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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23EY024921-05
Application #
9603743
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Agarwal, Neeraj
Project Start
2014-12-01
Project End
2019-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Washington
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Ching Wen Ho, Dawn; Agarwal, Aniruddha; Lee, Cecilia S et al. (2018) A Review of the Role of Intravitreal Corticosteroids as an Adjuvant to Antibiotics in Infectious Endophthalmitis. Ocul Immunol Inflamm 26:461-468
Lee, Cecilia S; Larson, Eric B; Gibbons, Laura E et al. (2018) Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease. Alzheimers Dement :
Pepple, Kathryn L; Nguyen, Macklin H; Pakzad-Vaezi, Kaivon et al. (2018) RESPONSE OF INFLAMMATORY CYSTOID MACULAR EDEMA TO TREATMENT USING ORAL ACETAZOLAMIDE. Retina :
Lee, Cecilia S; Kim, Alisa J; Baughman, Douglas et al. (2018) VISUAL ACUITY IMPROVEMENT WHEN SWITCHING FROM RANIBIZUMAB TO AFLIBERCEPT IS NOT SUSTAINED. Retina 38:951-956
Lee, Cecilia S; Lee, Aaron Y; Akileswaran, Lakshmi et al. (2018) Determinants of Outcomes of Adenoviral Keratoconjunctivitis. Ophthalmology 125:1344-1353
Lee, Aaron Y; Lee, Cecilia S; Pieters, Matthew et al. (2018) Differences in Tertiary Glaucoma Care in the Veterans Affairs Health Care System. JAMA Ophthalmol 136:1227-1234
Balaratnasingam, Chandrakumar; An, Dong; Sakurada, Yoichi et al. (2018) Comparisons Between Histology and Optical Coherence Tomography Angiography of the Periarterial Capillary-Free Zone. Am J Ophthalmol 189:55-64
Lee, Aaron Y; Butt, Thomas; Chew, Emily et al. (2018) Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data. Br J Ophthalmol 102:465-472
Zhang, Qinqin; Zhang, Anqi; Lee, Cecilia S et al. (2017) Projection artifact removal improves visualization and quantitation of macular neovascularization imaged by optical coherence tomography angiography. Ophthalmol Retina 1:124-136
Lee, Cecilia S; Baughman, Doug M; Lee, Aaron Y (2017) Deep learning is effective for the classification of OCT images of normal versus Age-related Macular Degeneration. Ophthalmol Retina 1:322-327

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