SBIR-STTR Award

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.!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, and 1 in 2,000 Americans affected by keratoconus. Since many corneal diseases can only be distinguished at the micrometer scale, there is a strong need for imaging tools that can noninvasively visualize the cellular changes in the cornea in vivo, to assist clinical diagnosis, evaluate progression of diseases, and treatment. We have developed a 3D high-definition imaging instrument based on Gabor-Domain Optical Coherence Microscopy (GD-OCM) for noninvasive visualization and quantitative characterization of the cornea over a large field of view. Our data suggest that GD-OCM has the following key advantages over existing in vivo corneal imaging techniques, which include optical coherence tomography (OCT) and confocal microscopy: 1) 6-10x increase in field of view compared to existing confocal microscopes used in clinics worldwide – this will lead to more accurate qualification of the corneal tissue, since a larger area can be assessed; 2) non-contact operation, unlike confocal microscopes, greatly reducing patient discomfort and eliminating risks of corneal damage; 3) high-definition cross-sectional imaging at an order of magnitude better lateral resolution than OCT; 4) 3D imaging capability at the cellular level over the entire thickness of the cornea– this will enable advances in understanding the progression of the diseases. We hypothesize that GD-OCM can accurately conduct all the assessments currently performed with OCT and confocal microscopy, and additionally provide 3D visualization of the cornea structures over the full depth of the cornea for additional tissue characterization and diagnostic aid. In addition to aiding early diagnosis of corneal disease, the proposed GD-OCM instrument will aid in pre- and post-operative screening for refractive surgery, transplant, drug therapies, monitoring wound healing, corneal nerve assessment, and prevention of stromal rejection. 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 and/or insufficient resolution. We propose to commercialize a Gabor-domain optical coherence microscope to enable non-invasive, high-definition, wide field of view imaging in 3D for clinical applications.

Project Terms:
3-Dimensional; accurate diagnosis; Address; Affect; aged; aging population; American; Anterior eyeball segment structure; Area; base; Bilateral; Blindness; Cellular Structures; Clinic; clinical application; clinical Diagnosis; clinical imaging; computer science; Computer software; Confocal Microscopy; Cornea; Corneal Diseases; cost; Data; Diabetes Mellitus; Diagnostic; Disease; Disease Progression; Doctor of Philosophy; Early Diagnosis; Foundations; Fuchs' Endothelial Dystrophy; Future; Glaucoma; Goals; Grant; Image; image guided; image processing; Imagery; imaging capabilities; Imaging Device; Imaging Techniques; improved; in vivo; Infection; instrument; instrumentation; Keratoconus; Lateral; Methods; Microscope; Microscopic; microscopic imaging; Microscopy; Monitor; multidisciplinary; Nerve; non-invasive imaging; operation; Operative Surgical Procedures; Ophthalmology; Optical Coherence Tomography; Optics; Pathology; Patient imaging; Patients; Pharmacotherapy; Phase; Physicians; Play; Postoperative Period; Prevalence; Prevention; Resolution; Retinal; Risk; Role; Scanning; Scheme; screening; signal processing; Small Business Innovation Research Grant; Speed; standard of care; Structure; System; Technology; Thick; Three-Dimensional Imaging; Time; Tissues; Transplantation; United States; Visual; Visual system structure; Visually Impaired Persons; Width; Work; Wound Healing

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 secondmajor cause of blindness in developing countries. There are nearly 5 million bilaterally corneal blind personsworldwide, and an estimated 23 million people affected by unilateral corneal blindness globally. In a conservativeestimate, corneal diseases affect nearly 300,000 people in the United States, with Fuchs' dystrophy affecting4% of people aged over 40. Given the large prevalence of corneal disease and the near-impossibility ofperforming biopsy, high-definition corneal imaging is needed to assist clinical diagnosis, evaluate progression ofdiseases, and treatment. Additionally, the cornea is the most commonly transplanted tissue worldwide.Gabor-domain optical coherence microscopy (GDOCM) is a high-resolution, non-invasive imaging technologythat can visualize microscopic structures in vivo in 3D. Preliminary data suggest that GDOCM has the followingkey advantages over existing corneal imaging techniques, which include specular and confocal microscopy: 1)10-100x increase in field of view - this will lead to more accurate qualification of the corneal tissue, since a largerarea 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 evaluationin one instrument; 3) 3D imaging capability at the cellular level of the mosaic of translucent corneal cells - thiswill enable a detailed understanding the volumetric progression of the diseases.We have assembled an exceptionally strong team of clinical investigators to collaborate on this proposal, andwith their help we have identified four use cases for clinical application of our dual-imaging technology to imagethe cornea with volumetric cellular-resolution. We envision that in the future the dual OCT (optical coherencetomography) and GDOCM instrument enabled by this Phase II SBIR proposal will provide an image-guidancemethod to assist clinicians in the assessment and treatment of corneal diseases and other diseases affectingthe 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 lack the capability to visualize cellular structures in 3D. We propose to commercialize a dual-mode optical coherence tomography and Gabor-domain optical coherence microscopy imaging system to enable non-invasive, high-definition, wide field of view imaging of the cornea in 3D for clinical applications.

Project Terms:
<3-D Imaging><3D imaging>

<3-D visualization><3-dimensional visualization><3D visualization><3-Dimensional><3-D><3D>