Correlation of Clinical Outcomes and Molecular Epidemiology of Adenoviral Keratoconjunctivitis

Purpose: Adenoviral acute or epidemic keratoconjunctivitis (KC) is a common cause of ocular morbidity worldwide. The purpose of the study is to define the various species and types that exist in KC in correlation with the clinical presentations and outcomes with each species, and investigate the factors that predict poor clinical outcome in KC. Methods: The clinical and molecular data from a randomized, controlled, masked trial for keratoconjunctivitis (NV-422 Phase IIB, NovaBay) were used in the study. In brief, 500 patients from United States, India, Brazil, and Sri Lanka with clinical diagnosis of KC and positive rapid testing for adenovirus (AdV) were included in the study. Clinical signs and symptoms and bilateral conjunctival swabs were obtained on day 1, 3, 6, 11, and 18. PCR was performed to detect and quantify AdV in all conjunctival samples. The difference in composite scores of clinical signs and symptoms between day 1 and day 18 were evaluated by adenoviral species using ANOVA. Time to resolution of each symptom or sign were assessed by adenoviral species with Cox regression. Results: Out of 500 patients, only 390 (78%) had evidence of AdV infection on PCR. Among AdV positive patients, AdV-D was most common (63%) but a total of 4 species and 21 different types of AdV were detected. The mean difference in composite scores of signs and symptoms between day 1 and 18 was significantly different by AdV species (p=0.003, p=0.0009, respectively). The hazard for resolution of lid edema (HR 0.41, adj.p=0.009), bulbar conjunctival injection (HR 0.55, adj.p=0.009), abnormal tear meniscus (HR 0.56, p=0.007), tearing (HR 0.54, adj p<0.006), and photophobia (HR 0.54, adj.p=0.04) were significantly lower in AdV-D group compared to non-D group. The improvement of visual acuity on day 18 was less in patients who started with better initial visual acuity, developed subepithelial infiltrates, and originated from countries other than US. Conclusion: AdV-D infection related signs and symptoms are significantly more severe and less likely to resolve. Identifying patients infected AdV-D at early stage may have clinical implications in providing appropriate therapy and prognosis.