476 Viral Dna and Herpes Simplex Virus Ocular

Ocular disease caused by herpes simplex virus (HSV) 1 ranges in severity from a self-limiting blepharitis, conjunctivitis, or dendritic keratitis to a disciform stromal edema and necrotizing stromal keratitis that can cause blindness. Herpes keratitis and stromal disease are distinct, readily differentiable clinical entities that can be studied in animal models. In pure dendritic herpes keratitis, the virus grows in the epithelial layer of the cornea and causes dendritic ulcers of a clearly defined and characteristic shape. These ulcers may enlarge and coalesce to form "geographic" lesions of an ameboid shape. The disease subsides without scarring. Clinically, patients who have HSV infections demonstrate many varieties of corneal clinical findings. In this disease process, the tissue destruction is largely a result of virus growth. In the stromal disease model, the rabbit cornea infected with an appropriate strain first develops epithelial lesions that usually attain maximum severity 5-7 d postinfection. Shortly thereafter, disciform edema occurs and persists for several weeks. Subsequently, the stromal layer becomes opaque, with infiltration by lymphocytes, macrophages, and polymorphonuclear leukocytes. Ultimately, vascularization of the cornea and tissue necrosis ensues. In this disease process, tissue destruction appears to be a result of the immune response of the host to the antigen present in the stroma because the infectious virus has generally disappeared from the cornea by this time. The factors that determine the outcome of HSV infection of the eye are not well understood. Whereas host factors certainly play a significant part (1-4), a considerable body of evidence indicates that at least part of the disease pattern may be a reflection of the genetic properties of the infecting strain. Specifically, (a) Wander et al. (5) have shown that the type of ocular disease produced in the rabbit eye is an inherent property of the infecting strain and is independent of the titer of the infecting virus. Strains that produce epithelial disease fail to produce stromal disease regardless of