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.

Keywords: Acyclovir; Antiviral; Dendritic keratitis; HSV keratitis; Herpes simplex virus; Host cell; Inflammation; Stromal keratitis.

Figure 1.

Clinical slit lamp photograph of a patient with HSV epithelial keratitis demonstrating a dendrite with branching lesions and terminal bulbs seen with fluorescein staining. (Image courtesy of Dr. Joel Sugar and Dr. Julie Goldman)

Figure 2.

Clinical slit lamp photograph of a patient with HSV necrotizing stromal keratitis showing fulminant necrosis of the corneal stroma with epithelial ulceration. (Image courtesy of Dr. Joel Sugar)

Figure 3.

Clinical slit lamp photograph of a patient with history of HSV stromal keratitis who presented several years after last flare of keratitis with active HSV uveitis with large granulomatous keratic precipitates on the endothelium. (Image courtesy of Dr. Joel Sugar)

Figure 4.

Timeline of clinical course and pathogenesis of HSV keratitis.