Mystery eye: Human adenovirus and the enigma of epidemic keratoconjunctivitis

• Published in: Progress in retinal and eye research Vol. 76; p. 100826
• Main Authors: Jonas, Rahul A., Ung, Lawson, Rajaiya, Jaya, Chodosh, James
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2020
• Subjects: Adaptive immunity; Adenovirus Infections, Human - epidemiology; Adenovirus Infections, Human - virology; Adenoviruses, Human; Conjunctiva - virology; Cornea - virology; Epidemic keratoconjunctivitis; Epidemics; Eye Infections, Viral - epidemiology; Eye Infections, Viral - virology; Global Health; Human adenovirus; Humans; Innate immunity; Keratoconjunctivitis - epidemiology; Keratoconjunctivitis - virology; Subepithelial infiltrates; Subepithelial infiltrates; Innate immunity; Adaptive immunity; Epidemic keratoconjunctivitis; Human adenovirus
• ISSN: 1350-9462; 1873-1635; 1873-1635
• DOI: 10.1016/j.preteyeres.2019.100826

Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis in which the cornea is also involved, likely due to the specific corneal epithelial tropism of its causative viral agents. The initial development of a punctate or geographic epithelial keratitis may herald the later formation of stromal keratitis, and manifest as subepithelial infiltrates which often persist or recur for months to years after the acute infection has resolved. The chronic keratitis in EKC is associated with foreign body sensation, photophobia, glare, and reduced vision. However, over a century since the first clinical descriptions of EKC, and over 60 years since the first causative agent, human adenovirus type 8, was identified, our understanding of this disorder remains limited. This is underscored by a current lack of effective diagnostic tools and treatments. In part, stasis in our knowledge base has been encouraged by the continued acceptance, and indeed propagation of, inaccurate paradigms pertaining to disease etiology and pathogenesis, particularly with regard to mechanisms of innate and adaptive immunity within the cornea. Owing to its often persistent and medically refractory visual sequelae, reconsideration of key aspects of EKC disease biology is warranted to identify new treatment targets to curb its worldwide socioeconomic burden. •Epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection.•EKC causes conjunctivitis of varying severity, but its hallmark is relapsing and remitting corneal inflammation.•Human adenoviruses, particularly species D, are the main pathogens.•Models of adenovirus keratitis suggest corneal cells play a key role in the host inflammatory response.•To date, only topical corticosteroids and tacrolimus appear to alter the course of chronic keratitis following EKC.