SBIR-STTR Award

?The primary endpoint of this SBIR phase I proposal is to develop a method capable of monitoring retinal oxygen metabolism in patients undergoing treatment for vision-threatening diabetic retinopathy (DR) in the clinical Ophthalmology setting. I is estimated that by the year 2030 over 150 million individuals will suffer from DR worldwide. In its earliest form, DR is characterized by a number of subtle metabolic alterations that form a background environment from which later-stage structural alterations can emerge. If left unchecked, these structural alterations will eventually lead to debilitating vision loss. Although there are a number of treatment options for the vision-threatening stages of DR, the choice of optimal treatment program remains both highly contentious and subjective due in large part to questions of effectiveness, cost, and safety. As a result, there is a need for an accurate and non-invasive platform technology that enables Ophthalmologist's to monitor and respond to changes in treatment efficacy at the earliest time-point possible. Unfortunately, due to a number of technical limitations, current management of DR relies on quantification of later-stage structural markers rather than the more sensitive/early metabolic markers. To address this problem, we invented visible-light optical coherence tomography (vis-OCT), a break-through biophotonic technique that uses the strong absorption of hemoglobin within the visible range of wavelengths to quantify oxygen metabolic markers in the retinal microvasculature. Preliminary simulation and in-vivo animal studies demonstrate the unique capability of using vis-OCT to simultaneously calculate retinal oxygenation, blood flow velocity, and oxygen metabolic rate. In the 6 months of the grant administration, we will development the necessary hardware and software modifications needed to translate vis-OCT from research use only to a product configuration intended for use in the clinical Ophthalmology setting. The project will prove the feasibility of measuring retinal metabolic markers in human subjects. Moreover, it will serve as the stringboard into the next stages of clinical assessment by beginning the work of cataloging 'ideal' baseline metabolic marker values in healthy subjects. The successful completion of the current proposal will enable a phase II SBIR proposal for comprehensive longitudinal studies to assess the magnitude and directionality of metabolic alterations which occur in the early stages following administration of therapy for vision-threatening DR.

Public Health Relevance Statement:


Public Health Relevance:
The optimal treatment program for patients with vision-threatening diabetic retinopathy remains both highly subjective and contentious. We propose to develop a clinically viable visible-light optical coherence tomography (vis-OCT) system to non-invasively quantify the subtle retinal metabolic changes that provide the earliest indication of a patient's response to treatment. We foresee the use of vis-OCT to guide Ophthalmologists' decisions regarding treatment choice, dosage, and timing.

Project Terms:
absorption; Address; Adult; Age-Years; American; Anatomy; angiogenesis; Angiography; Animal Testing; Animals; Anxiety; Appearance; base; bevacizumab; Biophotonics; Blindness; Blood; Blood flow; Blood Flow Velocity; Caliber; Cataloging; Catalogs; Chronic Disease; Clinic; Clinical; Clinical assessments; clinically significant; Computer software; cost; cost effectiveness; Decision Aid; density; Development; Diabetic Retinopathy; dosage; Dose; Environment; ergonomics; Eye; Feedback; Fluorescein; Functional Imaging; Goals; Grant; Health; Healthcare Systems; healthy volunteer; Hemoglobin; Human; human subject; Image; imaging modality; in vivo; Individual; individualized feedback; instrument; instrumentation; intravitreal injection; Ischemia; Knowledge; Lasers; Lead; Left; Legal Blindness; Legal patent; Licensing; Lighting; Longitudinal Studies; Measures; medical attention; Metabolic; Metabolic Marker; metabolic rate; Metabolism; Methods; minimal risk; Modality; Modification; Monitor; Ophthalmologist; Ophthalmology; Optical Coherence Tomography; Oxygen; Patient Monitoring; Patients; Pharmaceutical Preparations; Phase; Physicians; Physiological; Process; prototype; public health relevance; Regulation; Research; response; Retina; Retinal; Retinal Diseases; retinal ischemia; Rodent Model; Safety; Sample Size; Scanning; simulation; Small Business Innovation Research Grant; Specialist; Speed; Staging; standard of care; System; Techniques; Technology; technology development; Testing; Therapeutic; Time; tool; Translating; treatment choice; Treatment Efficacy; treatment planning; treatment program; treatment response; Universities; unnecessary treatment; Ursidae Family; Variant; Vascular Endothelial Growth Factors; Visible Radiation; Vision; volunteer; Work

Diabetic retinopathy (DR) is a complication of diabetes and a leading cause of blindness in the world. Although it is widely accepted that DR is driven by ischemia, the current grading of DR severity is based only on structural alterations such as the presence of abnormal retinal microvasculature in non-proliferative DR or angiogenesis in proliferative DR. As a result, most patients have already developed irreversible retinal functional impairment when they first receive their DR diagnosis. DR develops through progressively increasing capillary non-perfusion leading to insufficient blood supply to meet the metabolic demand of the inner retinal neurons. This causes retinal ischemia, which activates signaling pathways that promote angiogenesis and herald the proliferative phase of retinopathy. If not managed in a timely fashion, proliferative DR can ultimately lead to blindness. Therefore, non-invasive imaging of retinal metabolic rate of oxygen is expected to improve our understanding of DR pathophysiology as well as significantly enhance our ability to diagnose and manage high-risk DR. This proposal aims to maximize the likelihood of translation and integration of a novel visible-light optical coherence tomography or vis-OCT into clinical management of DR. We seek to design, develop, and optimize the first clinical-prototype vis-OCT instrument to quantify retinal metabolic rate of oxygen in normal human subjects as well as in patients with diabetes. We believe that the proposed technology has the potential to transform the existing clinical practice of DR from anatomy-based approach to a more sensitive and objective function-based approach. The proposed work is built on Opticent Health?s successful meeting the goals in the Phase I project and on close collaboration with leading clinician-scientists.

Thesaurus Terms:
Age; Age Related Macular Degeneration; Algorithms; Anatomy; Angiogenesis; Background Diabetic Retinopathy; Base; Bevacizumab; Biological Markers; Blindness; Blood Capillaries; Blood Flow; Caring; Clinical; Clinical Application; Clinical Management; Clinical Practice; Clinical Research; Collaborations; Complications Of Diabetes Mellitus; Data; Design; Development; Diabetes Management; Diabetes Mellitus; Diabetic Retinopathy; Diagnosis; Disease; Engineering; Failure; Feedback; Functional Disability; Functional Disorder; Functional Imaging; Glaucoma; Goals; Health; Hemoglobin; High Risk; Hospitals; Human; Human Subject; Image; Imaging Technology; Improved; Instrument; Intervention; Ischemia; Lasers; Lead; Legal Patent; Licensing; Light Coagulation; Low-Level Laser Therapy; Mathematical Analysis; Measures; Medical Center; Meetings; Metabolic; Metabolic Imaging; Metabolic Rate; Modernization; Monitor; Monitoring For Recurrence; New York; Non-Invasive Imaging; Non-Invasive Monitor; Novel; Ophthalmologist; Ophthalmology; Optical Coherence Tomography; Outcome; Oxygen; Patients; Peripheral; Phase; Photoreceptors; Positioning Attribute; Proliferative Diabetic Retinopathy; Protocols Documentation; Prototype; Recording Of Previous Events; Response; Retina; Retinal; Retinal Detachment; Retinal Diseases; Retinal Imaging; Retinal Ischemia; Retinal Neuron; Retinopathy Of Prematurity; Rodent Model; Role; Scientist; Secure; Severities; Signal Pathway; Structure; Technology; Technology Development; Testing; Time; Tool; Traction; Translations; Universities; Usability; Vascular Blood Supply; Visible Radiation; Vitreous Hemorrhage; Work;