Wide-field three-dimensional high-resolution imaging of the cornea - Summary The objective of this project is to investigate groundbreaking approaches for in-vivo high-resolution imaging of fine corneal structures with confocal-like sectioning capability, wide field-of-view (FOV), and polarization and phase sensitive detection. With further development, the proposed technique should be easy to implement and use in a clinical environment while overcoming the limitations of current techniques. Despite remarkable developments and advances in imaging technologies, in particular, by the advent of optical coherence tomography (OCT) that has transformed the diagnosis and management of ophthalmic diseases, the clinical assessment of cellular structures of the cornea remains challenging in patients, while visualization of sub- cellular structures remains beyond reach. While clinical OCT provides a lateral resolution of about 15µm, in-vivo confocal microscopy (IVCM) can achieve much higher (~1µm) lateral resolution. Several issues have prevented the widespread adoption of IVCM for routine cornea imaging in clinical practice, e.g., requiring physical contact with the patient’s cornea and capturing a small FOV. Corneal disorders are among the leading causes of blindness worldwide. Therefore, new methods are needed to better resolve corneal structures in the living human eye in a reliable and consistent fashion. The project will investigate speckle illumination holographic imaging with the additional capability to record the polarization of the optical fields, thus providing information about the anisotropy of the cornea. It will also address the capture of three-dimensional information over the depth and width of the cornea. After a system is developed and optimized, a proof-of-concept validation will be carried out in vivo in healthy adult human volunteers. The proposed imaging approach will facilitate the evaluation of corneal cell and nerve morphology in healthy and pre/post-operative individuals, thus having a substantial impact in the study, prevention, diagnosis, treatment, and monitoring of various corneal diseases. With the cornea serving as a privileged site for the direct visualization and study of numerous general physiologic and pathologic processes, the significance of the results however extends well beyond ophthalmology.