mucocutaneous distribution of the trigeminal nerve.
spread of Primary virus Infected Nearby Infection epithelial cells sensory nerve
endings
Viral genome Cell body in transport along
enters nucleus trigeminal ganglion nerve axonat neuron
(Persists indefinitely in a latent state)
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PRIMARY HSV-1 Primary infection of any of the 3 branches
(ophthalmic, maxillary, mandibular) of cranial nerve V leads to latent infection of nerve cells in trigeminal ganglion.
Interneuronal spread of HSV within ganglion allows patients to develop ocular disease without ever having had primary ocular HSV infection.
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RECURRENT HSV INFECTION Has been thought of as reactivation of virus in the
sensory ganglion. Virus migrates down nerve axon to produce lytic
infection in ocular disease. Recent evidence suggests, virus may subsist
latently within corneal tissue, serving as a potential source of recurrent disease.
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CLINICAL FINDINGS
Primary Herpes Simplex Keratitis Infrequently seen Manifested as vesicular blepharoconjunctivitis
occasionally with corneal involvement Usually occurs in young children Topical antiviral therapy may be used as
prophylaxis and as therapy
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CLINICAL FINDINGS Recurrent type herpetic keratitisAttacks triggered by Fever Overexposure to UV light Trauma Onset of menstruation Local/ systemic source of immunosuppression Bilateral lesions develop in 4-6% of patients and
seen mostly in atopic patients.
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SYMPTOMS Irritation Photophobia Tearing Reduction in vision (when central cornea is
affected) Corneal anesthesia usually occurs early in
the course of infection and thus symptoms may be minimal.
SYMPTOMS Corneal ulceration can occasionally be the
only sign of recurrent herpetic infections
Recurrent herpes simplex virus dendritic ulcer with an adjacent stromal scar
LESIONS: Dendritic ulcer Most characteristic lesion, occurs in corneal
epithelium Typical branching, linear pattern with feathery
edges and terminal bulbs at ends. Visualized by fluorescein staining
HSV dendritic ulcer stained with fluorescein
Dendritic keratitis
This patient suffers from herpetic keratitis. Fluorescein staining reveals dendritic ulcer typical of herpes keratitis. This is treated with topical 3% acyclovir
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Geographic ulceration Form of chronic dendritic disease. Delicate dendritic lesions take a broader
form. Corneal sensation is diminished
HSV geographic ulcer
Other corneal lesions Other corneal epithelial lesions caused by HSV
are Blotchy epithelial keratitis Stellate epithelial keratitis Filamentary keratitis Usually transitory, often become typical dendrites
within a day or two.
Filamentary keratitis
Subepithelial lesions Caused by HSV infection Ghost like image, larger than original
epithelial defect seen in the area immediately underlying epithelial lesion.
Does not persist for more than a year
Disciform keratitis Most common form of stromal disease in HSV infection. Edematous stroma without significant infiltration and
usually without vascularization. Edema is most prominent sign. Keratic precipitates may lie directly under disciform lesion
but may also involve the endothelial lesion.
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Peripheral lesions of the cornea Caused by HSV Usually linear lesions, show loss of
epithelium Testing for corneal sensation is unreliable. Patient is far less photophobic than patients
with nonherpetic corneal infiltrates.
Treatment Should be directed at eliminating viral
replication within the cornea, while minimizing damaging effects of inflammatory response.
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Treatment DEBRIDEMENT Epithelial debridement is an effective way
to treat dendritic keratitis Infected epithelium is easy to remove with
tightly wound cotton tip applicator. Adjunctive therapy with topical antiviral
accelerates epithelial healing.Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137
Treatment
Ophthalmology 2004, (2), 475-482
Antiviral medicines used in treatment of Herpes Simplex Virus
Ocular Disease
Activated by viral thymidine kinase to inhibit DNA polymerase
5 times daily
400 mg 5 times daily
3% ointment
200/400/
800 DT
Topical
Oral
Acyclovir
Inhibits viral thymidylate synthetase
Every 2 hours while awake
1% solution
TopicalTrifluridine
Inhibits viral DNA polymerase
5 times daily3% ointment
TopicalVidarabine
Inhibits viral thymidine kinase, thymidylate kinase and DNA polymerase
Hourly while awake
0.1% solution
TopicalIdoxuridine
ActionFrequencyFormRouteAntiviral
Ophthalmology 2004, 2; 475-482
TREATMENT : DRUGS
Treatment Trifluridine and acyclovir are much more
effective in stromal disease than others. Idoxuridine and trifluridine are frequently
associated with toxic reactions. Oral acyclovir may be useful in treatment of
severe herpetic eye disease particularly in atopic individuals.
Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137
Treatment Oral acyclovir : DOSAGE: For active treatment 400 mg five times daily in
nonimmunocompromised patients. 800 mg five times daily in compromised and atopic patients. Prophylactic dosage in recurrent disease is 400 mg twice daily.
Famciclovir or valacyclovir may also be used. Topical corticosteroids accelerate corneal thinning, increasing
risk of corneal perforation.
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Surgical treatment Penetrating keratoplasty indicated for visual rehabilitation
in patients with sever corneal scarring. Should not be undertaken until herpetic disease has been inactive for many months.
Systemic antiviral agents should be used for several months after keratoplasty to cover use of topical steroids.
Lamellar keratoplasty has advantage over penetrating keratoplasty of reduced potential for corneal graft rejection.
Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137
Varicella zoster viral keratitis (VZV) Occurs in two forms: Primary ( varicella) Recurrent ( herpes zoster)
Ocular manifestations are uncommon in varicella but common in ophthalmic zoster.
Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137
Varicella zoster viral keratitis (VZV)Ocular manifestations Usual eye lesions are pocks on lids and lid
margins. Keratitis occurs rarely. Epithelial keratitis with or without
pseudodendrites occurs more rarely. Disciform keratitis with uveitis of varying
duration has been reported.
Ophthalmic herpes zoster
Is accompanied by keratouveitis that varies in severity according to immune status of the patient.
Children with zoster keratouveitis usually have benign disease, aged have severe and sometimes blinding disease.
Corneal complications in ophthalmic zoster often occur if there is skin eruption in areas supplied by branches of the nasociliary nerve.
Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137
Distinguishing features of dendrites associated with HSV versus VZV
Feature HSV VZV
Overall Fine, lacy Thick ropy
Epithelium Linear defect with bared stroma, surrounded by edematous epithelial cells
Elevated, painted-on appearance
Staining Base stains with fluorescein. Diseased border epithelial cells stain with rose bengal
Minimal fluoroescein staining
Terminal bulbs Frequent None
Treatment Intravenous and oral acyclovir have been used
successfully for treatment of herpes zoster ophthalmicus, particularly in immunocompromised patients.
Oral dosage is 800 mg five times daily for 10-14 days.
Therapy needs to be started within 72 hours after appearance of the rash.
Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137