viral reactivation and subsequent clinical recurrent disease.

Clinical Features

Primary ocular HSV usually occurs as an acute follicular conjunctivitis with preauricular adenopathy, with or without vesicular ulcerative blepharitis or periocular cutaneous involvement, and punctate or branching epithelial keratitis. The virus establishes a latent infection, which may recur under different types of neuronal stimuli.

Recurrent ocular HSV is mainly characterized by keratitis, including epithelial keratitis (dendritic ulcers, geographic ulcers, and metaherpetic ulcers), stromal keratitis (necrotizing, interstitial, or disciform keratitis, immune rings, and limbal vasculitis), and endotheliitis. Dendritic or geographic ulcers are caused by direct viral invasion; necrotizing stromal keratitis is caused by direct viral invasion and by immune complex hypersensitivity immune disease [206, 212]; interstitial stromal keratitis, immune rings, limbal vasculitis, and peripheral ulcerative keratitis are caused by immune complex hypersensitivity immune disease; disciform keratitis is caused by delayed hypersensitivity immune disease; endotheliitis may be caused by active viral invasion or by immune disease; metaherpetic ulcers are caused by trophic factors.

Uveitis and retinitis also may occur in recurrent HSV. Episcleritis and scleritis are uncommon.

Scleritis

Direct HSV invasion (often with epithelial infectious ulceration or necrotizing stromal disease) or the host immune reaction to the virus (often with necrotizing or interstitial stromal keratitis, immune rings, limbal vasculitis, disciform keratitis, or peripheral ulcerative keratitis) may cause scleritis. Active infectious scleritis is usually of the diffuse or nodular type [37]; immune-medi- ated scleritis is most often of the necrotizing type. Corneal-conjunctival-scleral biopsy, using antiHSV type 1 antibodies may reveal positive detection of HSV type 1 antigens in cornea, conjunctiva, and sclera [206].

In our prior series of 172 patients with scleritis [13], two patients had scleritis associated with

HSV infection (1.16%). One patient was a 49-year-old white male with a maxilla osteosarcoma that required bone removal and multiple debridement and bone grafts because of secondary osteomyelitis (see section on ÒSystemic InfectionsÓ in Chap. 5). While receiving antibiotics via a continuous intravenous central line antibiotic pump, the patient developed blotchy white inÞltrates in the corneal stroma and diffuse scleritis adjacent to the corneal inÞltration. Immunoßuorescence studies of the corneo-con- junctiva-scleral biopsy, using anti-HSV type 1 antibodies, revealed positive detection of HSV type 1 antigens in cornea, conjunctiva, and sclera. Treatment with acyclovir and steroids resolved the process.

The second patient was a 77-year-old white male with multiple recurrences of HSV dendritic keratitis who developed necrotizing scleritis and peripheral ulcerative keratitis in his right eye 1 month after the last active infectious episode. An extensive systemic review of systems was negative. Histopathologic examination of the conjunctiva and scleral biopsies revealed granulomatous inßammation with epithelioid and multinucleated giant cells, and inßammatory microangiopathy in both tissues; immunoßuorescence studies with anti-immunoglobulins and anti-complement antibodies revealed immune complex deposition in the vessel walls in both tissues; immunoßuorescence studies with anti-HSV type 1 antibodies were negative in both tissues. SuperÞcial keratectomy and conjunctival-scleral debridement followed by cornescleral grafting stopped the progression of the process. Keratoscleritis in this patient seemed to have been caused by an autoimmune mechanism induced by HSV type 1.

Episcleritis

Episcleritis may rarely occur in HSV infection [17, 213Ð215]. It may be simple or nodular and is often accompanied by areas of lymphocytic inÞltration manifested as yellow spots in conjunctiva and episclera, or by dendrites in cornea [17]. Episcleritis is usually the result of direct viral invasion and resolves in a few weeks without sequelae. Recurrences are not unusual.