Project Summary/Abstract: It is known that individuals with Down syndrome (DS) have reduced visual acuity which may result from high levels of refractive error (sphere and cylinder) and elevated levels of higher-order aberrations that are present from childhood. Targeting optical aberrations through spectacle correction with refractions determined objectively from measures of wavefront aberrations is part of our long-term goal to provide new treatment strategies to improve vision in this group. The central hypothesis is that measures of visual and retinal image quality (metrics) can be used to identify sphere and cylinder corrections that optimize vision, resulting in multi-line acuity gains over traditional corrections. Our previous evaluation of these corrections in adults with DS found improvement in acuity, but not the multi-line levels predicted. We propose that this mismatch in acuity gains is attributed to decades of exposure to poorly corrected optical deficits that has resulted in a reduction in visual acuity potential (i.e. refractive amblyopia). Further, the method is inherently monocular, and does not prescribe refractions reflective of the two-eyed visual experience of the patient, as would occur in a clinical exam. The short-term goal of this work is to address these proposed barriers to multi- line acuity improvements with metric-optimized refractions through a randomized treatment trial conducted in children with DS who are within the optimal age for treatment of amblyopia. This trial will compare acuity outcomes for three refractive methods: 1) metric-optimized refractions, 2) clinical refractions, and 3) a hybrid method that allows for clinical refinement of the metric-optimized refraction. In addition, we seek to improve the objective refraction process by removing dilation prior to the wavefront imaging necessary to compute the metric values, as well as determining the rate of change in refraction during extended follow-up to guide patient recall times (i.e. follow-up intervals) for updated refraction. This work will be accomplished through three specific aims: Aim 1) Compare refractions and resultant visual acuity obtained from wavefront measures pre- and post-dilation. Aim 2) Compare visual acuity outcomes of metric-optimized, clinical, and clinically-refined metric-optimized refractions in a treatment trial of children with DS. Aim 3) Determine rate of change in refraction as a function of age and refractive error type annually over four years in children and adults with DS. Metric-optimized refraction is innovative in that it compensates for the absence of subjective input in the refraction process for the DS population and allows the clinician to consider corrections targeting overall image quality. This proposed research is significant in that it proposes to use spectacles in an optimized manner to remove visual barriers. Treatment of refractive amblyopia with multi-line acuity gains would lead to lifelong benefits, incl...