Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

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

erior to topical corticosteroids in the resolution of clinical signs and symptoms but also offered a lower recurrence rate and no significant rise in IOP as is sometimes seen with steroid use. Adverse effects were observed in 17.8% of patients using tacrolimus, manifesting as burning, redness, and foreign body sensation. 70 Generally, for SEIs that are resistant to tapering of corticosteroid, tacrolimus 0.03% was proven to be an effective corticosteroid-sparing agent. 87 Another promising treatment for HAdV is adoptive T cell therapy. This involves the transfer of virus-specific T cells into Tcell-depleted patients to fight infection. HAdV-specific T cells are present in peripheral blood of healthy individuals in low frequencies; as a result, donor leukocytes were reportedly useful in patients with severe HAdV infection. HAdV-specific T cells play a significant role in viral clearance, and as such, adoptive transfer of HAdV-specific T cells would be an immunotherapeutic agent of immense benefit for patients at risk of disseminated adenoviral infection. The method of adoptive T cell therapy involves harvested leukocytes that are stimulated and expanded in vitro using peptide-MHC I tetramers, instead of using lymphocytes derived from the same donor as the transplant which yielded results as early as two weeks. 13, 44 This therapy along with antiviral use appears to be synergistic and efficacious. 44 Cardiotonic steroids digoxin and digitoxin have been suggested to offer a new strategy to target and suppress HAdV. Historically, these drugs have been used to treat heart failure for over 200 years. More recently, they have also shown efficacy in cancer treatments, in that treated patients demonstrated a lesser chance of relapse. 88 Hartley et al first noted its potential antiviral benefit, noting its efficacy against HAdV and herpesviruses. 89 This is due to the drugs inhibiting Na+/K+ ATPase on the cell surface, which leads to increased intracellular levels of NA+ and, subsequently, Ca++. Na+/K+ ATPase is an important cell signaling molecule, where binding with digoxin or digitoxin initiates multiple signaling cascades, influencing gene expression. These drugs also alter RNA splicing, which is necessary to HAdV replication. Preliminary data supports a concentration-dependent reduction in the number of infected cells and no apparent damage. Although there is known toxicity, particularly with long-term use of digoxin, the antiviral uses of cardiotonic steroids would be short term, negating the associated systemic complications. As such, these drugs seem to be efficacious against HAdV serotypes A-D and serve as potential treatment therapies for the treatment and prophylaxis of EKC. 88 Thus, repurposing of these cardiotonic steroids as an antiviral agent for short-term treatment of adenoviral keratoconjunctivitis as well as a prophylactic for use in individuals in close contact with patients with epidemic keratoconjunctivitis. 88 Furthermore, Marrugal-Lorenzo et al reported that mifepristone, a synthetic steroid drug, possesses anti-adenoviral properties via its interference with viral entry into the nucleus. As such, it could be repurposed for treating adenoviral infections. 90