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Purpose: To develop a sensitive psychophysical test for detecting visual defects such as microscotomas., Methods: Frequency-of-seeing curves were measured with 0.75' and 7.5' spots. On each trial, from 0 to 4 stimuli were randomly presented at any of eight equally spaced loci 0.5 degrees from fixation. By correcting the aberrations of the eye, adaptive optics produced retinal images of the 0.75' spot that were 3.0 microm wide at half height, small enough to be almost entirely confined within the typical cone diameter at this eccentricity. Data were collected from a patient with deuteranopia (AOS1) whose retina, imaged with adaptive optics, suggested that approximately 30% of his cones were missing or abnormal. Patients with protanomalous trichromacy (1 subject), deuteranopia (1 subject), and trichromacy (5 subjects) served as controls (all had normal cone density and complete cone mosaics). Psychophysical results were modeled by a Monte Carlo simulation incorporating measured properties of the cone mosaic., Results: Frequency-of-seeing curves for AOS1 obtained with 0.75' spots showed lower asymptote, slope, and sensitivity than for controls. The 7.5' results showed that these differences were the result of the small spot size, which on some trials was confined mostly to the locus of the putatively missing cones. A two-parameter model satisfactorily described the data and was highly sensitive to the proportion of missing cones simulated., Conclusions: Adaptive-optics microperimetry is a powerful psychophysical test for assessing the loss of neural elements, even in retinas that appear otherwise normal in standard clinical tests. This technique may prove useful in estimating the proportion of missing cones in different patients and in detecting other visual losses such as those associated with glaucoma.

The ability to resolve single cells noninvasively in the living retina has important applications for the study of normal retina, diseased retina, and the efficacy of therapies for retinal disease. We describe a new instrument for high-resolution, in vivo imaging of the mammalian retina that combines the benefits of confocal detection, adaptive optics, multispectral, and fluorescence imaging. The instrument is capable of imaging single ganglion cells and their axons through retrograde transport in ganglion cells of fluorescent dyes injected into the monkey lateral geniculate nucleus (LGN). In addition, we demonstrate a method involving simultaneous imaging in two spectral bands that allows the integration of very weak signals across many frames despite inter-frame movement of the eye. With this method, we are also able to resolve the smallest retinal capillaries in fluorescein angiography and the mosaic of retinal pigment epithelium (RPE) cells with lipofuscin autofluorescence.

Purpose: This study examines a patient with cone-rod dystrophy using high-resolution adaptive optics retinal imaging. Conventional ophthalmoscopes provide limited resolution due to their inability to overcome the eye's optical aberrations. In contrast, adaptive optics ophthalmoscopes correct these aberrations to provide noninvasive high-resolution views of the living retina. To date, adaptive optics ophthalmoscopy has been used mainly to examine the normal retina. Here we use adaptive optics ophthalmoscopy to image cone-rod dystrophy in vivo and compare these results with standard clinical tests., Design: Observational case report., Methods: High-resolution retinal images of a patient with cone-rod dystrophy were obtained with the University of Rochester adaptive optics flood-illuminated ophthalmoscope and the adaptive optics scanning laser ophthalmoscope located at the University of Houston and compared with standard clinical tests, including fundus photography, Goldmann visual fields, fluorescein angiography, optical coherence tomography, electroretinography, and multifocal electroretinography., Main Outcome Measures: Direct measurement of cone density and diameter and comparison of adaptive optics images with standard clinical imaging and functional tests., Results: Adaptive optics images were acquired at multiple retinal locations throughout a clinically detected bull's-eye lesion. Within the atrophic regions, we observed large areas devoid of wave-guiding cones. In contrast, regions that appeared relatively spared by clinical examination contained a completely tiled cone mosaic. However, in these areas the cones were abnormally large, resulting in a 6.6-fold reduction from the normal peak cone density (patient peak density: 30 100 cones/mm2, normal peak density: 199 200 cones/mm2). Multifocal electroretinography confirmed a 5.5-fold reduction in amplitude of the central peak (10.8 nanovolts/degree2 vs. 59.8 nanovolts/degree2)., Conclusions: Adaptive optics ophthalmoscopy is a noninvasive technique to observe a patient's retinal pathology directly at a cellular level. It can provide a quantitative measurement of photoreceptor loss in retinal disease.