Purchase this article with an account.
Cecilia S Lee, Aaron Y Lee, Lakshmi Akileswaran, David W Stroman, Kathryn Najafi-Tagol, Steve Kleiboeker, Anna Wald, Russell N Van Gelder; The Evaluation of Worldwide Distribution of Adenoviral Genotypes in Acute/Epidemic Keratoconjunctivitis and Adenoviral-negative Keratoconjunctivitis with Next Generation Sequencing. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3864. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Conjunctivitis is among the most common outpatient conditions and causes significant ocular morbidity worldwide. The most severe and common form of viral conjunctivitis is epidemic keratoconjunctivitis (EKC), caused by certain strains of adenovirus (Ad). However, the geographic distribution of other Ad genotypes and the role of the ocular surface microbiome (OSM) in EKC have not been established. We investigated the worldwide distribution of Ad genotypes and the OSM associated with keratoconjunctivitis (KC).
A variety of analyses were conducted on samples obtained in a large international clinical trial (NV-422 Phase IIB, NovaBay Pharmaceuticals, Inc). The inclusion criteria were clinical signs and symptoms consistent with KC and evidence of Ad using the rapid screening test (Rapid Pathogen Screening Inc., Saratosa, FL). Bilateral conjunctival swabs were obtained on day 1, 3, 6, 11, and 18. Ad genotype was determined by sequencing of Ad hexon gene (ViraCor-IBT Laboratories, Inc, Lee’s Summit, MO) and the OSM was assessed using next generation sequencing (NGS) on selected samples. The difference in the distribution of Ad genotypes was assessed with Fisher exact.
Overall, 5000 samples were collected from 500 patients. 111, 200, 84, and 103 patients were recruited from US, India, Sri Lanka, and Brazil, respectively. Mean age was 35 and 58% were men. The most common Ad subgenera were subgroup D (316, 63%), followed by E, B, then C. A significant portion of patients (110, 22%) lacked PCR evidence of Ad infection. There was a significant geographic bias for Ad subgenera and serotype distribution (Fisher exact, p-value <10-6). The odds ratio (OR) of having serotype 4 vs. others in the US was 7.87 times higher than in non-US sites (95%CI 3.55, 17.35), while the OR of having serotype 8 vs. others in the US was significantly lower (0.01, 95%CI 0.003, 0.043). Among the samples that underwent NGS, Ad was the dominant virus in 10 of 16 Ad-positive samples, while there was no consistent, dominant virus in 16 Ad-negative samples. Two Ad-negative samples contained significant amounts of torque teno virus.
This study reveals unexpected geographic diversity in Ad genotypes associated with KC, and suggests that nearly one fourth of apparently viral KC may be due to agents other than adenovirus..
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only