Spatial Frequency Domain Imaging to Investigate Mechanistic Constituents in Active Thyroid Eye Disease - PROJECT SUMMARY/ABSTRACT Thyroid Eye Disease (TED) is an inflammatory condition that can lead to severe vision problems due to cytokine production, fibroblast activation, and glycosaminoglycan deposition that cause vascular congestion and tissue edema. Insulin-like growth factor 1 (IGF1R) plays a key role in TED's development, impacting endothelial cell migration, fibrosis, and neovascularization; thus, TED patients can be prescribed teprotumumab, an IGF1R inhibitor. However, there is no standardized diagnostic or therapeutic tool for TED, making it crucial to develop rapid imaging methods and quantifiable biomarkers to offer personalized patient care. Spatial Frequency Domain Imaging (SFDI), developed at UCI's Beckman Laser Institute (BLI), is a promising solution. SFDI uses several wavelengths to assess tissue properties (oxy and deoxyhemoglobin, oxygen saturation, as well as absorption and reduced scattering coefficients) up to 5 mm in depth. SFDI has successfully predicted surgical outcomes and treatment responses in other medical conditions. Dr. Ediriwickrema’s research aims are to use SFDI to non-invasively identify optical tissue properties in TED, particularly those related to vascular congestion and tissue edema (Aim 2A), as compared to age-matched controls (Aim 1). She will also establish an optical signature profile for TED patients receiving teprotumumab (Aim 2B). The team will also conduct clinical pathology correlations (CPC 1, 2A, 2B) on surgical specimens from both healthy and TED patients. This K23 proposal provides comprehensive training for Dr. Ediriwickrema and enables her to develop noninvasive diagnostic and therapeutic response metrics for TED and similar inflammatory conditions. Dr. Bernard Choi, a recognized expert in wide-field imaging applications in the characterization and treatment of microvascular-related diseases, will mentor Dr. Ediriwickrema. Secondary mentors, Drs. Anthony Durkin, Anand Ganesan, Krzysztof Palczewski, and Kristen Kelly bring extensive expertise in the development and application of in vivo SFDI techniques, multiphoton microscopy for assessing cutaneous inflammatory changes, and advanced high-resolution molecular imaging techniques, such as 2-photon imaging. Additionally, Drs. Vivek Patel, Vasan Venugopalan, and Maria Estopinal will provide valuable guidance in TED management, optimization of SFDI-derived tissue optical parameters, and histopathologic evaluation of periocular inflammatory disease. Dr. Ediriwickrema will benefit from the rich scientific environment at UCI, including resources in the Department of Ophthalmology, BLIMC, Institute for Clinical and Translational Science (ICTS), Center for Translational Vision Research (CTVR), and Biostatistics Epidemiology and Research Design (BERD) Unit. This K23 training will equip Dr. Ediriwickrema with the skills to apply SFDI effectively to establish objective and continuous optical tissue biomarkers that characterize TED activity and response to treatment, and enable her to become an independent physician-scientist specializing in oculofacial inflammatory diseases.
