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. A investigator study lead by Drs. Merry and Dotson from The Toronto and Oak Ridge Study of Photobiomodulation (TORPA) looked at the effect of low level light therapy (LLLT) in the treatment of dry AMD. The TORPA data for dry AMD shows clinically and statistically significant improvement in visual acuity and contrast sensitivity, immediately after treatment for 6 weeks, demonstrating the potential use of LLLT in dry-AMD. The TORPA study combined multiple pre-selected 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. 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; Bioengineering; Clinical Research; Clinical Trials and Supportive Activities; Eye Disease and Disorders of Vision; Macular Degeneration; Neurodegenerative

Project Terms:
Acute; Address; Aftercare; Age; age related; Age related macular degeneration; Angiography; Anterior Ischemic Optic Neuropathy; Applications Grants; Area; base; biological systems; Blindness; Cells; Chronic; Chronic Disease; Clinical; clinical application; Clinical Data; Clinical Research; Clinical Trials; Code; Color; commercialization; Contrast Sensitivity; cost; Data; design; Developed Countries; Development; Diabetic Retinopathy; Disease; Disease Progression; Dose; Drusen; Effectiveness; Elderly; Engineering; Enrollment; Ensure; Etiology; experience; Exudative age-related macular degeneration; follow-up; Foundations; Healthcare Systems; Human; Image; Impairment; Inflammation; instrument; Label; Lasers; Lead; Leber's Hereditary Optic Neuropathy; Life; macula; Maps; Marketing; Masks; Measurement; Medical; Medical Device; Medicine; member; Metabolic; meter; Mitochondria; mitochondrial dysfunction; Molecular Target; new therapeutic target; novel; Ophthalmologist; Outcome Measure; Oxidative Stress; Patient Recruitments; Patients; photobiomodulation; Phototherapy; Placebos; Population; Preventive; Property; prospective; prototype; public health relevance; Randomized Clinical Trials; Research; Research Personnel; Resources; restorative treatment; Retinal; Risk; Safety; Scanning; Serious Adverse Event; Small Business Innovation Research Grant; Specialist; Staging; Thick; Time; tomography; Treatment Protocols; Universities; Vascular Endothelial Growth Factors; Venous; Vision; Visual Acuity

As the population continues to age, degenerative ocular diseases become increasingly common and create a tremendous burden on the health care system. Age-related macular degeneration (AMD) represents a significant problem with 10-11 million patients at risk to progress to severe vision loss in the U.S. alone and the prevalence of AMD is expected to double by 2020. The dry and wet forms of the disease significantly impair visual function and there are no approved treatments for dry AMD, which affects 85-90% of AMD patients. Photobiomodulation (PBM) is a low level light therapy used to induce beneficial cellular processes resulting in significant clinical outcomes, including tissue repair, tissue regeneration and anti-inflammatory effects. At the cellular level, the mechanisms of PBM are ascribed to activation of mitochondrial respiratory chain components resulting in stabilization of metabolic function. Our previous pilot studies demonstrate improvements in clinical (visual acuity (VA) and contrast sensitivity (CS)), anatomical (drusen volume and thickness) and QoL outcomes in PBM-treated patients with Dry AMD. LumiThera Inc. is a medical device company dedicated to establishing novel treatment therapies for ocular indications. Multi-wavelength LED commercial instruments have been designed and built for an ophthalmologist office-based setting. The current SBIR phase II application is to extend the findings from the SBIR phase I pilot study and conduct a prospective, double-masked, multi-center clinical trial with approximately 192 subjects using LumiThera's ophthalmological designed light delivery system, the LT-300. Discussions with the FDA in a presub meeting have established the trial design and discussed potential expedited clearance routes in the US under the Breakthrough Devices Program Draft Guidance for Industry and Food and Drug Administration Staff. Specific Aims will establish the magnitude of clinical and anatomical outcome benefits of multiple LED wavelengths in dry AMD patients. Subjects with BCVA of 20/32 to 20/80 and no central fovea involvement will be randomized in a 1:2 ratio into sham-treatment or PBM-treatment groups. Subjects will be treated twice during two treatment series within a 9-month long study. A post-marketing annual follow-up reporting period may be included per approval with FDA, separately and could be supported under a phase III NIH program. Each treatment series will consist of PBM or sham treatment 3x/week for 3 weeks for a total of 9 sessions. All subjects will undergo Ocular Coherence Tomography (OCT), Fundus and Autofluorescence (FAF) prior to enrollment to ensure non-neovascular AMD. All subjects will be assessed with ETDRS Visual Acuity, Contrast Sensitivity, Radner Reading Test and Visual Function Questionnaire-25 (QoL). Clinical and imaging measurements will take place prior to treatment, immediately following the treatment and at specified follow-up visits. The grant will support a novel non-invasive, non-pharmaceutical, cost-effective therapy for Dry AMD.

Public Health Relevance Statement:
PROJECT NARRATIVE The current grant application addresses a novel, non-invasive photobiomodulation 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 United States alone. There are no approved treatments for dry AMD and, thus it represents a potential high impact, targeted area in medicine.

Project Terms:
Activities of Daily Living; Address; Adverse event; Affect; Age; age related; Age related macular degeneration; Anatomy; Angiography; Antiinflammatory Effect; Applications Grants; Area; Award; base; Blindness; Canada; Cell physiology; Cessation of life; Clinical; Clinical Data; Clinical Trials; Clinical Trials Design; Contrast Sensitivity; cost effective; Data; design; Developed Countries; Developing Countries; Device or Instrument Development; Devices; Disease; Disease Progression; Drusen; effective therapy; Enrollment; Ensure; Europe; follow-up; fovea centralis; Fundus; geographic atrophy; Grant; Healthcare Systems; Image; Industry; instrument; Intravenous; Light; Marketing; Masks; Measurement; Medical; Medical Device; Medicine; meetings; Metabolic; meter; Mitochondria; Multi-Institutional Clinical Trial; Multicenter Studies; novel; Ophthalmologist; Ophthalmology; Outcome; Outcome Measure; Patient Recruitments; Patients; Phase; photobiomodulation; Phototherapy; Pilot Projects; Placebos; Population; Prevalence; prevent; Preventive; Principal Investigator; programs; prospective; Publishing; Quality of life; Questionnaires; Randomized; Reading; Reporting; research clinical testing; Resources; Respiratory Chain; restorative treatment; Retinal; Risk; Route; Scanning; Series; Sister; Site; slow potential; Small Business Innovation Research Grant; Specialist; Specific qualifier value; Speed; System; Testing; Thick; tissue regeneration; tissue repair; Tissues; tomography; treatment group; Treatment Protocols; trial design; United States; United States Food and Drug Administration; United States National Institutes of Health; Vision; Visit; Visual Acuity; Visual impairment; Work