Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

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

Topical cyclosporine (both 1% and 2% concentrations) is an alternative option which, if used in the acute phase of adenoviral keratoconjunctivitis, is successful in both reducing the risk of developing corneal findings as well as the chronic treatment of persistent SEIs, with most cases resolving over a course of 3-4 weeks. 64, 66, 69, 78 Okumus et al studied the efficacy of 0.05% cyclosporine (Restasis ® , Allergan, Irvine, California, USA) once per day or once every other day, in treatment of SEIs secondary to adenoviral epidemic keratoconjunctivitis in cases persisting for more than three months. Patients in this study had also initially been treated with topical corticosteroids for several months with no regression, or who had to discontinue due to subsequent, elevated IOP. After one month of 0.05% cyclosporine treatment, 81.75% of eyes had cleared SEIs while the remaining 18.2% had decreased in number. No systemic or ocular side effects were observed. Few cases (11.12%) in this study resulted in recurrence of SEIs after discontinuing treatment. 69 Cyclosporine is likely effective in these cases due to its action in the inhibition of T cell proliferation and activation, thereby reducing ocular surface inflammation. 77 It has been shown to be efficacious in various ocular diseases, such as vernal keratoconjunctivitis, ulcerative keratitis, Thygeson superficial punctate keratitis, herpes stromal keratitis, dry eye disease, superior limbic keratoconjunctivitis, and many others. 69, [79] [80] [81] Asena et al also evaluated treatment options for acute adenoviral keratoconjunctivitis using either topical 1% prednisolone acetate in conjunction with non-preserved artificial tears, topical 2% Cyclosporine A with non-preserved artificial tears, or non-preserved artificial tears alone. In comparison to artificial tears alone, both the corticosteroid and cyclosporine groups exhibited improvement in symptoms as well as a shorter duration. Both the Cyclosporine A and prednisolone groups were also similarly effective in preventing the development of SEIs when used during the active phase of infection, suggesting possible prophylactic benefit. 72 Tacrolimus is another immunosuppressive agent that also demonstrates anti-inflammatory activity. Like cyclosporine, tacrolimus' initial use was to prevent rejection in organ transplants. However, despite similar effects, tacrolimus and cyclosporine differ in their chemical makeup. Cyclosporine is a cyclic endecapeptide, in contrast to tacrolimus, which is a macrocyclic lactone. Both are calcineurin inhibitors, an enzyme necessary for T cell replication. 82, 83 When cyclosporine and tacrolimus enter T cells, they bind to their respective immunophilins, which are important proteins that interact with calcineurin, and inhibit their action. Blocking calcineurin subsequently inhibits the transcription of several cytokines that are necessary to the immune pathway and response, particularly IL-2. This cytokine is integral in the maintenance, differentiation, and survival of CD4 + T cells and CD8 + T cells. 70, [84] [85] [86] Topical tacrolimus 0.03% has ophthalmic uses, mainly in the treatment of giant papillary conjunctivitis and vernal keratoconjunctivitis. With regards to its effect on HAdV keratoconjunctivitis, tacrolimus was more effective than dexamethasone in the reduction of SEIs, and subsequently in the improvement of vision and symptomology. This study is significant in that tacrolimus was not only sup