Evaluating Descriptive Metrics of the Human Cone Mosaic

Purpose: To evaluate how metrics used to describe the cone mosaic change in response to simulated photoreceptor undersampling (i.e., cell loss or misidentification). Methods: Using an adaptive optics ophthalmoscope, we acquired images of the cone mosaic from the center of fixation to 10° along the temporal, superior, inferior, and nasal meridians in 20 healthy subjects. Regions of interest (n = 1780) were extracted at regular intervals along each meridian. Cone mosaic geometry was assessed using a variety of metrics − density, density recovery profile distance (DRPD), nearest neighbor distance (NND), intercell distance (ICD), farthest neighbor distance (FND), percentage of six-sided Voronoi cells, nearest neighbor regularity (NNR), number of neighbors regularity (NoNR), and Voronoi cell area regularity (VCAR). The “performance” of each metric was evaluated by determining the level of simulated loss necessary to obtain 80% statistical power. Results: Of the metrics assessed, NND and DRPD were the least sensitive to undersampling, classifying mosaics that lost 50% of their coordinates as indistinguishable from normal. The NoNR was the most sensitive, detecting a significant deviation from normal with only a 10% cell loss. Conclusions: The robustness of cone spacing metrics makes them unsuitable for reliably detecting small deviations from normal or for tracking small changes in the mosaic over time. In contrast, regularity metrics are more sensitive to diffuse loss and, therefore, better suited for detecting such changes, provided the fraction of misidentified cells is minimal. Combining metrics with a variety of sensitivities may provide a more complete picture of the integrity of the photoreceptor mosaic

Evaluating Outer Segment Length as A Surrogate Measure of Peak Foveal Cone Density

Adaptive optics (AO) imaging tools enable direct visualization of the cone photoreceptor mosaic, which facilitates quantitative measurements such as cone density. However, in many individuals, low image quality or excessive eye movements precludes making such measures. As foveal cone specialization is associated with both increased density and outer segment (OS) elongation, we sought to examine whether OS length could be used as a surrogate measure of foveal cone density. The retinas of 43 subjects (23 normal and 20 albinism; aged 6–67 years) were examined. Peak foveal cone density was measured using confocal adaptive optics scanning light ophthalmoscopy (AOSLO), and OS length was measured using optical coherence tomography (OCT) and longitudinal reflectivity profile-based approach. Peak cone density ranged from 29,200 to 214,000 cones/mm2(111,700 ± 46,300 cones/mm2); OS length ranged from 26.3 to 54.5 μm (40.5 ± 7.7 μm). Density was significantly correlated with OS length in albinism (p \u3c 0.0001), but not normals (p = 0.99). A cubic model of density as a function of OS length was created based on histology and optimized to fit the albinism data. The model includes triangular cone packing, a cylindrical OS with a fixed volume of 136.6 μm3, and a ratio of OS to inner segment width that increased linearly with increasing OS length (R2 = 0.72). Normal subjects showed no apparent relationship between cone density and OS length. In the absence of adequate AOSLO imagery, OS length may be used to estimate cone density in patients with albinism. Whether this relationship exists in other patient populations with foveal hypoplasia (e.g., premature birth, aniridia, isolated foveal hypoplasia) remains to be seen

Assessing the Spatial Relationship Between Fixation and Foveal Specializations

Increased cone photoreceptor density, an avascular zone (FAZ), and the displacement of inner retinal neurons to form a pit are distinct features of the human fovea. As the fovea provides the majority of our vision, appreciating how these anatomical specializations are related is important for understanding foveal development, normal visual function, and retinal disease. Here we evaluated the relationship between these specializations and their location relative to the preferred retinal locus of fixation (PRL). We measured foveal pit volume, FAZ area, peak cone density, and location of the PRL in 22 subjects with normal vision using optical coherence tomography and adaptive optics scanning light ophthalmoscopy. Foveal pit volume was positively correlated with FAZ area; however, peak cone density was not correlated with pit volume. In addition, there was no systematic offset of the location of any of these specializations relative to PRL, and there was no correlation between the magnitude of the offset from PRL and the corresponding foveal specialization measurements (pit volume, FAZ area, peak cone density). The standard deviation of our PRL measurements was consistent with previous measurements of fixational stability. These data provide insight into the sequence of events during foveal development and may have implications for visual function and retinal disease

Strategies for Enhancing Diverse Mentoring Relationships in STEM Fields

Developing effective opposite-race mentorships in the STEM fields may contribute to minority student retention. Paying attention to the dynamics of race within the protégé’s professional and psychosocial growth may positively influence academic advancement and professional longevity. The current paper will provide mentors with a suggested mentorship style and self-assessment activities to help uncover their typical broaching style when exploring racial issues with protégés. The evaluations provided are not diagnostic; rather, the activities afford mentors a self-reflection opportunity, which should contribute to the mentor’s own growth, and could positively impact the development of a successful, cross-race mentorship

GMO vs. Non-GMO: Comparing the Addictiveness of Corn in Rats

Genetically modified organisms (GMOs) refer to organisms whose DNA has been altered to produce a certain characteristic. GMOs account for a significant proportion of the crops produced in the United States. Specifically, GMO corn accounted for approximately 88% of all corn grown for human and animal consumption in the year 2012. Previously conducted studies have not uniformly demonstrated the safe use of GMO corn, and no studies have been conducted to analyze the addictiveness of GMO corn. The idea of addiction refers to more than just a physical dependence, but to a psychological dependence on something as well. Addiction is sometimes accompanied by compulsive, uncontrollable behaviors that can interfere with other activities and which increase in intensity as there is an increase in access to the substance. Because food addiction is implicated in the prevalence of obesity and its associated pathologies, identifying addictiveness in GMO products may lead to changes in crop production, food production, and use. This study will compare the addictive behaviors of rats who are fed GMO corn. The rats will be randomly divided into three groups. Each group will be fed a diet containing a portion of corn consisting of 0%, 50%, or 100% GMO corn, respectively, for 28 days. After the 28 day treatment period, the rats will be fed a corn-free diet for 10 days. The assessments will include both cage food consumption and body weight measurements taken during both the treatment and withdrawal periods, and behavioral symptoms observed in an open field test during the withdrawal period. The presence of withdrawal indicators will be scored for each rat. The scores will then be compared between the groups using a repeated measures ANOVA test

GMO vs. Non-GMO: Comparing the Addictiveness of Corn in Rats

Genetically modified organisms (GMOs) refer to organisms whose DNA has been altered to produce a certain characteristic. GMOs account for a significant proportion of the crops produced in the United States. Specifically, GMO corn accounted for approximately 88% of all corn grown for human and animal consumption in the year 2012. Previously conducted studies have not uniformly demonstrated the safe use of GMO corn, and no studies have been conducted analyzing the addictiveness of GMO corn. The idea of addiction refers to more than just a physical dependence, but to a psychological dependence on something as well. It is sometimes accompanied by compulsive, uncontrollable behaviors that can interfere with other activities and which increase in intensity as there is an increase in access to the substance. Because food addiction is implicated in the prevalence of obesity and its associated pathologies, identifying addictiveness in GMO products may lead to changes in crop production, food production, and use. This study will compare the addictive behaviors of rats who are fed GMO corn. The rats will be randomly divided into three groups. Each group will be fed a diet containing a portion of corn consisting of 0%, 50%, or 100% GMO corn, respectively, for 28 days. After the 28 day treatment period, the rats will be fed a corn-free diet for 10 days. The assessments will include both cage food consumption and body weight measurements taken during both the treatment and withdrawal periods, and behavioral symptoms observed in an open field test during the withdrawal period. The presence of withdrawal indicators will be scored for each rat, and the scores will be compared between the groups using a repeated measures ANOVA test

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus

Relationship Between Foveal Cone Specialization and Pit Morphology in Albinism

Purpose.Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism. Methods. We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured. Results. We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism. Conclusions. Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue

The Reliability of Parafoveal Cone Density Measurements

Background Adaptive optics scanning light ophthalmoscopy (AOSLO) enables direct visualisation of the cone mosaic, with metrics such as cone density and cell spacing used to assess the integrity or health of the mosaic. Here we examined the interobserver and inter-instrument reliability of cone density measurements. Methods For the interobserver reliability study, 30 subjects with no vision-limiting pathology were imaged. Three image sequences were acquired at a single parafoveal location and aligned to ensure that the three images were from the same retinal location. Ten observers used a semiautomated algorithm to identify the cones in each image, and this was repeated three times for each image. To assess inter-instrument reliability, 20 subjects were imaged at eight parafoveal locations on one AOSLO, followed by the same set of locations on the second AOSLO. A single observer manually aligned the pairs of images and used the semiautomated algorithm to identify the cones in each image. Results Based on a factorial study design model and a variance components model, the interobserver study\u27s largest contribution to variability was the subject (95.72%) while the observer\u27s contribution was only 1.03%. For the inter-instrument study, an average cone density intraclass correlation coefficient (ICC) of between 0.931 and 0.975 was calculated. Conclusions With the AOSLOs used here, reliable cone density measurements can be obtained between observers and between instruments. Additional work is needed to determine how these results vary with differences in image quality