Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

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

Antiviral activity against systemic HAdV infections has been thoroughly studied and paved the way for its more focused evaluation for the treatment of the ocular manifestations of this virus. Besides the aforementioned forms of keratoconjunctivitis, HAdV may also cause upper and lower respiratory tract disease, hemorrhagic cystitis, and gastroenteritis due to its propensity to infect mucosal epithelium. 3, 41, 42 Respiratory infection is typically mild and self-limiting in immunocompetent individuals, but in rare cases, severe respiratory infection and pneumonia may result in acute respiratory distress syndrome (ARDS). Additionally, in immunocompromised patients undergoing hematopoietic stem cell or solid organ transplantation, disseminated infections can be life-threatening, particularly in the pediatric population. 3 Despite thorough investigation on the role of antiviral treatment both systemically and topically, there remains no standard of care. Possible therapeutic benefits have been demonstrated through the use of antiviral drugs such as ganciclovir, ribavirin, and cidofovir. [41] [42] [43] [44] Ganciclovir (GCV), a synthetic nucleoside analog of 2ʹ-deoxyguanosine, has been proven effective in the inhibition of the herpes family of viruses, specifically herpes simplex types 1 and 2, varicella-zoster virus, cytomegalovirus, and Epstein-Barr. In a series of experiments utilizing Syrian, immunocompromised hamsters infected with HAdV 5, GCV was able to suppress viral replication in the liver, a method that may involve the direct inhibition of DNA polymerase. It was proposed that GCV inhibited the advancement of viral infection into the late phase. Systemically, GCV was able to mitigate the effects of HAdV infection in these hamsters, decreasing the rate of mortality. This led to the investigation of GCV in the treatment of ocular infections of HAdV. 43, 44 The ophthalmic gel form (ganciclovir 0.15%, Virgan ® ; Farmila-Thea, Milan, Italy) has been the standard of care for the treatment of acute ocular herpetic keratitis, yet it has not been standardized in the management of adenoviral keratoconjunctivitis, particularly since studies in human subjects are lacking. 43, 44 Current research suggests, however, that with off-label topical use, GCV inhibits the replication of HAdV that leads to ocular infection. Several clinical trials have reported its efficacy. [43] [44] [45] [46] In one study, Huang et al investigated the antiviral activity of GCV against HAdV types 3, 4, 8, 19, and 37 using polymerase chain reaction (PCR) and concluded that there was a significant, dose-dependent inhibitory effect on those serotypes responsible for EKC. 46 Systemically, Bruno et al described the potential therapeutic effect of GCV in that the incidence of HAdV infections was significantly reduced in stem cell-transplant patients treated with GCV for human cytomegalovirus prophylaxis. 45 Sun et al conducted a study utilizing a series of eye drops to treat active EKC infections, including GCV ophthalmic gel, interferon eye drops, a tobramycin-dexamethasone combo, and topical diclofenac sodium. In this study, interferon was administered with the purpose of inhibiting viral replication, while GCV was used for its antiviral properties. To improve efficacy and limit potential ocular side effects, such as inflammation, congestion, and edema, tobramycindexamethasone and diclofenac sodium treatments were also employed. This combination of drugs demonstrated a 91.