DESCRIPTION (provided by applicant): Ocular infectious diseases such as endophthalmitis and conjunctivitis remain a significant cause of visual morbidity and potential blindness. However, traditional microbial cultures often fail to identify causative organisms in a high proportion of clinically suspicious infections. Most pathogens responsible for ocular infections originate from the ocular surface. Thus, characterizing the ocular surface microbiome in different disease states may lead to a better understanding of the pathogenesis of these conditions. Our goal is to understand the community structure of ocular surface microbial flora that predisposes the eye to infection and influences various disease courses. Our overarching hypothesis is that the constituents of the ocular surface microbiome are involved in the pathogenesis of potentially infectious ophthalmic conditions. To explore this hypothesis, we propose to study the ocular surface microbiome, in particular a recently described virus, torque teno virus (TTV), in three diseases by using a novel, deep DNA sequencing technique. In specific aim 1, we propose one prospective and one retrospective study to determine the correlation between the ocular surface microbiome and clinical outcomes of epidemic keratoconjunctivitis and endophthalmitis. In specific aim 2, we propose a randomized clinical trial to study the ocular surface microbiome and its relationship to the treatment outcome in patients with dry eye syndrome. My ultimate career goal is to become an independent physician-scientist in the field of ophthalmology. I am committed to developing a clinical research-oriented career in major academic institutions and understand the need for me to pursue additional training and mentorship. During the Mentored Research Career Development Award period, I plan to obtain a Master of Science in Epidemiology (Clinical Research Track) and participate in several, focused didactic coursework in microbiology, fundamentals of clinical research, and molecular diagnostics. The additional training, research experience, and most importantly, mentorship by committed experts will be of uttermost importance in becoming a successful clinician-researcher.

PUBLIC HEALTH RELEVANCE: Many serious ocular diseases are presumed to be infectious, yet traditional microbial cultures fail to identify a pathogen in a high proportion of cases. The most likely origin for these organisms is the ocular surface. Thus, the constituents of the ocular surface microbiome likely influence the pathogenesis and the outcomes of these important conditions. We propose to use a new representational deep DNA sequencing technique that allows for an unprecedented analysis of the ocular surface and intraocular microbiome in order to characterize the ocular surface microbiome in epidemic keratoconjunctivitis, endophthalmitis, and dry eye syndrome and determine its association to overall disease outcomes.