In our prior series of 94 patients with episcleritis [13], one patient had episcleritis associated with HSV infection (1.06%). The patient was a 64-year-old white female who developed a follicular conjunctivitis; there were also vesicles in bulbar conjunctiva and episclera with surrounding redness and edema in the absence of keratitis. Treatment with trißuridine resolved the inßammation completely in 1 week. Visual acuity was not affected. Unfortunately, scrapings for cytology, antigen detection, or cultures were not taken.

Diagnosis

Although often clinically characteristic, diagnosis of either primary or recurrent active ocular HSV infection can be assisted with laboratory techniques. Giemsa or Papanicolaou staining may show eosinophilic intranuclear inclusions, ballooning degeneration, multinucleated giant cells, and monocytic inÞltration (indistinguishable from VZV) from corneal dendrite or skin vesicle scrapings; conjunctival swabbing is not usually helpful, unless there is follicular conjunctivitis with or without episcleritis. HSV-1 antigen may be detected by immunoßuorescence assays performed on scrapings (corneal dendrite, upper palpebral conjunctiva, and skin vesicle) or tissue biopsies (skin, cornea, conjunctiva, episclera, and sclera) [206]. HSV causes a cytopathic effect in ordinary tissue cultures (HeLa cells, human amnion cells, or Vero cells). Herpes virus also may be detected by electron microscopy studies, but HSV and VZV are indistinguishable. Serology may differentiate primary HSV infection from recurrent HSV infection because only primary infection shows an increase in HSV type 1 antibody titer: negligible titers are found during the acute phase and considerably higher titers are found 4Ð6 weeks later. Because most adults have developed an anti-HSV antibody titer indicating prior, usually asymptomatic or subclinical, primary infection, absence of antibody can help to exclude HSV as a cause of atypical keratitis.

HSV immune-mediated keratitis and/or scleritis diagnosis is suggested by clinical Þndings in a patient with a prior history of herpetic epithelial keratitis. There is no current laboratory method

available to substantiate HSV as the responsible agent of the immune damage.

Therapy

Active HSV infection, including epithelial keratitis, scleritis, or episcleritis, may be treated with topical antiviral agents, such as idoxuridine, vidarabine, trißuridine, or acyclovir [206]. Trißuridine (1% drops, one drop nine times a day for 14Ð21 days) and acyclovir (3% ophthalmic ointment, one application Þve times a day), are the most effective agents in clinical trials [216, 217], although acyclovir ointment is available only on a compassionate plea basis in the USA. Idoxuridine and vidarabine remain effective agents and can be used in the absence of a history of drug failure or intolerance. Long-term oral acyclovir (200 mg, Þve times a day) signiÞcantly reduces recurrences of HSV epithelial keratitis (Pavan Langston D: Systemic acyclovir in herpes simplex keratitis. Personal communication, New England Ophthalmological Society Meeting, Sept 13, 1991); we may assume that long-term oral acyclovir may also decrease recurrences of episcleritis or scleritis due to active viral invasion. Long-term oral acyclovir has been shown to reduce recurrences of HSV keratitis following penetrating keratoplasty [218].

Therapeutically, the same rules apply to the treatment of immune-mediated scleritis secondary to HSV as to immune-mediated scleritis secondary to VZV (see Sect. 7.3.1.1). If systemic or topical steroids are used, concomitant prophylactic antiviral agents, such as topical trißuridine drops (four times a day) or oral acyclovir (200 mg, Þve times a day), should be used.

Our Experience

In our current series of 500 patients with scleritis, 35 patients had herpetic scleritis (7%). The most common type of scleritis was diffuse in 80% of the patients, followed by nodular (11.4%), and necrotizing in 8.6%. The scleritis was most often unilateral (80%) and associated with keratitis and/or anterior uveitis with subsequent loss of vision. Herpes virus infection was conÞrmed by anti-HSV and anti-HZV immunoßuorescent analysis of scleral specimens in 16 patients. Diagnosis was presumptive by unequivoval Þndings of dendritic or stromal