Clinical and molecular biomarker surveillance in Mpox-related ocular disease

Project Summary / Abstract The ongoing mpox outbreak was declared a WHO Public Health Emergency of International Concern (PHEIC) in 2022-2023, and a second PHEIC was declared in August 2024 due to the escalation of cases in Central and Eastern Africa. Most recently, cases of mpox have emerged in the United States, the United Kingdom, Canada, India and Thailand, with increased risk of international spread. During the initial PHEIC, reports of keratitis associated with mpox clade II were reported, including cases of severe vision loss and viral persistence. Clade II mpox within West Africa have also escalated, heightening concerns about travel-related cases. Viral identification within the tear film has raised questions about its contribution to ophthalmic disease. Within 2025, cases of both clade I and II mpox have escalated, leading to questions about human- to-human transmission and disease morbidity. Prior reports have suggested that clade I mpox virus infection may be associated with a higher rate of ocular complications than clade II mpox, but the true prevalence and vision impact are unknown. These findings have prompted urgent questions about the epidemiology of disease, the spectrum of ophthalmic manifestations, viral kinetics within the tear film, and the ocular immune response. To fully characterize the ocular findings of mpox, we propose the following Specific Aims. In Aim 1, we seek to understand the ophthalmic disease epidemiology, spectrum of ocular manifestations, focusing on keratitis, conjunctivitis and uveitis in mpox clade I compared to clade II infection. We will also identify risk factors for ocular disease to inform public health interventions for patients and the international community. In Aim 2, we plan to assess the kinetics of mpox DNA tear film clearance following acute infection. Given the observations that mpox may persist within the tear film, understanding the kinetics of clearance is highly relevant to patients and the public. We will also assess the local immune response of patients with mpox with ocular disease to determine the pathologic and protective responses that may inform biomarker identification. This comprehensive approach to understanding ophthalmic disease associated with mpox within countries where the highest mpox caseloads have been observed will provide timely information for the United States and global community. Insights into disease prevalence, clinical findings, ocular surface viral clearance, and immune responses will prevent and treat sight-threatening eye disease associated with mpox. An improved understanding of pathobiology and the biomarkers identified will inform management for Americans and individuals affected by mpox globally.