SBIR-STTR Award

Age-related macular degeneration remains the most common cause of permanent vision loss in the US and many industrialized countries. Extensive attention is paid to developing treatments, resulting in 680 registered treatment trials in the US. The large numbers of patients and trials accentuates the need for improved biomarkers for the management of patients. Further, if outcome measures, including visual acuity, could be made more accurate and have decreased test-retest variability, then clinical trials could use smaller sample sizes. This leads to a savings in cost and time to bring therapies to market. We will minimize the issues from the optics of the aging eye by building a Maxwellian view device with a low cost but high resolution display suitable for visual acuity testing. Simultaneous retinal imaging and onboard focus will decrease the artifact from target defocus from retinal elevation due to exudative age-related macular degeneration. The part of the retina that is used for visual acuity will be localized. Related devices for microperimetry are more expensive and lack the resolution needed for visual acuity. We will use psychophysical techniques that are rapid, accurate, and provide better measures of variability: 2 alternative forced choice with Method of Constant Stimuli and ZEST. In Aim 1, we will build a version of the digital light ophthalmoscope (DLO) that has a high resolution visual display and NIR illumination for retinal imaging. The imaging light is comfortable and dim enough not to interfere with visual tasks. The DLO projects a series of stripes onto the retina in a raster pattern, providing line scanning for imaging, therefore increasing contrast even in the aging eye and exudation. The detection is via a 2D CMOS detector with a rolling shutter, with the serial read-out of the lines either synchronized with the illumination or offset in time. This provides a flexible electronic aperture under computer control. Both confocal and multiply scattered light images are available during visual function testing, revealing drusen and other subretinal deposits, or locations of sub-retinal treatment. We will optimize image quality and autofocus ability in 10 subjects with a range of refractive error, ocular pigmentation, and age. In Aim 2, we will optimize our novel method of visual acuity measurement. To model performance in aging eyes or those with macular degeneration, we will measure at 20/20 and also degrade vision in 40 subjects with Bangerter foils to 20/40, 20/60 and 20/80 and compare to ETDRS charts, then test with spatial pattern noise that masks the letters. In Aim 3, we will develop new software that is robust in aging eyes to support a variety of visual function tests, capable of focusing and registering visual targets to a specific location on the retina. We will test 20 normal subjects, and 10 patients with age-related macular degeneration. This project can move high quality visual testing into clinical trials, research facilities, and eventually the lane.

Public Health Relevance Statement:
Project Narrative Age-related macular degeneration is the most common cause of vision loss in the US. Both the management of an individual patient and the cost and speed of clinical trials for new treatments can be improved by more accurate outcome measures, including the commonplace visual acuity. We propose to improve the measurement of visual function by reducing the influence of artifacts due to aging eyes and poor focus and localization of visual targets for eyes with exudative age-related macular degeneration.

Project Terms:
Address; Adult; Age; age effect; Age related macular degeneration; Aging; Anterior; Atrophic; Attention; bevacizumab; Biological Markers; Blindness; Cataract; Cellular Phone; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Trials; Computer software; Computers; Contrast Sensitivity; cost; cost effective; Custom; Deposition; design; Detection; detector; Developed Countries; Devices; digital; Drusen; Electronics; Ethnic group; Exudative age-related macular degeneration; Eye; Female; Film; flexibility; Fundus; fundus imaging; Goals; Hyperopia; Hyperpigmentation; Image; improved; improved outcome; Individual; individual patient; Injections; Intervention; Intervention Trial; Lasers; Lead; lens; Lesion; Letters; Light; light effects; light intensity; light scattering; Lighting; Liquid substance; Location; Macular degeneration; male; Masks; Measurement; Measures; Methods; Miosis disorder; Modeling; Morphologic artifacts; Noise; novel; older patient; Ophthalmoscopes; Optics; Outcome Measure; overtreatment; Pathway interactions; Patients; Pattern; Performance; Phase; Photoreceptors; Pigmentation physiologic function; Population; Psychophysics; Pupil; rapid technique; Refractive Errors; Reproducibility; research facility; Resolution; Retina; Retinal; Retinal Degeneration; Retinal Diseases; retinal imaging; Sample Size; Savings; Scanning; screening; Series; Small Business Innovation Research Grant; software development; Source; Speed; Stimulus; Structure of retinal pigment epithelium; Surface; Testing; therapy development; Time; Treatment Cost; treatment trial; Uncertainty; Vision; Visual; Visual Acuity; Visual impairment; visual stimulus

Age-related macular degeneration (AMD) remains the most common cause of permanent vision loss in the USand many industrialized countries. Diabetic retinopathy and diabetic macular edema are the leading cause ofvisual acuity loss in working age Americans. Visual function is a key component in almost all of the 1,861 USclinical trials for AMD and 262 for diabetic retinopathy and macular edema. If outcome measures, includingvisual acuity, could be made more accurate and cost-effective and with decreased test-retest variability, thenclinical trials could use smaller sample sizes, giving savings in cost and time to bring therapies to market. Bybuilding a new device, the Potential Vision Tester™ (PVT), we will improve measurements by minimizing theissues from the optics of the aging eye. Simultaneous retinal imaging will clarify fixation locus and fixationstability of the patient's eye. The optical errors of a patient's eye will be measured as wavefront aberrations,and the target display will be corrected with moderately priced adaptive optics to overcome retinal elevationfrom exudation as well as refractive error. Reporting out of wavefront errors distinguishes between neuraldamage vs. optical issues. A high resolution display, suitable for visual acuity testing, will project stimuli ontothe eye in Maxwellian view to minimize pupil size effects found in older eyes. Competing devices formicroperimetry lack the resolution needed for visual acuity. We will use psychophysical techniques that arerapid, accurate, and provide better measures of variability: 4 alternative forced choice. In Aim 1, we will buildan adaptive optics-corrected PVT visual display and NIR illumination for retinal imaging. The imaging light iscomfortable and dim enough not to interfere with visual tasks. The patented NIR imaging technology projectsa series of stripes onto the retina in a raster pattern, providing line scanning for imaging. The detection is via a2D CMOS detector with a rolling shutter, with the serial read-out of the lines either synchronized with theillumination or offset in time. This provides a flexible electronic aperture under computer control. Bothconfocal and multiply scattered light images are available, revealing drusen and other subretinal thickening.We will optimize image quality in 10 subjects with a range of refractive error, ocular pigmentation, and age. InAim 2, we will quantify and validate the Hartmann-Shack wavefront measurements of the PVT in 20 patientswith retinal disease vs. 20 without to determine the effect on wavefront measurements. In Aim 3 we willoptimize the algorithm for efficient testing and metric for Potential Visual Acuity (PVA), using data from Aims 1and 2, reporting central tendency (expected value) and variability, including optical errors and fixation data, toaddress the acuity this patient could reach with retinal treatment. In Aim 4, for 20 patients with exudative AMDand 20 with diabetic macular edema, we will assess PVA reproducibility and validity by comparison to standardVA and the prediction at baseline to actual post-treatment measured VA and PVA at follow up.

Public Health Relevance Statement:
Project Narrative Age-related macular degeneration is the most common cause of vision loss in the US, and diabetic retinopathy and diabetic macular edema for working age adults. Both the management of an individual patient and the cost and speed of clinical trials for new treatments need more accurate outcome measures, including visual acuity. We propose to improve the measurement of visual function by quantifying and reducing the influence of artifacts, crucial in aging eyes that have inherent optical artifacts and small pupils, using localization of visual targets for eyes with exudative age-related macular degeneration.

Project Terms:
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