Pathobiology and treatment of viral keratitis

Abstract

Keratitis is one of the most prevalent ocular diseases manifested by partial or total loss of vision. Amongst infectious (viz., microbes including bacteria, fungi, amebae, and viruses) and non-infectious (viz., eye trauma, chemical exposure, and ultraviolet exposure, contact lens) risk factors, viral keratitis has been demonstrated as one of the leading causes of corneal opacity. While many viruses have been shown to cause keratitis (such as rhabdoviruses, coxsackieviruses, etc.), herpesviruses are the predominant etiologic agent of viral keratitis. This chapter will summarize current knowledge on the prevalence, diagnosis, and pathobiology of viral keratitis. Virus-mediated immunomodulation of host innate and adaptive immune components is critical for viral persistence, and dysfunctional immune responses may cause destruction of ocular tissues leading to keratitis. Immunosuppressed or immunocompromised individuals may display recurring disease with pronounced severity. Early diagnosis of viral keratitis is beneficial for disease management and response to treatment. Finally, we have discussed current and emerging therapies to treat viral keratitis.

Keywords: Antiviral drugs; Host-virus interaction; Human herpesvirus; Inflammation; Ocular infection; Viral keratitis.

Figure 1.

Representative keratitis pictures of human eyes. (a) Fluorescein stained images of herpes simplex corneal keratitis (Azher et al. 2017). (b) A close-up whole eye image of human eye showing herpetic disciform keratitis (Vislisel. 2015). (c) Varicella zoster virus disciform keratitis (Vislisel. 2014). (d) Slit-lamp imaging of adenoviral keratitis (Wikipedia. 2020). (e) Image of a human eye with fungal keratitis caused due to Aspergillus (Vislisel. 2016). (f) Slit-lamp photography of Nocardia keratitis caused by Nocardia farcinia (Scruggs. 2017).

Figure 2.

HSV-1 life cycle and associated immune reactions during ocular infection. During the primary infection in the corneal epithelium, antigen-presenting cells such as dendritic cells activate the humoral and cellular immune pathways. Naïve T cells and NK cells become activated and target infected host cells for lysis. Likewise, B cells become activated and differentiate into memory B cells and plasma cells. Plasma B cells secrete antiviral antibodies to combat infection. Memory B and T cells remain at the site of latency to monitor reactivation and stimulate a quicker immune response once reactivation is triggered Immune infiltration in the corneal epithelium during recurrent infection creates inflammation, and chronic corneal inflammation can stimulate the development of keratitis.

Figure 3.

Model of HSV-1 infection and reactivation from latency to cause keratitis. Upon the initial infection of the corneal epithelium, the virus travels to the sensory ganglia to establish latency. Upon reactivation, it travels in a retrograde manner back to the eye. The resulting inflammation and immune infiltration in the cornea can lead to keratitis. Other viruses and the corneal layers at which they have been shown to cause keratitis are shown at the bottom of the figure (Gueudry et al. 2013, Holland and Schwartz. 1999, Inoue, Tomoyuki et al. 2010, Lim et al. 2014, Madhavan et al. 2002, Matoba, Alice Y. et al. 1986, Oka et al. 2015, Vislisel. 2014).

Figure 4:

Flow chart showing a generic process to differentially diagnose viral keratitis from other types of ocular inflammatory diseases.