Recently, we found extensive remodeling of the microvasculature of the retina, occurring in some diabetic patients much earlier than expected. This provides the potential for novel biomarkers. However, the equipment is too expensive for most clinics and small practices. These early retinal microvascular changes cannot be seen with routine clinical examination or traditional imaging devices. We propose to reduce the cost and improve ease of use of this technology to allow widespread detection of retinal microvascular changes as biomarkers. Part of the high cost of these devices is the adaptive optics (AO) subsystem, which is deformable mirrors needed to provide compensation for the aberrations of the optics of the human eye. By planning for high resolution, but less than diffraction limited resolution, a wider field of view and less extreme deformable mirror performance can be realized. The important capillary changes will be nevertheless visualized in the retina. We propose 3 Aims.
In Aim 1, we will optimize a lower cost retinal imager, the Digital Light Ophthalmoscope (DLO), for high magnification and high contrast imaging that is sufficient to visualize retinal capillaries and cones outside the central fovea. Aeon will build a DLO with a mid- size for the field of view, which provides an image sufficiently large to show capillary networks in a single image, with the capillaries and cones being better visualized following image processing. This also more readily allows the montaging of AO images taken sequentially for this Phase I proposal.
In Aim 2, we will develop the AO subsystem for the AO-DLO to correct aberrations of the human eye, so that the high resolution images are high contrast. We will use a commercially available, visible wavelength deformable mirror and adapt the custom AO sensor and control techniques from existing, custom software. These Hartman Shack control algorithms and software are published and have been shared with other institutions. One key feature is the ability to use a smaller region of the pupil in older subjects.
In Aim 3, we wil develop an AO-DLO by integrating AO with the DLO, and map the microcirculation of the retina in 10 normal subjects. We will compare the capillary perfusion maps to corresponding maps from the AO Scanning Laser Ophthalmoscope (AO-SLO), that was used discover the retinal microvascular changes. For both AO-DLO and AO-SLO, we will produce capillary maps by collecting a series of images from the AO-DLO, aligning them, and plotting the variance of scaled images. This is possible because the moving blood particles lead to differing amounts of reflectivity over time, whereas the remaining retinal reflectivity is relatively unchanged in the wavelength range that we use. Then we will compare the test-retest of the capillary maps for each device vs. the comparison of the two devices.
Recently, we found extensive remodeling of the microvasculature of the retina, occurring in some patients much earlier than expected. These novel biomarkers are seen in diabetic retinas by using equipment that is too expensive for most clinics and small practices, but these early retinal microvascular changes cannot be seen with routine clinical examination or traditional imaging devices. We propose to reduce the cost and improve ease of use of this technology to allow widespread detection of microvascular changes as biomarkers.
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