Ocular Pathology

Anatomy and pathology of the human eye. Use it to review eye pathology for Ophthalmology Board Review or OKAP.

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Wednesday, February 14, 2007

Herpes Simplex Virus Stromal Keratitis

Definition: Herpes simplex virus keratitis is a viral infection of the cornea caused by Herpes simplex. It is characterized in early stages by a linear arborizing pattern of opacification and swelling of epithelial cells called a dendrite (green arrow represent the histologic appearance of the dendrite captured in this rare image). This involvement may be self limited or may in recurrent episodes progress to a severe keratouveitis with vision threatening consequences.
Incidence/Prevalence: In the US: Approximately 20,000 new cases of ocular HSV occur in the United States annually, and more than 28,000 reactivations occur in the United States annually. Of the US population, a history of external ocular HSV infection is present in 0.15%. HSV keratitis is one of the most frequent causes of corneal blindness in the United States with 500,000 people experiencing HSV-related ocular disease.
Etiology: Herpes simplex vius has been isolated from corneas in some cases of chronic stromal keratitis by culture, electron microscopy, PCR and immunohistochemistry.
Clinical Findings: The clinical manifestations vary according to the stage of infection. The first attacks are painful, with photophobia, tearing, ciliary injection. A dendrite composed of a plaque of opaque cells may be evident. This is followed by a dendritic ulcer, then a subepithelial infiltrate. There may be slight cell and flare. Vesicles and ulcers may occur concomitantly on the mucosa or lids.
In later attacks there may be a foreign body sensation and cornea becomes more hypoethestic. The attacks may feature stromal keratouveitis with deeper ocular structures being involved. The cornea may show granular opacities or a florid necrotizing keratitis with ulceration. In the photograph, there is a discoid infiltrate (arrows 1) in a red eye with a severe inflammatory reaction (number 2). A Wessely ring (presumably immune in origin) may be present. Vascularization and scarring follow. There is usually epithelial edema, endothelial inflammation (see arrow 1 below) and uveitis. There may be posterior synechiae, rubeosis irides, secondary glaucoma.

Histopathology: The overview of most pathology cases shows marked thinning of the central stroma (notice the thinned central stroma between the red arrows). Previous ulceration leaves a stroma divot in which hyperplastic epithelium may partially fill the gap (red arrows). Sections generally show evidence of epithelial hydropic changes with disruption and an irregularly thinned, disrupted and frequently absent Bowman’s layer (arrow3) that may be replaced by inflammatory pannus. There is accompanying chronic inflammation usually in the anterior stroma (arrow 2) but often in the posterior stroma in severe cases. There may be disruptions in Descemet’s membrane and a retrocorneal fibrous and inflammatory membrane. Note the pigmented laden macrophages arrow 1. The inflammation is often granulomatous. The finding of giant cells and histiocytes on Descemet’s membrane (arrows 4 and 5, respectively) or between Descemet’s membrane and the stroma should invoke a careful search for inclusions of Herpes keratitis. Immunohistochemistry may show reactivity of antibodies directed against Herpes antigens. In this case stromal keratocytes react strongly to anti-HSV 1&2 antigens (lighted arrow).
Corneal scrapings obtained from a dendrite and prepared using the Giemsa stain will reveal the presence of intranuclear viral inclusions (Cowdry A) that have a ground glass appearance. Infected epithelial cells may coalesce to from multinucleated giant cells.

Treatment: Herpetic stromal keratitis can be treated with topical prednisolone drops every 2 hours accompanied by a prophylactic antiviral drug such as trifluridine or acyclovir. The steroid drops are tapered slowly and antiviral agent prevents reinfection with shed virus.
Prognosis: One of the hallmarks of herpes simplex virus (HSV) infection is the establishment of a lifelong latent infection accompanied by periods of recurrent disease. The course depends on the severity of recurrences and the ensuing complications including indolent and stromal ulceration, uveitis, synechiae, rubeosis irides, secondary infection and secondary glaucoma.

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