Pathogenesis of herpes simplex keratitis: The host cell response and ocular surface sequelae to infection and inflammation

Abstract Herpes simplex virus type 1 (HSV) keratitis is a leading cause of infectious blindness. Clinical disease occurs variably throughout the cornea from epithelium to endothelium and recurrent HSV stromal keratitis is associated with corneal scarring and neovascularization. HSV keratitis can be associated with ocular pain and subsequent neutrophic keratopathy. Host cell interactions with HSV trigger an inflammatory cascade responsible not only for clearance of virus but also for progressive corneal opacification due to inflammatory cell infiltrate, angiogenesis, and corneal nerve loss. Current antiviral therapies target viral replication to decrease disease duration, severity and recurrence, but there are limitations to these agents. Therapies directed towards viral entry into cells, protein synthesis, inflammatory cytokines and vascular endothelial growth factor pathways in animal models represent promising new approaches to the treatment of recurrent HSV keratitis.