SBIR-STTR Award

?As the population continues to age, degenerative ocular diseases become increasingly common and create tremendous burden on the health care system. Vision impairment in the elderly with amd takes away an average of 5 quality years of life. Age-related macular degeneration (amd) represents a large market with ~2 million patients and another ~8 million people at risk in the u.s. Alone. Approximately, 90% of the amd patients have the "dry" form of the disease. There are no approved treatments for dry amd and, thus it represents a potential high impact, targeted area in medicine. The potential market opportunity has been estimated to be up to $4 billion. A pilot study lead by drs. Merry and dotson from the toronto and oak ridge study of photobiomodulation (torpa) looked at the effect of photobiomodulation (pbm) in the treatment of dry amd. The torpa data for dry amd shows clinically and statistically significant improvement in visual acuity and contrast sensitivit, immediately after treatment for 6 weeks, demonstrating the potential use of pbm in dry- amd. The prospective torpa study combined multiple pre-selected monochromatic wavelengths to stimulate mitochondrial cco function and suppress vegf expression. The study conclusions were that led treatment was a non-invasive, easily administered and safe treatment with no serious adverse events noted. More importantly, the study provides the only 1-year follow-up data of led effectiveness in dry amd. Some gradual loss of clinical benefit was seen in the follow-up to one year, suggesting the need to establish a maintenance dosing schedule and the desire to better understand the underlying cellular benefits. Nevertheless, these findings are the first to demonstrate a statistically significant clinical benefit (f(4,68) = 18.86, p

Public Health Relevance Statement:


Public Health Relevance:
the current grant application addresses a novel non-invasive low level light therapy for the dry form of age-related macular degeneration (amd). As the population continues to age, degenerative ocular diseases become increasingly common and create a tremendous burden on the health care system. There are ~2 million amd patients with severe vision loss and another ~8 million amd patients at risk in the u.s. Alone. There are no approved treatments for dry amd and, thus it represents a potential high impact, targeted area in medicine.

NIH Spending Category:
aging; eye disease and disorders of vision; macular degeneration; neurodegenerative; neurosciences

Project Terms:
acute; address; aftercare; age; age related; age related macular degeneration; aged; animal model; anterior ischemic optic neuropathy; applications grants; area; attenuated; base; bioenergetics; biological systems; blindness; cell death; cell model; cell physiology; cells; cellular targeting; chronic; chronic disease; clinical; clinical application; clinical research; commercialization; complement factor h; contrast sensitivity; cost; cytoprotection; data; design; developed countries; development; diabetic retinopathy; disease; disease progression; dose; drusen; effectiveness; elderly; engineering; etiology; experience; follow-up; foundations; functional disorder; healthcare systems; human; impairment; improved; in vitro; in vivo; induced pluripotent stem cell; inflammation; instrument; irradiation; knockout mice; label; lasers; lead; leber's hereditary optic neuropathy; life; maintenance; marketing; medical; medical device; medicine; member; metabolic; mitochondria; mitochondrial dysfunction; molecular target; mouse model; mus; new therapeutic target; novel; ophthalmologist; oxidative damage; oxidative stress; patient care; patients; pharmacologic substance; phenotype; photobiomodulation; photoreceptors; phototherapy; physiologic pulse; pilot projects; population; preventive; property; prospective; public health relevance; research; resources; restorative treatment; retina; retinal; retinal degeneration; risk; safety; schedule; serious adverse event; small business innovation research grant; testing; therapeutic; transgenic organisms; vascular endothelial growth factors; vision; visual acuity

Diabetes affects over 284 million people worldwide and 20% of diabetic patients develop diabetic macular edema (DME), a significant ocular complication that impairs visual function, eventually leading to blindness if left untreated. For patients with DME, current treatment involves laser photocoagulation surgery and intravitreal anti-VEGF injections, which are invasive and expensive procedures. Photobiomodulation (PBM) therapy consists of exposure to low levels of light radiation to targeted tissues resulting in beneficial effects to mitochondrial output and improvements in clinical outcomes. Dry age-related macular degeneration (AMD) shares overlapping pathology with DME including mitochondrial dysfunction and inflammation leading to significant vision loss. Several pilot studies in Dry AMD, e.g., TORPA I & II, LIGHTSITE I, have shown improvements in both visual and anatomical endpoints following PBM treatment. In the most recent LIGHTSITE I study, clinically and statistically significant improvement in visual acuity and contrast sensitivity, reductions in drusen thickness and drusen volume, and improvements in activities of daily living were observed immediately after PBM treatment. PBM treatment was administered using multiple pre-selected wavelengths to stimulate mitochondrial function and to suppress VEGF expression with the Valeda® Light Delivery System. Valeda is the only commercially approved device (CE mark) for dry AMD treatment. The current SBIR proposal aims to expand the utility of the Valeda treatment into the DME population and conduct a pilot prospective, double-masked clinical trial with LumiThera’s Valeda Light Delivery System, with two top retinal DME centers: Stanford (PI: Drs. Diana Do and Quan Nguyen) and the New York Eye and Ear Infirmary (NYEE, PI: Dr. Richard Rosen). Both centers have experience with the Valeda device, and the Study Specific Aims will establish the magnitude of clinical, anatomical and metabolic benefit of multi-wavelength PBM on 40 DME patients, divided into two groups. Approximately 20 subjects will receive PBM treatment and 20 subjects will receive sham treatment 3x per week for 3 weeks using the Valeda Light Delivery System. Stanford University and NYEE provide top DME research environments to conduct this innovative, exploratory clinical trial. All subjects will be assessed for clinical (visual acuity and contrast sensitivity) and anatomical (OCT and OCT-A imaging) outcomes at baseline and Months (M) 1, 3 and 6 post-treatment. Metabolic outcomes (flavoprotein fluorescence) will be measured after each PBM treatment as well as at M3 and M6 to establish the time course of mitochondrial improvement and long-term duration of effect. The findings will provide the basic safety and scientific foundation for a pivotal trial with a novel non- invasive, non-pharmaceutical therapy for DME.

Public Health Relevance Statement:
NARRATIVE There are approximately 93 million persons worldwide with diabetic retinopathy, and over 20% develop complications with diabetic macular edema (DME), the leading cause of vision loss in diabetic patients. The number of persons with diabetes worldwide is predicted to increase dramatically between now and 2030 as a consequence of the growing frequency of obesity, increased lifespan and improved detection of the disease representing a potential high impact, targeted area in medicine. The current grant application addresses a novel non-invasive, cost- effective, photobiomodulation therapy for DME.

Project Terms:
Activities of Daily Living; Acute; Address; Adult; Affect; Aftercare; Age; age related; aged; Anatomy; Angiography; Applications Grants; Area; base; bevacizumab; Blindness; Chronic; Chronic Disease; Clinical; Clinical assessments; Clinical Data; Clinical Research; Clinical Trials; Complication; Contrast Sensitivity; cost; cost effective; Degenerative Disorder; design; Detection; Devices; Diabetes Mellitus; diabetic; diabetic patient; Diabetic Retinopathy; Disease; Disease Progression; Dose; Drusen; Ear; Environment; Etiology; experience; Exposure to; Eye; Flavoproteins; Fluorescence; Foundations; Frequencies; Image; improved; Inflammation; Injections; innovation; instrument; Label; laser photocoagulation; Left; Light; Light Coagulation; Longevity; macular edema; Masks; Measures; Medical; Medical Device; Medicine; Metabolic; Mitochondria; mitochondrial dysfunction; Molecular Target; New York; Nonexudative age-related macular degeneration; novel; Obesity; Operative Surgical Procedures; Optical Coherence Tomography; Outcome; Outcome Measure; Output; Pathology; Patients; Persons; photobiomodulation; Pilot Projects; Placebos; Population; Preventive; Procedures; prospective; Publishing; Radiation; Randomized Clinical Trials; Reporting; Research; Resources; restorative treatment; Retina; Retinal Edemas; Retreatment; Review Literature; Risk; Safety; Series; Small Business Innovation Research Grant; System; Thick; Time; Tissues; Universities; Vascular Endothelial Growth Factors; Vision; Visual; Visual Acuity; Visual impairment