Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions

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

Corneal involvement in EKC occurs in approximately 80% of cases, varying in presentation as a superficial punctate keratitis, focal epithelial punctate keratitis, subepithelial infiltrate (SEI) formation, and reduced corneal sensitivity. 1,2,12,61 SEIs specifically will often manifest anywhere from one to three weeks following the acute phase of the infection. Histologically they are comprised of residual antigen and lymphocytic accumulations that adhere to stromal cells in the cornea. 62 This clinical finding may persist for months to years following resolution of the conjunctivitis, leading to subjective visual disturbances, such as decreased vision, photophobia, halos, and the development of irregular astigmatism. Due to their chronicity and visual impact, treatments including anti-inflammatory and immunosuppressive agents have been investigated to treat as well as prevent SEIs, though they often end up resolving without scarring or corneal neovascularization formation. 2, 12, 62 Research demonstrates that mild corticosteroid treatment administered topically approximately three times per day can significantly improve EKC symptoms and, if used in the short term, acute phase of the disease, does not lead to significant ocular side effects. There is also additional benefit in the use of topical corticosteroids once the acute phase of the infection resolves, for the remaining, persistent SEIs. 2, 63 While chronic corticosteroid treatment has been proven to reduce these findings, a significant challenge to this mode of treatment is the risk of complications of long-term use, including glaucoma and cataract formation. [64] [65] [66] [67] [68] [69] Additionally, corticosteroid treatment of SEIs can result in a 17.5% recurrence rate and consequential, unsuccessful drug tapering. 70 If discontinued abruptly, these viral antigens continue to attract lymphocytes, causing persistence of SEIs. 62, 66 Excimer laser ablation can be helpful in such cases. 63 In a study comparing topical loteprednol with dexamethasone, similar outcomes in SEI treatment were observed. This is significant because milder topical steroid forms, such as loteprednol, are known to have less risk of adverse effects. 71 However, it is important to note that short-term treatment with topical steroids of limited potency may also delay viral clearance. 72 Nonsteroidal anti-inflammatory drugs (NSAIDs) are another alternative to corticosteroids, in that they are approved for topical, ocular use and exhibit antiinflammatory effects without the substantial risk of glaucoma and cataract effect seen with steroid use. These agents work on the arachidonic acid pathway by inhibiting cyclooxygenase and, subsequently, the formation of prostaglandins, thromboxane, and prostacyclin. With specificity to ocular uses, they have been shown to be effective in cases of allergic conjunctivitis, alkali burns, herpetic uveitis, ocular trauma, and pre/post-operative cataract and refractive surgeries. 73- 76 Gordon et al were the first to investigate NSAID effects on adenoviral replication, specifically ketorolac tromethamine and diclofenac sodium ophthalmic solutions. During both the early and late phases of infection, the effect of NSAIDs on viral titers did not differ from control groups, nor did it affect the duration of viral shedding. In contrast, prednisolone treatment was shown to prolong viral shedding. 73 As it pertained to sub-epithelial infiltrates, treatment with diclofenac or ketorolac di