Joel A. Papay

Cone Photoreceptor Packing Density and the Outer Nuclear Layer Thickness in Healthy Subjects

PURPOSE We evaluated the relationship between cone photoreceptor packing density and outer nuclear layer (ONL) thickness within the central 15 degrees. METHODS Individual differences for healthy subjects in cone packing density and ONL thickness were examined in 8 younger and 8 older subjects, mean age 27.2 versus 56.2 years. Cone packing density was obtained using an adaptive optics scanning laser ophthalmoscope (AOSLO). The ONL thickness measurements included the ONL and the Henle fiber layer (ONL + HFL), and were obtained using spectral domain optical coherence tomography (SDOCT) and custom segmentation software. RESULTS There were sizeable individual differences in cone packing density and ONL + HFL thickness. Older subjects had on average lower cone packing densities, but thicker ONL + HFL measurements. Cone packing density and ONL + HFL thickness decreased with increasing retinal eccentricity. The ratio of the cone packing density-to-ONL2 was larger for the younger subjects group, and decreased with retinal eccentricity. CONCLUSIONS The individual differences in cone packing density and ONL + HFL thickness are consistent with aging changes, indicating that normative aging data are necessary for fine comparisons in the early stages of disease or response to treatment. Our finding of ONL + HFL thickness increasing with aging is inconsistent with the hypothesis that ONL measurements with SDOCT depend only on the number of functioning cones, since in our older group cones were fewer, but thickness was greater.

Distribution differences of macular cones measured by AOSLO: Variation in slope from fovea to periphery more pronounced than differences in total cones

HIGHLIGHTSCone density varies among individuals by more than just a scalar factor.Cone density in the macular center is inversely proportional to the density at 7 deg.Total cones in the retinal can be modelled from the density along 4 meridians.Variation in cone density is greater nearer the fovea.Variation in total cones in the central 14 deg is less variable than for the fovea. ABSTRACT Large individual differences in cone densities occur even in healthy, young adults with low refractive error. We investigated whether cone density follows a simple model that some individuals have more cones, or whether individuals differ in both number and distribution of cones. We quantified cones in the eyes of 36 healthy young adults with low refractive error using a custom adaptive optics scanning laser ophthalmoscope. The average cone density in the temporal meridian was, for the mean ± SD, 43,216 ± 6039, 27,466 ± 3496, 14,996 ± 1563, and 12,207 ± 1278 cones/mm2 for 270, 630, 1480, and 2070 &mgr;m from the foveal center. Cone densities at 630 &mgr;m retinal eccentricity were uncorrelated to those at 2070 &mgr;m, ruling out models with a constant or proportional relation of cone density to eccentricity. Subjects with high central macula cone densities had low peripheral cone densities. The cone density ratio (2070:630 &mgr;m) was negatively correlated with cone density at 630 &mgr;m, consistent with variations in the proportion of peripheral cones migrating towards the center. We modelled the total cones within a central radius of 7 deg, using the temporal data and our published cone densities for temporal, nasal, superior, and inferior meridians. We computed an average of 221,000 cones. The coefficient of variation was 0.0767 for total cones, but higher for samples near the fovea. Individual differences occur both in total cones and other developmental factors related to cone distribution.

Sd-oct and Adaptive Optics Imaging of Outer Retinal Tubulation.

ABSTRACT Purpose To investigate outer retinal tubulation (ORT) using spectral domain optical coherence tomography (SD-OCT) and an adaptive optics scanning laser ophthalmoscope (AOSLO). To document the frequency of ORT in atrophic retinal conditions and quantify ORT dimensions versus adjacent retinal layers. Methods SD-OCT images were reviewed for the presence of retinal atrophy, scarring, and/or exudation. The greatest width of each ORT was quantified. Inner and outer retinal thicknesses adjacent to and within the area of ORT were measured for 18 patients. AOSLO imaged ORTs in five subjects with direct and scattered light imaging. Results ORT was identified in 47 of 76 subjects (61.8%) and in 65 eyes via SD-OCT in a wide range of conditions and ages, and in peripapillary atrophy. ORTs appeared as finger-like projections in atrophy, seen in the en face images. AOSLO showed some ORTs with bright cones that guide light within atrophic areas. Multiply scattered light mode AOSLO visualized variegated lines (18–35 μm) radiating from ORTs. The ORTs’ width on OCT b-scan images varied from 70 to 509 μm. The inner retina at the ORT was significantly thinner than the adjacent retina, 135 vs.170 μm (P = .004), whereas the outer retina was significantly thicker, 115 vs. 80 μm (P = .03). Conclusions ORTs are quite common in eyes with retinal atrophy in various disorders. ORTs demonstrate surviving photoreceptors in tubular structures found within otherwise nonsupportive atrophic areas that lack retinal pigment epithelium and choriocapillaris.

Fixation Stability and Scotoma Mapping for Patients with Low Vision

Purpose To develop a simplified device that performs fundus perimetry techniques such as fixation mapping and kinetic perimetry. Methods We added visual stimulation to a near-infrared retinal imager, the laser scanning digital camera (LSDC). This device uses slit scanning illumination combined with a two-dimensional CMOS (complementary metal oxide semiconductor) detector, with continuous viewing of the retina. The CMOS readout was synchronized with the slit scanning, thereby serving as a confocal aperture to reduce stray light in retinal images. A series of retinal images of 36 degrees was automatically aligned to provide data for fixation maps and quantification of fixation stability. The LSDC and alignment techniques also provided fundus viewing with retinal location correction for scotoma mapping. Results First, fixation mapping was readily performed in patients with central scotoma or amblyopia. The automatic alignment algorithm allowed quantification of fixation stability in patients with macular pathologies that did not cause scotoma. Second, fixation stability was rapidly and quantitatively assessed by the automatic registration of the series of retina images. There was no significant difference in the fixation stability with automatic versus manual alignment. Kinetic perimetry demonstrated that fundus imaging helped reduce the variability of perimetric data by identifying and preventing false-positives caused by eye motion. We found that the size of the blind spot was significantly larger for dark targets on brighter backgrounds than when the contrast was reversed (p < 0.045). This is consistent with incremental targets being detected partially or wholly because of scattered light falling on more sensitive retinal locations. Conclusions Fundus perimetry with the LSDC allows for a wide range of fixation and perimetry tasks.

Subtle changes in diabetic retinas localised in 3D using OCT

To detect and localise subtle changes in retinas of diabetic patients who clinically have no diabetic retinopathy (DR) or non‐proliferative DR (NPDR) as compared to age‐ and sex‐ matched controls. Spectral Domain Optical Coherence Tomography (SD‐OCT) and software to examine all retinal layers, including deeper layers, were used to quantify foveal avascular zone size and inner and outer retinal layer thicknesses, as well as to detect axial location of prominent lesions.

Axial analysis of cones and adjacent retinal structures using AOSLO(Conference Presentation)

We imaged the retina using the Indiana Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO). Our system uses two deformable mirrors to provide en face, high-resolution images of retinal structures at a 28 Hz frame rate. The wavelength of the sensor light was 850 nm and the imaging wavelength was 820 nm at 50 and 120 W respectively. The confocal pinhole was located in a position conjugate with the retina allowed us to segment one retina plane. Two different confocal apertures of 75 m and 100 m (1.5 and 2 times the Airy disk size) were used to provide different amounts of confocal or scattered light. The imaging area was 1.4 x 1.2 deg which corresponds roughly to 400 x 350 m. Using the large stroke deformable mirror, which provides the focusing capability of the confocal system, we imaged the same location at different planes. We moved from superficial layers to the retinal pigment epithelium in 0.3 D increments. The range of adjustments included the subjectively best overall image, and focal planes anterior and posterior to this. We imaged 10 subjects at approximately 7.5 deg temporal from the fovea. A video of individual frames was taken, and the individual frames were dewarped, aligned, and averaged. We measured 10 bright and 10 dim cones for each subject at the 10 depths, with brightness groupings based subjectively on the most superficial location. The function for amount of light reflected differed for the two groups of cones. Reflectivity varied as a function of depth.

Polarimetric Imaging of the Human Retina for the Quantification of Neural and Blood Vessel Status

A Several key structures and molecules in the human retina are known to exhibit birefringence, and therefore can be probed with polarimetric imaging. By using scanned illumination, the contrast is increased, revealing otherwise undetectable pathology.

Toward Low Cost Imaging: A Laser Scanning Digital Camera

The laser scanning digital camera is a hybrid confocal imager, designed with simplified optics and electronics to reduce the costs of diagnostic imaging, presentation of visual stimuli, and measurement of refractive error.

Probing Global Aging Changes to Photoreceptors

Global changes with age in the density of photoreceptors were investigated by using novel software to compute the thickness of the outer nuclear layer seen with Optical Coherence Tomography.

Fundus Scattered Light in the Near Infrared and Changes with Aging not Associated with the Anterior Segment

A confocal scanning laser polarimetry technique using near infrared light reveals an increase with aging in scattered light returning from the ocular fundus. The increase is not associated with dry eye or cataract.