The 2013-2016 Western African outbreak of the Ebola virus disease (EVD), the largest recorded outbreak since the discovery of Ebola virus (EBOV) in 1976, destabilized local health systems and left thousands of survivors at risk for post-acute sequelae, including vision-threatening uveitis. In an EVD survivor with severe panuveitis, the detection of persistent EBOV in the aqueous humor, long after clearance of acute viremia, focused clinical and research attention on the host-EBOV interaction in the unique terrain of ocular immune-privilege. Despite the recognition that uveitis is common and consequential in EVD survivors, our understanding of pathogenesis is extremely limited, including the contributions of viral persistence and ocular-specific and systemic immune responses to disease expression.

In this study protocol, we outline a multifaceted approach to characterize EVD-associated intraocular inflammation (EVD-IOI), including the clinical phenotype and complications; the presence of EBOV (or EBOV RNA/antigen) in ocular fluids and tissues; and associated local ocular-specific and peripheral immune responses. We utilize an observational cohort design, which includes EVD survivors and close contacts of EVD survivors (i.e., no documented history of EVD), and we propose disease (clinical examination and imaging), as well as molecular, virologic and immunologic characterization, to meet research objectives. Comprehensive findings emerging from the research will inform local stakeholders and global partners to understand and effectively address the individual and public health implications of EVD-associated uveitis, including to optimize clinical decision-making and medical intervention, identify potential ocular and peripheral biomarkers of viral persistence and ocular disease, and ensure effective infection prevention and control.

The authors have declared no competing interest.

This project was supported by the National Eye Institute of the National Institutes of Health under award number R01 EY029594 (Steven Yeh) and K23 EY030158 (Jessica Shantha). Work on this project has also been partially funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024 (Ian Crozier). The content is solely the responsibility of the authors and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.. Funding support is also provided by the Macula Society, the Retina Society, Association for Research in Vision and Ophthalmology, and the Stanley M. Truhlsen Family Foundation, Inc. The opinions, interpretations, conclusions, and recommendations presented are those of the author and are not necessarily endorsed by the U.S. Army.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of University of Nebraska Medical Center gave ethical approval for this work. Ethics committee/IRB of Emory University School of Medicine gave ethical approval for this work. The Ministry of Health Office of Ethics Approval in Sierra Leone gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors