Project Grant R44EY030829

VISUAL ACUITY AND FUNCTIONAL MEASUREMENTS IN THE AGING EYE - PROJECT SUMMARY AGE-RELATED MACULAR DEGENERATION (AMD) REMAINS THE MOST COMMON CAUSE OF PERMANENT VISION LOSS IN THE US AND MANY INDUSTRIALIZED COUNTRIES. DIABETIC RETINOPATHY AND DIABETIC MACULAR EDEMA ARE THE LEADING CAUSE OF VISUAL ACUITY LOSS IN WORKING AGE AMERICANS. VISUAL FUNCTION IS A KEY COMPONENT IN ALMOST ALL OF THE 1,861 US CLINICAL TRIALS FOR AMD AND 262 FOR DIABETIC RETINOPATHY AND MACULAR EDEMA. IF OUTCOME MEASURES, INCLUDING VISUAL ACUITY, COULD BE MADE MORE ACCURATE AND COST-EFFECTIVE AND WITH DECREASED TEST-RETEST VARIABILITY, THEN CLINICAL TRIALS COULD USE SMALLER SAMPLE SIZES, GIVING SAVINGS IN COST AND TIME TO BRING THERAPIES TO MARKET. BY BUILDING A NEW DEVICE, THE POTENTIAL VISION TESTER (PVT), WE WILL IMPROVE MEASUREMENTS BY MINIMIZING THE ISSUES FROM THE OPTICS OF THE AGING EYE. SIMULTANEOUS RETINAL IMAGING WILL CLARIFY FIXATION LOCUS AND FIXATION STABILITY 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 ELEVATION FROM EXUDATION AS WELL AS REFRACTIVE ERROR. REPORTING OUT OF WAVEFRONT ERRORS DISTINGUISHES BETWEEN NEURAL DAMAGE VS. OPTICAL ISSUES. A HIGH RESOLUTION DISPLAY, SUITABLE FOR VISUAL ACUITY TESTING, WILL PROJECT STIMULI ONTO THE EYE IN MAXWELLIAN VIEW TO MINIMIZE PUPIL SIZE EFFECTS FOUND IN OLDER EYES. COMPETING DEVICES FOR MICROPERIMETRY LACK THE RESOLUTION NEEDED FOR VISUAL ACUITY. WE WILL USE PSYCHOPHYSICAL TECHNIQUES THAT ARE RAPID, ACCURATE, AND PROVIDE BETTER MEASURES OF VARIABILITY: 4 ALTERNATIVE FORCED CHOICE. IN AIM 1, WE WILL BUILD AN ADAPTIVE OPTICS-CORRECTED PVT VISUAL DISPLAY AND NIR ILLUMINATION FOR RETINAL IMAGING. THE IMAGING LIGHT IS COMFORTABLE AND DIM ENOUGH NOT TO INTERFERE WITH VISUAL TASKS. THE PATENTED NIR IMAGING TECHNOLOGY PROJECTS A SERIES OF STRIPES ONTO THE RETINA IN A RASTER PATTERN, PROVIDING LINE SCANNING FOR IMAGING. 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, REVEALING DRUSEN AND OTHER SUBRETINAL THICKENING. WE WILL OPTIMIZE IMAGE QUALITY IN 10 SUBJECTS WITH A RANGE OF REFRACTIVE ERROR, OCULAR PIGMENTATION, AND AGE. IN AIM 2, WE WILL QUANTIFY AND VALIDATE THE HARTMANN-SHACK WAVEFRONT MEASUREMENTS OF THE PVT IN 20 PATIENTS WITH RETINAL DISEASE VS. 20 WITHOUT TO DETERMINE THE EFFECT ON WAVEFRONT MEASUREMENTS. IN AIM 3 WE WILL OPTIMIZE THE ALGORITHM FOR EFFICIENT TESTING AND METRIC FOR POTENTIAL VISUAL ACUITY (PVA), USING DATA FROM AIMS 1 AND 2, REPORTING CENTRAL TENDENCY (EXPECTED VALUE) AND VARIABILITY, INCLUDING OPTICAL ERRORS AND FIXATION DATA, TO ADDRESS THE ACUITY THIS PATIENT COULD REACH WITH RETINAL TREATMENT. IN AIM 4, FOR 20 PATIENTS WITH EXUDATIVE AMD AND 20 WITH DIABETIC MACULAR EDEMA, WE WILL ASSESS PVA REPRODUCIBILITY AND VALIDITY BY COMPARISON TO STANDARD VA AND THE PREDICTION AT BASELINE TO ACTUAL POST-TREATMENT MEASURED VA AND PVA AT FOLLOW UP.