Viral Keratitis

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

Vaughan & Asbury’s General Ophthalmology 16th Edition, 136

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.


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.


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.

Vaughan & Asbury’s General Ophthalmology 16th Edition, 136-137

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.


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.


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.


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.


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.


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.


Viral Keratitis

Documents

stromal disease

recurrent

ophthalmic

corneal sensation

disciform

terminal bulbs

nerve axon

vaughan amp