The cornea, the outermost window of our visual system, is vulnerable to various types of infections and diseases. Corneal disease is one of the leading causes of visual deficiency and blindness, and is considered the second major cause of blindness in developing countries. There are nearly 5 million bilaterally corneal blind persons worldwide, and an estimated 23 million people affected by unilateral corneal blindness globally. In a conservative estimate, corneal diseases affect nearly 300,000 people in the United States, with Fuchs dystrophy affecting 4% of people aged over 40. Given the large prevalence of corneal disease and the near-impossibility of performing biopsy, high-definition corneal imaging is needed to assist clinical diagnosis, evaluate progression of diseases, and treatment. Additionally, the cornea is the most commonly transplanted tissue worldwide. In 2012, nearly 185,000 corneal transplants were performed in 116 countries from tissue procured by 742 eye banks, with the US having the highest rate of transplantation. Over one half of the worlds population does not have access to corneal transplantation, resulting in a global shortage of corneal graft tissue, with only 1 available out every 70 corneas needed. Endothelial cells cannot regenerate in vivo, therefore evaluation of their density is a very important measure of corneal health. The shortage of available transplant tissue underscores the importance of reliable, objective methods to evaluate tissue quality at eye banks and ensure accurate selection of corneal grafts that are suitable for transplantation. Approximately 35% of the procured corneas (100,000 corneas annually) end up not being transplanted; according to the Eye Bank Association of America, 40% of the corneas rejected are due to defects noticed during examination. Additionally, around 20% of transplants fail due to rejection of the cornea; thus, effective methods of monitoring reintegration of the tissue into the host are needed. Gabor-domain optical coherence microscopy (GD-OCM) is a high-resolution, non-invasive imaging technology that can visualize microscopic structures in vivo in 3D. Preliminary data suggest that GD-OCM has the following key advantages over existing corneal imaging techniques, which include specular and confocal microscopy: 1) 4-10x increase in field of view this will lead to more accurate qualification of the corneal tissue, since a larger area can be assessed; 2) simultaneous measure of corneal thickness, quantification of endothelial cell density, as well as identification of morphological variations due to corneal disease this will lead to full corneal evaluation in one instrument; 3) 3D imaging capability at the cellular level of the mosaic of translucent corneal cells this will enable a detailed understanding the volumetric progression of the diseases. We envision that in the future the GD-OCM instrument enabled by this Phase I SBIR proposal will provide the early foundation for an image-guidance method to assist clinicians in the assessment and treatment of corneal diseases and other diseases affecting the anterior segment of the eye, including diabetes and glaucoma.
Public Health Relevance Statement: Noninvasive imaging is the holy grail for clinical diagnosis. Current corneal imaging techniques are limited by limited field of view. We propose to commercialize a Gabor- domain optical coherence microscope to enable non-invasive, high-definition, wide field of view imaging in 3D for eye banks and clinical applications.
Project Terms: Affect; aged; Americas; Anterior eyeball segment structure; Aqueous Humor; Area; base; Bilateral; Biopsy; Blindness; Cell Count; Cell Density; Cells; Cellular Morphology; Cellular Structures; Clinic; clinical application; clinical Diagnosis; clinical imaging; commercial application; computer science; Confocal Microscopy; Cornea; Corneal Diseases; corneal epithelium; cost; Country; Data; Defect; density; Developing Countries; Diabetes Mellitus; Diabetic mouse; Diagnosis; Diagnostic; digital imaging; Disease; Disease Management; Disease Progression; Doctor of Philosophy; Effectiveness; Endothelial Cells; Ensure; Evaluation; Eye; Eye Banks; Foundations; Fuchs' Endothelial Dystrophy; Future; Glaucoma; Goals; Gold; Grant; Health; Human; human model; Image; image guided; image processing; Imagery; imaging capabilities; Imaging Device; Imaging Techniques; Imaging technology; improved; in vivo; in vivo evaluation; Infection; instrument; instrumentation; Insulin-Dependent Diabetes Mellitus; Keratoplasty; Measurement; Measures; Methods; Microscope; Microscopic; microscopic imaging; Microscopy; Monitor; Morphology; Mosaicism; mouse model; multidisciplinary; Mus; Natural regeneration; Nerve; Neuropathy; non-invasive imaging; novel; Operative Surgical Procedures; Ophthalmology; Optical Coherence Tomography; Optics; Pathology; Patient Monitoring; Patients; Phase; Population; Postoperative Period; Prevalence; Resolution; Retinal; Sampling; Small Business Innovation Research Grant; standard of care; Structure; Thick; Three-Dimensional Imaging; Time; Tissue Donors; Tissue Grafts; Tissues; Transplantation; Transplanted tissue; United States; Variant; Visual; Visual system structure; Visually Impaired Persons; Work
