Cone packing density in the living human retina decreases as a function of age within the foveal center with the largest difference being found at our most central measurement site. At all ages, the retina showed meridional difference in cone densities, with cone photoreceptor packing density decreasing faster with increasing eccentricity in the vertical dimensions than in the horizontal dimensions.

The interaction of infrared light with the human ocular fundus, particularly sub-retinal structures, was studied in vivo. Visible and infra-red wavelengths and a scanning laser ophthalmoscope were used to acquire digital images of the human fundus. The contrast and reflectance of selected retinal and sub-retinal features were computed for a series of wavelengths or modes of imaging. Near infrared light provides better visibility than visible light for sub-retinal features. Sub-retinal deposits appear light and thickened; the optic nerve head, retinal vessels, and choroidal vessels appear dark. Contrast and visibility of features increases with increasing wavelength from 795 to 895 nm. Optimizing the mode of imaging improves the visibility of some structures. This new quantitative basis for near infrared imaging techniques can be applied to a wide range of imaging modalities for the study of pathophysiology and treatment in diseases affecting the retinal pigment epithelium and Bruch's membrane, such as age-related macular degeneration.

We describe the design and performance of an adaptive optics retinal imager that is optimized for use during dynamic correction for eye movements. The system incorporates a retinal tracker and stabilizer, a wide field line scan Scanning Laser Ophthalmocsope (SLO), and a high resolution MEMS based adaptive optics SLO. The detection system incorporates selection and positioning of confocal apertures, allowing measurement of images arising from different portions of the double pass retinal point spread function (psf). System performance was excellent. The adaptive optics increased the brightness and contrast for small confocal apertures by more than 2x, and decreased the brightness of images obtained with displaced apertures, confirming the ability of the adaptive optics system to improve the pointspread function. The retinal image was stabilized to within 18 microns 90% of the time. Stabilization was sufficient for cross-correlation techniques to automatically align the images.

Abstract:We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with nonproliferative diabetic retinopathy (NPDR). To improve visualization of different retinal features, the size and alignment of the confocal aperture were varied. The inner retinal layers contained clearly visualized retinal vessels. In diabetic subjects there was extensive capillary remodeling despite the subjects having only mild or moderate NPDR. Details of the retinal microvasculature were readily imaged with a larger confocal aperture. Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor layer images showed regions of bright cones and dark areas, corresponding in location to overlying vascular abnormalities and retinal edema. Clinically undetected intraretinal vessel remodeling and varying blood flow patterns were found. Perifoveal capillary diameters were larger in the diabetic subjects (p<0.01), and small arteriolar walls were thickened, based on wall to lumen measurements (p<.05). The results suggest that existing clinical classifications based on lower magnification clinical assessment may not adequately measure key vascular differences among individuals with NPDR.

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Adaptive Optics (AO) retinal imaging has provided revolutionary tools to scientists and clinicians for studying retinal structure and function in the living eye. From animal models to clinical patients, AO imaging is changing the way scientists are approaching the study of the retina. By providing cellular and subcellular details without the need for histology, it is now possible to perform large scale studies as well as to understand how an individual retina changes over time. Because AO retinal imaging is non-invasive and when performed with near-IR wavelengths both safe and easily tolerated by patients, it holds promise for being incorporated into clinical trials providing cell specific approaches to monitoring diseases and therapeutic interventions. AO is being used to enhance the ability of OCT, fluorescence imaging, and reflectance imaging. By incorporating imaging that is sensitive to differences in the scattering properties of retinal tissue, it is especially sensitive to disease, which can drastically impact retinal tissue properties. This review examines human AO retinal imaging with a concentration on the use of the Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO). It first covers the background and the overall approaches to human AO retinal imaging, and the technology involved, and then concentrates on using AO retinal imaging to study the structure and function of the retina.

We have developed an imaging reflectometer to measure cone-photoreceptor alignment. One makes measurements by bleaching the cone photopigment and imaging the distribution of light returning from the retina, which is illuminated from a small source imaged in the plane of the eye's pupil. If the source is near the optimal entry pupil position as determined psychophysically, the distribution of light returning from the retina is peaked, and the magnitude of the peak depends on the location of the source in the pupil of the eye. If the source is far from the optimal entry pupil position, then there is no measurable peak. The location of the peak varies across individuals and coincides with the reported location of best visibility of the measuring light and with previous psychophysical and reflectometric measurements of the Stiles-Crawford peak. The source of this directionality must arise either from the photoreceptors or from behind the photoreceptors because the peak is not present if measurements are made when the cone photopigments have high optical density.

Despite large individual variations in size and shape of the FAZ, the INLFAZ has a relatively constant thickness at the margins of the FAZ, suggesting the presence of retinal capillaries is needed to sustain an INLFAZ thickness greater than 60 μm. A smaller FAZ area is associated with a vertically elongated FAZ.