Ann E. Elsner

Infrared imaging of sub-retinal structures in the human ocular fundus

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 Bruchs membrane, such as age-related macular degeneration.

Deep Retinal Vascular Anomalous Complexes in Advanced Age-related Macular Degeneration

PURPOSE The authors describe the clinical characteristics of a group of patients with age-related macular degeneration (AMD), deep retinal vascular anomalous complexes (RVACs), advanced Bruch membrane changes, and severe visual loss. Based on clinical evaluation and imaging studies, the authors hypothesize the cause of such retinal vascular formations. PATIENTS AND METHODS The authors quantified an initial case series of 6 patients and expanded it to 11 patients (14 eyes) with AMD and RVACs diagnosed by fluorescein angiography or slit-lamp examination. Associated pigment epithelial detachments (PEDs) of 13 eyes are described. In addition to the clinical and fluorescein angiography descriptions, infrared imaging and indocyanine green angiography were used to characterize more recently described RVACs and fellow eyes. RESULTS Each study eye had a clearly defined anastomosis connecting the retinal circulation to a vascular complex in the deep retina. The RVACs associated with PEDs assumed a more central location than did typical choroidal neovascularization associated with PEDs. In seven eyes with RVACs, there were clinically recognizable retinovascular findings: intraretinal hemorrhages, telangiectasia, or microaneurysms. Legal blindness occurred in 9 of 11 patients. CONCLUSION These results indicate that retinovascular changes can be associated with nondisciform AMD. The authors speculate that neurodegenerative changes and hypoxia may lead to such changes, the RVAC being a more advanced finding. Closure of an RVAC with photocoagulation is difficult, perhaps because of its higher blood flow. The visual outcome is poor, not only because of the advanced state of the underlying AMD, but also because of the exudative nature of the RVAC.

Large Field of View, Modular, Stabilized, Adaptive-Optics-Based Scanning Laser Ophthalmoscope

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 ophthalmoscope (SLO), and a high-resolution microelectromechanical-systems-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 psf. The retinal image was stabilized to within 18 microm 90% of the time. Stabilization was sufficient for cross-correlation techniques to automatically align the images.

The abney effect: Chromaticity coordinates of unique and other constant hues

We compared unique and other constant hue loci measured at a fixed retinal illuminance for the same observers. When expressed in Judd chromaticity coordinates, unique hue and constant hue data agreed. Unique blue loci were curved, and unique red and green loci were noncollinear. These data imply that unique hues are not a linear transformation of color matching functions. Linear models are only an approximation, even at a single luminance level.

Image stabilization for scanning laser ophthalmoscopy

A scanning laser ophthalmoscope with an integrated retinal tracker (TSLO) was designed, constructed, and tested in human subjects without mydriasis. The TSLO collected infrared images at a wavelength of780 nm while compensating for all transverse eye movements. An active, high-speed, hardware-based tracker was able to lock onto many common features in the fundus, including the optic nerve head, blood vessel junctions, hypopigmentation, and the foveal pit. The TSLO has a system bandwidth of ~1 kHz and robustly tracked rapid and large saccades of approximately 500 deg/sec with an accuracy of 0.05 deg. Image stabilization with retinal tracking greatly improves the clinical potential of the scanning laser ophthalmoscope for imaging where fixation is difficult or impossible and for diagnostic applications that require long duration exposures to collect meaningful information.

Variation of cone photoreceptor packing density with retinal eccentricity and age.

PURPOSE To study the variation of cone photoreceptor packing density across the retina in healthy subjects of different ages. METHODS High-resolution adaptive optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically image the retinas of two groups of subjects of different ages. Ten younger subjects (age range, 22-35 years) and 10 older subjects (age range, 50-65 years) were tested. Strips of cone photoreceptors, approximately 12° × 1.8° long were imaged for each of the four primary retinal meridians: superior, inferior, nasal, and temporal. Cone photoreceptors within the strips were counted, and cone photoreceptor packing density was calculated. Statistical analysis (three-way ANOVA) was used to calculate the interaction for cone photoreceptor packing density between age, meridian, and eccentricity. RESULTS As expected, cone photoreceptor packing density was higher close to the fovea and decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (∼0.6-12°). Older subjects had approximately 75% of the cone density at 0.18 mm (∼0.6°), and this difference decreased rapidly with eccentricity, with the two groups having similar cone photoreceptor packing densities beyond 0.5 mm retinal eccentricity on average. CONCLUSIONS 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.

Direct measurement of human-cone- photoreceptor alignment

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 eyes 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.

Reflectometry with a scanning laser ophthalmoscope.

We describe noninvasive techniques to optimize reflectometry measurements, particularly retinal densitometry, which measures the photopigment density difference. With these techniques unwanted scattered light is greatly reduced, and the retina is visualized during measurements. Thus results may be compared for each retinal location, and visible artifacts are minimized. The density difference measurements of the cone photopigment depend on the optical configuration of the apparatus. The cone photopigment density difference is greatest near the fovea and for most observers decreases rapidly with eccentricity. A research version for reflectometry and psychophysics of the scanning laser ophthalmoscope is described.

Imaging Polarimetry in Age-Related Macular Degeneration

PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques--scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)--and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD.

Analysis of Nonlinearities in the Flicker ERG

The electroretinogram (ERG) response to steadily flickering fields shows significant nonlinear components. These nonlinear components have been used to investigate the ERG. We find the following. (1) The fundamental retinal response can be recorded at frequencies greater than 100 Hz and the second and higher harmonic responses have measurable response frequencies as high as 200 Hz. Both the fundamental response component and the second harmonic response component have multiple local maxima as a function of frequency. (2) Measurement of the response of the retina to the sum of two sine waves indicates that there is an early low-pass temporal filter in the retina. This early filter has a cutoff frequency between 40 and 50 Hz. (3) The high frequency nonlinearity is not a compressive nonlinearity.