Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

Labib, Bisant A; Minhas, Bhawanjot K; Chigbu, DeGaulle I

Though many consider adenoviral conjunctivitis a disease of self-limitation, the economic burden on affected individuals, high contagion risk, and potential long-term visual complications require a treatment protocol. Studies have indicated that the inflammatory process affecting the cornea begins in the prodromal period of adenoviral infections, thus questioning the theory of self-limitation and adding a potential factor immediate therapeutic management. 98 Dissemination of HAdV is also a significant health burden particularly in individuals with factors that put them at great risk of morbidity and mortality from adenoviral infection. These individuals include children, elderly, immunocompromised individual, patients with acute Graft versus Host disease, those on immunosuppressants, and so on. Because there are no FDA-approved drugs to treat HAdV infection, eye care providers use multiple pharmaceuticals off-label to manage HAdV ocular infection. Finally, the propensity for latent HAdV to become reactivated and easily transmissible warrants the need for additional research in developing an effective, prophylactic antiviral drug. New treatments under consideration include sialic acid analogs, cold atmospheric plasma (CAP), N-chlorotaurine, and even benzalkonium chloride (BAK). Sialic acid plays a role in initial attachment of fiber knobs in adenoviral virions while facilitating accumulation. 95 Sialic acid analogs have been theorized to block sialic acid-containing glycans which act as cellular receptors as a topical treatment. 95, 99 CAP is of use in dermatological disease and chronic wounds and has demonstrated adenoviral type-dependent antiviral effect that may be of benefit. 100 N-chlorotaurine, an endogenous antimicrobial agent, has been shown to shorten duration of illness and is well tolerated in in vitro and in vivo experiments; however, Phase II clinical trials were prematurely ended due to inability to meet primary and secondary endpoints. 101 These endpoints included clearing of bulbar conjunctiva, eradication of virus from tear film, fellow eye involvement, reduction of SEIs, and clearing of vision. 102 BAK is a commonly found preservative in ophthalmic formulations typically present as 0.01% concentration. Studies prove the effectivity of BAK as an antiviral agent against adenovirus in concentrations higher than 0.1%; however, note the disadvantage of ocular toxicity from the known disinfectant. 103 Future considerations in the management of adenoviral keratoconjunctivitis should require consideration of antisepsis and mitigation of sequelae from the host inflammatory response. Furthermore, special consideration for persistent latent HAdV subtypes and immunocompromised individuals is required. Identification of exact mechanisms that underlie the adaptive immune response in adenoviral infections is prudent to the development of novel therapeutic sources. However, the lack of animal models that accurately mimic complexity of human ocular anatomy while also illustrating proper replication and infection of human adenoviruses can prove decelerating for new discovery. 95 Table 2 highlights the efficacy and adverse effects of antiviral and anti-inflammatory agents discussed in this review. 2, 46, 55, 63, 64, 66, 69, 87, In summary, there are several challenges regarding the treatment of adenoviral keratoconjunctivitis. Though there are solutions to some Cidofovir Antiviral activity against HAdV5 exhibited in animal models. 105 Cid