Ocular Disease Caused by DNA Viruses

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DNA viruses (Table 2) are responsible for most significant ocular viral infections in the industrialized world. Even the protean ocular manifestations of the HIV, an RNA virus, result largely from reduced immunity to DNA viruses.

Adenovirus is probably the most common DNA virus to cause eye disease. Three common ocular syndromes have been identified. Simple follicular conjunctivitis occurs with infection by many adenovirus types and may be subclinical. Pharyngoconjunc-tival fever typically follows infection with adenovirus types 3, 4, and 7. As the name implies, patients have pharyngitis, conjunctivitis and fever, and may be misdiagnosed as having influenza. Epidemic keratoconjunctivitis, most often caused by adenovirus types 8, 19 and 37, is a highly contagious syndrome with significant morbidity. The conjunctivitis can be severe (Fig. 3); associated inflammatory conjunctival membranes can permanently scar the eyelids to the globe. Corneal involvement begins as a punctate epithelial keratitis and may proceed to a large central epithelial ulcer. Stromal keratitis presents about 2 weeks after the conjunctivitis as multifocal subepithelial corneal infiltrates, and causes both foreign body sensation and reduced vision. The stromal infiltrates may resolve spontaneously, but can become chronic, require long-term treatment with corticosteroids, and cause persistent visual morbidity. A fourth ocular syndrome occasionally associated with adenovirus infection, AHC (discussed above) may be caused by adenovirus type 11. Interestingly, adenovirus type 11 also causes acute hemorrhagic cystitis. Follicular conjunctivitis clinically indistinguishable from adenovirus conjunctivitis can also be caused by Newcastle disease virus, an RNA virus that gives rise to fatal epidemics in poultry and infects the birds' human handlers.

The human herpes viruses are preeminent among DNA viruses in eye disease with at least seven of the eight known human herpes viruses associated with ocular disorders. Herpes simplex virus type 1 (HSV-1) is the most common herpes virus to cause eye disease and herpes simplex keratitis is the most common cause of infectious blindness in the industrialized world. HSV-1 causes self-limited and relatively benign infections of the eyelids, the conjunctiva and the corneal epithelium, but infections of the corneal stroma, uvea and retina may result in chronic or recurrent blinding stromal keratitis, uveitis and retinal necrosis, respectively. Elevation of intraocular pressure due to involvement of the trabecular mesh-work is not uncommon and may help to differentiate herpetic uveitis from noninfectious causes. Post-natally acquired HSV-2 ocular infection, less common than HSV-1, causes disease similar in most respects to HSV-1. Neonatal herpes simplex infection, acquired during transit through the birth canal and usually due to HSV-2, commonly causes vesicular blepharitis and conjunctivitis, but can also cause permanent visual loss due to keratitis, chorioretinitis, optic neuritis and encephalitis of the visual cortex.

Varicella zoster virus, the etiologic agent of chickenpox and shingles, rarely causes keratouveitis with primary infection (chickenpox). However, vision-threatening keratitis, uveitis, and less commonly, retinal necrosis, are complications of varicella zoster virus reactivation in the distribution of the fifth cranial nerve (zoster ophthalmicus). Lid ulceration with frank tissue loss or lid malposition leads to corneal exposure and ulceration. Optic neuritis and cranial nerve paresis can accompany onset of the zoster rash. Sectoral iris atrophy is pathognomonic for zoster ophthalmicus. Postinfectious corneal anesthesia and secondary sterile corneal ulceration may follow herpes simplex types 1 and 2, but are most severe in zoster ophthalmicus. Chronic scleritis, keratitis, uveitis and glaucoma may ultimately limit the visual acuity.

Acute systemic infection with Epstein-Barr virus may cause conjunctivitis and epithelial keratitis. Stromal keratitis occurs but is difficult to differentiate

Table 2 Ocular targets of human DNA viruses

Virus

Family

Subfamily/genus

Nucleic acid

Env. Ocular target

Adenovirus

Herpes simplex virus, type 1 (HHV1)

Herpes simplex virus, type 2 (HHV2)

Varicella zoster virus (HHV3)

Epstein-Barr virus (HHV4)

Human cytomegalovirus (HHV5) Human herpes virus 6 (HHV6) Human herpes virus 8 (HHV8) Human papillomavirus

Molluscum contagiosum virus

Orf virus

Smallpox (variola) virus

Vaccinia virus

Adenoviridae

Herpesvlridae

Herpesviridae Herpesvlridae Herpesviridae Papovaviridae

Poxviridae

Poxviridae Poxviridae

Poxviridae

Mastadenovirus

Simplexvirus

Simplexvirus

Varicellovirus

Lymphocryptovirus

Betaherpesvirinae/ Cytomegalovirus Betaherpesvirinae/ Roseolovirus

Papillomavirus

Molluscipoxvlrus

Parapoxvirus Orthopoxvirus

Orthopoxvirus

Lymphocryptovirus

Betaherpesvirinae/ Cytomegalovirus Betaherpesvirinae/ Roseolovirus

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