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  Structure function correlation of ERG photopic negative response (PhNR) and OCT Buchs Membrane Minimum Rim Width (BMO-MRW) in Primary Open Angle Glaucoma (POAG)

  Carim-Sanni, Ridwan (2022-12)

  The Photopic Negative Response is a component of the light-adapted electroretinogram (ERG) that is reduced in glaucomatous eyes and the Bruch’s Membrane Opening - Minimum Rim Width (MRW) than Retinal Nerve Fiber Layer (RNFL) thickness are two structural measures of retinal ganglion cell related structures that are disrupted in glaucomatous eyes. The purpose of our investigation was to determine whether the PhNR amplitude in primary open angle glaucoma patients is better correlated with Bruch’s Membrane Opening - Minimum Rim Width (MRW) than Retinal Nerve Fiber Layer (RNFL) thickness. Methods: Full-field Photopic Flash ERGs to brief red flashes delivered on a rod-saturating blue background were recorded from one eye of glaucoma patients (N=10) and age-matched controls (N=10) using an electrophysiological system from Diagnosys (Lowell, MA). The PhNR and b-wave responses of the ERG was plotted as a function of test flash strength and fitted with a generalized Naka-Rushton equation to derive values for saturated amplitude, slope and semi-saturation constant. BMO-MRW and peripapillary RNFL thickness were measured from the same eyes using a Spectral-Domain Optical Coherence Tomography system (Spectralis SD-OCT, Heidelberg Inc, Germany). Visual field sensitivity was assessed with the Humphrey Visual Field Analyzer 24-2 SITA standard test (Carl Zeiss Meditec, USA). ERG Naka-Rushton fit parameters were compared between glaucoma patients and age-matched controls. Linear regression analysis was used to study the correlation of significant fit parameters with BMO-MRW, RFNL and average visual field sensitivity. Results: Of the three different Naka-Rushton fit parameters derived for the PhNR and b-wave only the saturated amplitude of the PhNR was significantly different between glaucomatous and control subjects (p=0.000002). The PhNR saturated amplitude was significantly correlated only with with BMO-MRW in control eyes (r=0.74, m=0.1, p=0.0002) and in glaucomatous eyes showed a better correlation with BMO-MRW (r=0.91, m=0.05, p=0.0002) than with RNFL thickness (r=0.7, m=0.18, p=0.03). PhNR saturated amplitude was also correlated with average behavioral visual sensitivity in glaucomatous eyes (r=0.72, m=29.9, p=0.02). Conclusion: The variance in PhNR amplitude in control and glaucomatous eyes is better accounted for by BMO-MRW than RNFL thickness. This finding may reflect an optic nerve head and prelaminar optic nerve being the locus of PhNR generation as well as early pathogenic events in glaucoma.
• Neural Mechanisms of Luminance Perception

  Rahimi Nasrabadi, Hamed (2022-12)

  Visual animals evolved to efficiently encode luminance increments and decrements with ON and OFF visual pathways. Recent work from our lab indicates that these ON and OFF pathways segregate in primary visual cortex, function relatively independently from each other and process spatial-temporal contrast differently. In my thesis, I investigate the role of ON and OFF cortical pathways in processing luminance contrast and I apply my research findings to image processing and the eye clinic. In the first chapter, I record neural activity from cat primary visual cortex with multielectrode arrays and human visual cortex with electroencephalography. I use these approaches to measure visually evoked cortical responses from ON and OFF pathways to stimuli with different contrast polarity (light or dark) and luminance range (maximum-minimum or standard deviation of luminance distribution). I demonstrate that ON and OFF pathways have different contrast response functions and the differences increase with luminance range. I also demonstrate that these ON-OFF differences are needed to efficiently sample distributions of light and dark contrast in natural scenes. I use my findings to develop a new algorithm of ON-OFF image processing to reproduce more accurately luminance contrast in image photography. In the second chapter, I develop a new test of ON-OFF perimetry in a head-mounted visual display to measure human visual performance for detecting light and dark stimuli at different contrasts and eccentricities. My measurements demonstrate that the relative dominance of ON and OFF pathways is strongly dependent on contrast. At low contrasts, humans are more accurate and faster at detecting light stimuli (ON pathway dominance) but, as contrast increases, they become more accurate and faster at detecting dark stimuli (OFF pathway dominance). I show that multiple light/dark ratios of visual dominance based on performance and reaction time are strongly correlated with stimulus contrast and eccentricity. My results provide new insights on the neuronal mechanisms underlying the perception of luminance contrast and may help to advance computing strategies for image processing and tools to evaluate visual function in the eye clinic.
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  A Theory of Cortical Map Formation in the Visual Brain

  Najafian, Sohrab (2022-12)

  There are about 3 million afferents going from retina to our primary visual cortex through the lateral geniculate nucleus (LGN) of the thalamus. The thalamic afferents form clusters in visual cortex based on the stimuli to which they respond. There are afferent clusters based on retinal spatial arrangement (retinotopy), eye of input (ocular dominance), orientation preference, and light and dark polarity (ON and OFF). The similarities in the pattern organization of afferents in different species suggests a general mapping rule in the development of primary visual cortex. It has been suggested that the thalamocortical pathway is the origin of these maps (Kremkow and Alonso, 2018), but there are still many open questions regarding the functionality, interrelations, and underlying developing mechanisms of these maps. In the first part of this study, I investigated the relationship between the maps of retinotopy and ocular dominance. I explored the underlying reason behind the diversity of ocular dominance columns patterns in the primary visual cortex of different species. I found that the irregularity in the morphology of ocular dominance columns could be explained by local variations in the retinotopic map of different animals. In the second part of the study, I propose a general theory of cortical map formation that provides a biologically plausible mechanism of map development. The main idea of the theory is that the organization of visual cortical maps in different species is determined by the sampling density of the afferents responding to the same point of visual space. As the number of afferents per visual point increases, the visual cortex becomes larger to accommodate the increased number of inputs. Consequently, the input afferents sort not only by spatial location but also by other stimulus features like eye of input and contrast polarity. I test my theory with a computational model that compares computer simulations with experimental data. The model has three main developing stages: 1- retina, 2- cortical subplate, and 3- mature cortex. The result of the model is consistent with a large body of experimental evidence in the literature and our electrophysiological measurements from cat primary visual cortex. The model also allows simulating the cortical map of different animals and could help to guide the implantation of cortical prosthesis in the future to cure blindness.
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  Digital Eye Strain and Repeated Clinical Testing

  Chen, Tiffany Ying-Hsuan (2022-12)

  "Purpose: The use of digital devices has increased substantially over the past decades across all age groups for educational, career and leisure purposes. Although a high prevalence of Digital Eye Strain (DES) has been well established, especially during the recent pandemic, little is known about the association between repeated clinical testing and DES symptoms. The aim of this study was to determine whether symptoms of DES are associated with repeated measurements of standard clinical near-vision tests. Method: The study was performed on 30 young, normally-sighted individuals. Each participant completed 3 sessions to test accommodation (monocular facility, push-up amplitude), vergence (near point of convergence (NPC), near heterophoria) and accommodative-vergence interaction (AC/A ratio, binocular accommodative facility). Participants performed a cognitively demanding reading task from a tablet computer positioned at 33cm for 20 minutes. Repeated clinical measurements (3 readings) were taken both before and immediately after the reading task. Additionally, subjects completed a questionnaire regarding ocular and visual symptoms prior to and immediately after the reading period. Results: While a statistically significant difference in pre- and post-task DES symptom scores was observed (p < 0.01), no significant task-induced change in accommodation, vergence and accommodative-vergence measurements were found. Furthermore, there was no significant difference between the three consecutive readings for any of the pre- or post-task clinical parameters. Conclusion: These results indicate that repeated measurements of standard clinical near-vision tests are not associated with Digital Eye Strain (DES) symptoms. Additionally, no significant difference between the three repeated pre- or post-task measurements was found. "
• Effects of Mild Traumatic Brain Injury (mTBI) on Retinal Structure, Function, and Pupillary Light Responses

  Toan, Trinh (2023-08-01)

  Purpose: Evaluate the sensitivity and light adaptation characteristics of ipRGC-mediated PLR and how they are altered in the dark and under different backgrounds with direct pupil stimulation in patients with mTBI. Methods: Direct pupillary light reflex (PLR) to blue light (peak λ = 440nm, FWHM = 20nm) was measured from the dominant eye, the other eye was fully occluded, of 12 control adult subjects (ages 42.2 ± 17.0 years) and 12 chronic mTBI patients (ages 35.4 ± 12.8 years) using LiveTrack pupilometer module and an infrared camera (30Hz) inside a LED-driven Ganzfeld system (Espion V6 ColorDome, Diagnosys LLC, Lowell, MA). The study consisted of two protocols: (1) The intensity series included 19 steps of increasing intensity ranging from 0.001 to 198 cd/m2, was completed first in sequence after 5 minutes of initial dark adaptation, and 2 minutes between test flashes. A test blue flash stimulus with a duration of 1 second was used, and the pupil response were recorded for 7.5 seconds. Between each successive step, 2 minutes of dark adaption was allowed. (2) The background intensity series, consisted of 7 steps, ranging from 0 to 10 cd/m2, was completed thereafter with test flash of 120 cd/m2 on top of the background. Pupil diameter measurements were made following 5 minutes of initial dark-adaptation, and first on a dark background with a 120 cd/m2 test flash for a duration of 1 second. The subjects adapted for 2 minutes to each subsequent background intensity. The same bright, blue test flash of 120 cd/m2 was used on top of each background intensity. The 6-second post-illumination pupil response (PIPR) amplitudes were extracted at 6 seconds after stimulus offset, and averaged over a 100ms window (i.e., between 6950ms and 7050ms). The peak or maximal pupil constriction amplitude was measured at the trough from baseline. A stimulus intensity response was plotted for the PIPR and peak percent reduction from baseline across all 19 intensities. The intensity series PIPR and peak data was fitted to the Naka-Rushton equation of the form V(I) = (Vmax * In) / (In + Kn) to derive the saturated amplitude (Vmax), slope (n) and semisaturation constant (K). The values of the fit parameters were compared between control and mTBI groups. For the background series, the baseline pupil diameter, PIPR, and peak parameters were extracted from the 7 steps and compared between controls and mTBI patients. Wilcoxin rank sum test was used to compare the corresponding parameters between mTBI and controls. P values less than 0.05 were considered statistically significant. Results: The PIPR was significantly reduced in mTBI patients relative to controls through both the intensity and background series, indicating a reduction in luminance gain of ipRGCs. In addition, the baseline pupil diameter following 2 or 5-minutes of dark-adaptation and at the end of 2-minutes of light adaptation over a 5-log unit range of background intensities (0.0001-10 cd/m2) was larger (i.e., less constriction) for mTBI patients, suggesting an underlying pathophysiology of the ipRGCs, reaffirming the dysfunction of the luminance gain control. Conclusions: The reduction in the PIPR and the larger baseline pupil responses in patients with mTBI insinuated an underlying pathophysiology that may reflect a dysfunction of ipRGC and its luminance gain control mechanism especially when exposed to long duration light stimuli. Therefore, evaluating the baseline diameter at 2 minutes following light exposure on a series of background intensities may prove to be clinically more useful for identifying retinal abnormalities in mTBI.
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  The Relationship Between Meibomian Gland Morphology, Dry Eye Disease, and Electronic Device Use in Pediatric Patients

  Ribolla, Sofia (2022)

  "Purpose: The purpose of this systematic study was to establish preliminary comparisons of various morphological and clinical parameters between dry eye and normal subjects in a pediatric cohort. Methods: Children aged 5-17 were recruited for the study with no previous clinical diagnosis of dry eye disease (DED) or meibomian gland dysfunction (MGD). Diagnostic criteria for DED consisted of positive scoring on at least two of three components; subjective symptoms, abnormal tear function, and vital staining. All subjects completed SPEED questionnaires to assess dry eye symptoms; scores above 5 indicated positive symptomology. Tear film and ocular surface integrity were inspected using fluorescein and lissamine green dye with slit lamp miscroscopy. Corneal fluorescein, as well as temporal and nasal conjunctival lissamine green staining was graded from 1-4 (0=no staining; 4=coalesced). A staining score of more than 4 points across all 3 sections indicated positive vital staining. Abnormal tear function was defined by a TBUT ≤5s. Meibomian gland morphology, lipid layer thickness, and blink patterns were evaluated with the use of a Lipiview Interferometer. The 5-point meiboscale for gland atrophy was used for dropout grading, while tortuosity was defined by number of glands with ≥45° angles. Tear volume assessment was completed with phenol red test. Questionnaires administered to both the child and family member were used to assess electronic device usage in order to screen for possible associations with average daily screen time and aforementioned parameters. Results: A total of 24 subjects participated in the study. Dry eye was found in 41.7% of the subjects. Presence of meibomian gland dropout and tortuosity were 70.8% and 87.5% respectively. Dropout was significantly higher in the dry eye group (p=0.016), although tortuosity was similar between both groups (p=0.93). Tear breakup times were significantly lower in the dry eye group (5.30s vs 9.66s; p<0.001) along with total staining scores (8.00 vs. 3.21; p=0.043). Blink behavior and measurements of lipid layer thickness (LLT) did not vary between the two groups; partial blink ratios were 0.62 and 0.67 for DED and normal groups respectively (p=0.76), and lipid layer thicknesses were 55.9nm and 57.43nm (p=0.84). Electronic device use did not vary significantly between the two groups (p=0.99). Screen time was significantly correlated with higher rate of partial blinks (r=0.84). Higher lipid layer thickness significantly predicted higher partial blink fraction in the left eye (p=0.39) and approached significance in the right eye (p=0.08). Conclusion: The present study provides a current baseline data on ocular surface characteristics and meibomian gland anatomy in healthy children with clinically dry eye vs. those without dry eye. Our results indicate that MGD and DED are highly inter-related at a much earlier age than previously acknowledged, and that the significant rise in pediatric variations of DED represent a worthwhile cause for investigation into long-term risk factors for disease progression. Better understanding of baseline ocular surface and tear film characteristics will be crucial to identify the impact increasingly prevalent risk factors, such as visual device use, myopia interventions, and other changing environmental factors might have on the pediatric population."
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  Complexity of mental geometry for 3D pose perception

  Guo, Crystal (2022-06-13)

  Biological visual systems rely on pose estimation of three-dimensional (3D) objects to understand and navigate the surrounding environment, but the neural computations and mechanisms for inferring 3D poses from 2D retinal images are only partially understood, especially for conditions where stereo information is insufficient. We previously presented evidence that humans use the geometrical back-transform from retinal images to infer the poses of 3D objects lying centered on the ground. This model explained the almost veridical estimation of poses in real scenes and the illusory rotation of poses in obliquely viewed pictures, including the pointing at you phenomenon. Here we test this model for 3D objects in more varied configurations and find that it needs to be augmented. Five observers estimated poses of inclined, floating, or off-center 3D sticks in each of 16 different poses displayed on a monitor viewed straight or obliquely. Pose estimates in scenes and pictures showed remarkable accuracy and agreement between observers, but with a systematic fronto-parallel bias for oblique poses. When one end of an object is on the ground while the other is inclined up, the projected retinal orientation changes substantially as a function of inclination, so the back-transform derived from the object’s projection to the retina is not unique unless the angle of inclination is known. We show that observers’ pose estimates can be explained by the back-transform from retinal orientation only if it is derived for close to the correct inclination. The same back-transform explanation applies to obliquely viewed pictures. There is less change in retinal orientations when objects are floated or placed off-center but pose estimates can be explained by the same model, making it more likely that observers use internalized perspective geometry to make 3D pose inferences while actively incorporating inferences about other aspects of object placement.
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  Feasibility and applicability of a clinical assessment of both the ON and OFF pathways in patients with glaucoma and controls.

  Moore-Stoll, Veronica (2022-05-03)

  "Purpose: To assess the feasibility and clinical utility of a head-mounted, On/Off perimetry test and to investigate the effect of early to moderate glaucoma on reaction time and accuracy to ON and OFF perimetric stimuli. Methods: We tested one eye each of 9 patients with early to moderate primary open angle glaucoma (mean = 71.88 years, std = 5.17), 9 visually-normal control patients of a similar age (mean = 63.88 years, std = 5.17 ) , and 9 visually-normal optometry students (ages 22-25 years). We used a head mounted display equipped with an eye tracker (HTC VIVE embedded Tobii). Custom software (Unity, version 2017) was used to create the stimuli and a library provided by Tobii Pro was used to measure eye movements at 120 Hz. Stimulus size changed as a function of eccentricity using a power law relationship: stimulus size= minimum scale*(eccentricity/5)^α. Eye movements were restricted to a central circle with a 2.5 degree radius. Stimulus contrast was initially set to 100%. A single test comprised of 579 trials, including 51 catch trials, presented at 90 different positions in the visual field. Each test location was repeated 3 times for both light and dark stimuli, with 6 repeats in each of two blind spot positions. Results: Our results demonstrate asymmetry between the two achromatic visual transduction pathways. These results support previous findings that dark targets elicit a faster and more accurate response than light targets, when presented on binary background noise. Our results extend previous work by demonstrating that the two pathways remain asymmetrical in eccentricities up to 30 degree from fixation. We also show that the relationship between the percentage of correct responses for ON pathway and OFF pathway stimuli follows a power function, wherein glaucoma and controls overlap (R2=0.842) . This overlap decreases when we quantify only the subthreshold (unseen) increment targets in a linear relationship (R2=0.7074). All controls had less than 12% of subthreshold increment targets whereas the percentage of subthreshold targets was higher for 75% of the glaucoma subjects, even in early stages of the disease. CONCLUSION We have demonstrated that ON/OFF perimetry is feasible in a VR environment and confirmed an asymmetry between the ON and OFF pathways in patients with glaucoma and control patients in both central and peripheral visual fields. We measured on-pathway deficits in patients with limited loss of visual sensitivity which may improve detection of early disease. Future work will focus on optimizing stimulus parameters to improve the sensitivity and specificity of this test."
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  Effects Of Correcting Fixation Disparity On Digital Eye Strain

  Saksena, Sanjana (2022-04-20)

  Digital Eye Strain (DES) is a widespread and highly prevalent condition whose incidence appears to be rising during the present pandemic. It comprises a range of visual and ocular symptoms which occur after viewing a digital screen for an extended period of time. Previous work from our laboratory has shown the magnitude of fixation disparity to be the only clinical parameter that is significantly correlated with DES symptoms. Therefore, this study sought to determine whether correcting the underlying fixation disparity will significantly reduce DES symptoms. Thirty young, visually-normal students were required to read randomly generated words from a digital tablet device for 20 minutes. Three different trials were performed, with the subject wearing either: (i) the prism that corrected their fixation disparity, (ii) the same magnitude of prism as for condition (i) but with the opposite base direction or (iii) a near addition lens that corrected the fixation disparity. Immediately after the reading task, subjects rated their ocular and visual symptoms on a questionnaire. There was no significant difference between the mean symptom scores for the three conditions. However, this may be due, in part, to the small number of subjects encountered with large values of fixation disparity. Future studies should further examine the range of oculomotor responses associated with DES in order to provide appropriate treatment options.
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  Library renovation: From setbacks to success.

  Wells, Elaine (Research Caucus of the Medical Library Association, 2021-02-25)

  The journey started at a 2016 meeting of the college’s Learning Resources Committee, which I chair as Library Director, A student representative casually commented that our Library looked “dated”. Not that we actually WERE dated, we have electronic resources, 24/7 remote access, printers, scanners, wireless, and a state-of-the-art Library Management System. However, through the eyes of our young student, the Library looked “like something from the 1970s.” Anyone who has lived through that decade’s will know that was not meant as a compliment. The student’s criticism prompted the Dean of Academic Affairs, who sat in on the meeting, to ask when the Library had had its last “facelift.” That was an easy one to answer - as far as I knew…never. And I’ve been here over 20 years. Just like that, a renovation was born. How hard could this be? I would query the students on what a suitable update might look like, get a budget, buy some new furniture, and go back to the business of being a librarian rather than an interior designer. Spoiler alert: not so fast.
• Color Transparency: Geometry, Motion, Color, Scission, and Induction

  Huang, Zhehao (2024-03-30)

  Objects that pass light through are considered transparent, and we generally expect that the light coming out will match the perceived color of the object. However, when the object is placed on a colored surface, the light coming back to our eyes becomes a composite of surface, illumination, and transparency properties. Despite that, we can often perceive separate overlaid and overlaying layers differing in colors. How neurons separate the information to extract the transparent layer remains unknown, but physical characteristics of transparent filters generate geometrical and color features in retinal images which could provide cues for separating layers. We estimated the relative importance of such cues in a perceptual scale for transparency, using stimuli in which X or T-junctions, different relative motions, and color consistency, cooperated or competed in forced-preference psychophysics experiments. Maximum-likelihood Thurstone scaling revealed some new results: moving X-junctions increased transparency compared to static X-junctions, but moving T-junctions decreased transparency compared to static T-junctions by creating the percept of an opaque patch. However, if the motion of a filter uncovered a dynamically changing but stationary pattern, sharing common fate with the surround but forming T-junctions, the probability of seeing transparency was almost as high as for moving X-junctions, despite the stimulus being physically improbable. In addition, geometric cues overrode color inconsistency to a great degree. Finally, a linear model of transparency perception as a function of relative motions between filter, overlay, and surround layers, contour continuation, and color consistency, quantified a hierarchy of latent influences on when the filter is seen as a separate transparent layer. Previous measurements of color scission have limitations. The color adjustment to match the target color is relatively accurate but time consuming and suffers from long time adaptation bias. Force-choice judgment is quick and free from adaptation effect, but the selection of choices can be the source of bias. We examine the observers’ ability to estimate filter color with transparency with our improved method: we ask observers to make a judgement of the transparency region being red or green (or, blue/yellow). By doing this we found the neutral point of the filter that the observers think colorless. The result showed that, in color consistent conditions, though biased by the background or individual preference, the observers’ measured neutral filter settings were close to the colorless filter, showing relatively good color scission. In the color inconsistent conditions, the observers matched the overlaid region to a neutral color, as if the observers were attributing the average color of the overlaid region completely to the transparency. Veridicality of scission varied little in the color consistent conditions, despite the large variation in degree of perceived transparency. An exception to the rule that only one color is seen at every retinotopic location happens when a bounded colored transparency or spotlight is seen on a differently colored surface. Despite the spectrum of the light from each retinotopic location being an inextricable multiplication of illumination, transmission, and reflectance spectra, we seem to be able to scission the information into background and transparency/spotlight colors. Visual cues to separating overlay and overlaid layers have been enumerated, but neural mechanisms that extract veridical colors for overlays have not been identified. Here, we demonstrate that spatial induction contributes to color scission by shifting the color of the overlay toward the actual color of the filter. By alternating filter and illumination spectra, we present naturalistic simulations where isomeric disks appear to be covered by filters/spotlights of near veridical colors, depending solely on the surrounding illumination.
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  Objective Assessment of Retinal Ganglion Cell Function in Glaucoma

  Joshi, Nabin (2017-09-25)

  Glaucoma refers to a group of diseases causing progressive degeneration of the retinal ganglion cells. It is a clinical diagnosis based on the evidence of structural damage of the optic nerve head with corresponding visual field loss. Structural damage is assessed by visualization of the optic nerve head (ONH) through various imaging and observational techniques, while the behavioral loss of sensitivity is assessed with an automated perimeter. However, given the subjective nature of visual field assessment in patients, visual function examination suffers from high variability as well as patient and operator- related biases. To overcome these drawbacks, past research has focused on the use of objective methods of quantifying retinal function in patients with glaucoma such as electroretinograms, visually evoked potentials, pupillometry etc. Electroretinograms are objective, non-invasive method of assessing retinal function, and careful manipulation of the visual input or stimulus can result in extraction of signals particular to select classes of the retinal cells, and photopic negative response (PhNR) is a component of ERG that reflects primarily the retinal ganglion cell function. On the other hand, pupillary response to light, measured objectively with a pupillometer, also indicates the functional state of the retina and the pupillary pathway. Hence, the study of both ERGs and pupillary response to light provide an objective avenue of research towards understanding the mechanisms of neurodegeneration in glaucoma, possibly affecting the clinical care of the patients in the long run.
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  Gap Junctional Coupling between Retinal Amacrine and Ganglion Cells Underlies Coherent Spike Activity Integral to Global Object Perception

  Roy, Kaushambi (2017-08)

  Coherent spike activity between neighboring cells is a ubiquitous phenomenon exhibited by ensembles of neurons throughout the central nervous system, including the retina. In addition to the robust coherent activity between neighboring retinal ganglion cells (RGCs), there is evidence that widely separated RGCs can also show correlated spiking. These long range correlations can be evoked by large, contiguous light stimuli, but not to smaller, discontinuous objects. It has thus been posited that long range spike correlations between distant RGCs encode information critical to global object perception. Since the wide separation of the RGCs precludes common excitatory drive from bipolar cells, the mechanism underlying long range concerted activity has remained elusive. Most RGCs show gap junctional coupling to polyaxonal amacrine cells (PACs), which maintain extensive axonal arbors that can extend >1mm across the retina. The electrical coupling between RGCs and PACs thereby form a plausible circuit that can underlie long range correlated activity in the retina. In the current study we tested this hypothesis by targeting and recording from pairs of widely separated ON α-RGCs in the mouse retina, which are coupled indirectly through intermediary PACs. Pharmacological blockade of gap junctions or genetic ablation of connexin36 (Cx36) subunits eliminated the long range correlated spiking between the α-RGCs. These data indicated that electrical coupling between RGCs and PACs was responsible for the long range spike activity. In contrast, I found that direct, serial RGC-RGC coupling was incapable of supporting long range spike correlations. Finally, behavioral experiments were performed to test whether blockade of retinal gap junctions or ablation of Cx36 attenuates the ability of mice to discriminate large, global objects from small, disjointed stimuli. I found that Cx36 knockout mice indeed have significantly reduced ability to discriminate global objects from smaller discontinuous stimuli as compared to wild type littermates. This reduced perception of global objects was not due to a general reduction in spatial acuity that measured in knockout animals was similar to that for wild type mice. Taken together, our results indicate that long range concerted firing between RGCs, derived from electrical coupling with amacrine cells, encodes information critical to global object perception.
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  The Effect of Multifocal Contact Lenses on Accomodation and Phoria in a Pediatric Population

  Gong, Celia (2017)

  The increasing prevalence of the use of distance-centered multifocal (MF) contact lenses as a method of myopia control in the pediatric population calls for a better understanding of binocularity and accommodation in children wearing these lenses. This was a prospective, randomized, crossover, single visit study that enrolled myopic children with normal accommodation and binocular vision and no history of myopia control treatment. All subjects were fitted with Coopervision Biofinity single vision (SV) and MF (+2.50D center distance add) contact lenses. Accommodative responses (photorefraction) and phorias (Modified Thorington) were measured at 4 distances (>3m, 100cm, 40cm, 25cm). Secondary measures included high and low contrast logMAR acuity, accommodative amplitude, and accommodative facility. Differences between MF and SV contact lenses were analyzed using repeated measures regression and paired t-tests. A total of 16 subjects, aged 10-15 years, completed the study. There was a small decrease in high (SV: -0.08, MF: +0.01) and low illumination (SV:-0.03, MF: +0.08) (both p<0.01) visual acuity, and contrast sensitivity (SV: 2.0 log units, MF: 1.9, p=0.015) with MFs. Subjects were more exophoric at 40cm (SV: -0.41 Δ, MF: -2.06 Δ) and 25cm (SV: -0.83 Δ, MF: -4.30 Δ) (both p<0.01). With MFs, subjects had decreased accommodative responses at distance (SV: -0.04 D; MF: -0.37 D, p=0.02), 100 cm (SV: +0.37 D; MF: -0.35 D, p<0.01), 40 cm (SV: +1.82 D; MF: +0.62 D, p<0.01), and 25 cm (SV: +3.38 D; MF: +1.75 D, p<0.01). There were no significant differences in accommodative amplitude (p=0.66) or accommodative facility (p=0.54). Children wearing MF contact lenses exhibited reduced accommodative responses and more exophoria at increasingly higher accommodative demands than with SV contact lenses. This suggests that children may be relaxing their accommodation and using the positive addition or increased depth of focus from added spherical aberration of the MF lenses. Further studies are needed to evaluate other lens designs, different amounts of positive addition and aberrations, and long-term adaptation to lenses.
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  Mild Traumatic Brain Injury (mTBI) and Photosensitivity: Objective Pupillometric Findings

  Truong, James Q. (2016-06)

  Background Given the extensive neural network of the human, binocular, pupillary system including its sympathetic and parasympathetic innervation, it is plausible that a mild traumatic brain injury (mTBI) could compromise pupillary control, thus causing pupillary asymmetry and dysfunction. Furthermore, presence of such pupillary abnormalities could exacerbate mTBI-related visual symptomatology, such as photosensitivity. There have only been two studies in the area, and they both used monocular pupillometry with only one test condition; hence they were limited. Furthermore, their results were in part equivocal. There remain many unanswered questions (i.e., gaps) in this important field of study including: 1) does mTBI affect the pupillary light reflex (PLR)?, 2) is there an increase in inter-ocular pupillary asymmetry (IOPA) in mTBI?, and 3) are there PLR differences related to one of the most prominent and prevalent dysfunctions resulting from mTBI, namely photosensitivity? Aim The overall aim of the present dissertation was twofold. First, to evaluate comprehensively the effect of mTBI on the human pupillary system, and furthermore to determine if pupillometry could be used as an objective visual biomarker for mTBI. Second, to evaluate comprehensively the effect of photosensitivity on the human pupillary system, and furthermore to determine if pupillometry could be used as an objective biomarker for photosensitivity. Methods The binocular pupillary light reflex was evaluated in mTBI, and it was compared to normal individuals, with and without photosensitivity, under a range of test conditions. Nine pupillary parameters (maximum, minimum, and final pupillary diameter; latency; amplitude; and peak and average constriction and dilation velocities) and 6 stimulus conditions (dim pulse, dim step, bright pulse, bright step, bright red step, and bright blue step) were assessed in 32 adults with mTBI (21-60 years of age) and compared to 40 normals (22-56 years of age). The Neuroptics, infrared, DP-2000 binocular pupillometer was used (30Hz sampling rate; 0.05mm resolution) with binocular stimulation and recording. Results and Discussion 1. Inter-ocular pupillary asymmetry: There were no statistical differences in either static or dynamic inter-ocular pupillary asymmetry (IOPA) between the normal and mTBI groups. Thus, the pupillary effects of mTBI appear to be symmetrical rather than asymmetrical in nature, which suggests post-chiasmal involvement. The mean average (across groups) static IOPA was 0.26 + 0.20mm or 4.17 + 3.29%. The mean average dynamic IOPA was dependent on the light stimulus condition, with the average across all test conditions and groups being 0.11 + 0.10mm or 1.84 + 1.70%. 2. Pupillometry in mTBI: mTBI has been reported to cause the pupillary light reflex (PLR) to be globally attenuated (i.e., slower in onset and more sluggish in response dynamics). The present results showed that there were many statistically significant differences (p < 0.05) in the PLR parameters between the mTBI and normal groups. Furthermore, different test conditions allowed for discrimination of different parameters between the two groups. For any of the given six test conditions, 5 to 8 of the 9 pupillary parameters were statistically different (p < 0.05) between the two groups. The overall trends revealed that the mTBI cohort had longer constriction latency, slower constriction and dilation velocities, and smaller pupillary diameters (baseline, minimum, and 6PSPD). The most consistent and robust pupillary parameters that differentiated between the two groups were the pupillary diameters (maximum, minimum, and 6SPSD; p < 0.01 under all 6 test conditions), and peak dilation velocity (p < 0.02, under all applicable conditions). This suggests that mTBI adversely affects both the sympathetic and parasympathetic systems, however, the effect appears to be greater on the sympathetic system. 3. Pupillometry in photosensitivity: There were statistically significant differences (p < 0.05) in the PLR parameters of those with versus without photosensitivity in both groups. Interestingly, these differences depended upon whether the photosensitivity was mTBI related. Those with mTBI and photosensitivity manifested six significant differences (p < 0.05) as compared with those with mTBI cohort without photosensitivity: larger baseline diameter, larger minimum diameter, faster peak dilation velocity, faster T50 and T75 recovery times, and a larger pupil diameter at 6 seconds post-stimulus. Normal (non-mTBI) subjects with photosensitivity exhibited four significant differences (p < 0.05) as compared with their normal cohort without photosensitivity: larger constriction amplitude, faster average constriction
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  Exploring the veridicality of shape-from-shading for real 3D objects

  Bartov, Jenny (2016-05)

  Despite the large number of shape-from-shading studies, the degree of veridicality with which observers perceive real 3D objects from shading cues has not been examined. Six observers viewed semicircular, triangular and trapezoidal corrugations in depth made from gray cardboard of approximately uniform reflectance, presented in a fronto-parallel plane. The object, placed inside a box, was illuminated solely from its top-left or left by a point light source. The corrugations were seen through an aperture that masked their terminating contours and the light source. Observers were asked to draw the depth profile of the object as if it were seen from above. Using a computer mouse, they drew on a computer screen placed just below the object. They also indicated the orientation of the object and the location of the light source. In the first condition, the objects were viewed monocularly; in the second, a white matte sphere was placed in front of the objects to help in locating the light; in the third, the task was repeated with binocular viewing. Drawings revealed that observers were quite accurate in inferring the objects’ shapes when viewing binocularly. There was more variability among the observers when objects were viewed monocularly, with some systematic trends: 1. Most observers were able to recreate the veridical shapes despite monocular viewing. 2. The drawn shapes often differed from the shape of the luminance variations across the objects, thus rejecting heuristics such as “dark is deeper”. 3. In the absence of cues to light direction, observers did not tend to resort to a “light from above” prior. 4. While binocularity heavily aided the extraction of the true shapes, knowledge of the illuminant direction did not. However, even though the exact location of the light source did not aid in extracting 3D shape, when oriented at a horizontal level, the light source did aid in perceiving 3D orientation.
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  Objective assessment of visual dysfunction in the acquired brain injury (ABI) population using the visual-evoked potential (VEP)

  Yadav, Naveen K. (2014-07-09)

  Purpose: To assess quantitatively and objectively selected visual dysfunctions in patients with mild traumatic brain injury (mTBI) (i.e., increased abnormal visual motion sensitivity (VMS), attentional deficits) and stroke (i.e., hemianopic visual field defects) by using empirically-derived, optimized pattern visual evoked potential (VEP) parameters derived from our laboratory. Furthermore, the goal was to develop simple and reliable clinical VEP protocols to assess the aforementioned visual dysfunctions in acquired brain injury. Methods: Four experiments were performed binocularly with full refractive correction using an objective, pattern VEP technique. Experiments #1-3 included both visually-normal (VN) adults and adults with mTBI, all ages 18-70 years. Experiment #4 included adult patients with stroke and hemianopic visual field defects, all ages 18-70 years. The following tests and stimulus conditions were used in Experiments #1-4: Experiment #1 – central field VEP with 10, 20, and 40 min arc check sizes at low (20%) and high (85%) contrast levels; Experiment #2 – central field VEP (baseline), binasal occlusion only (BNO), base-in prism (BI) only (4 pd total), and BNO with 4 pd BI; Experiment #3 – central field VEP (eyes open (EO), baseline), eyes-closed (EC, “relaxed”), and eyes-closed number counting (ECNC, “increased attentional state”); Experiment #4 – central field VEP, intact hemi-field only, and hemianopic field only. Results: The followings results were found: Experiment #1 – The 20 min arc check size provided the largest VEP amplitude and normative latency values at both contrast levels in both the VN and mTBI groups. These optimal parameters were then used to measure VEP responses in Experiments #2-4. Experiment #2 – With BNO alone, the VEP amplitude was larger in individuals with mTBI (90%) and smaller in the VN (100%) groups, as compared to other two test conditions and baseline. In addition, with BNO only, those with mTBI demonstrated improvement in their visual impressions and in performing specific sensorimotor tasks. Experiment #3 – Objectively-based alpha attenuation ratio (AR = EC ÷ EO, ECNC ÷ EC) was able to detect, assess, and differentiate between mTBI with versus without an attentional deficits, as well as between VNs. These objective AR findings were correlated with the subjective Adult ADHD Self-Report Scale (ASRS) questionnaire scores. Experiment #4 – The group and individual VEP findings showed that the central field and the intact hemi-field VEP amplitudes were larger than found in the hemianopic field. Moreover, these objective findings were correlated with the subjective clinical perimetric results. Conclusions: The optimized VEP parameters provided quantitative, rapid, reliable, and repeatable responsivity in all experiments. These findings demonstrated that the conventional pattern VEP could be beneficial for researchers in general, as well as clinicians to differentiate between mTBI versus the VN group with a high probability, and also between mTBI with versus without an attentional deficit. In addition, the VEP could be used clinically to detect and assess hemianopic visual field defects in patients with stroke. Based on these findings, the VEP has the potential to be used as an objective visual system biomarker for the diagnosis of mTBI/concussion, and also as an objective adjunct clinical tool to detect visual field defects in patients with stroke.
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  Reading from an Electronic Reading Device versus Hardcopy Text

  Hue, Jennifer E. (2013-06-24)

  The use of electronic reading devices has become more prevalent. Many individuals of all ages are using personal electronic readers (e.g., Kindle, Nook, E-Reader) in place of hardcopy printed materials. Previous work in our laboratory has demonstrated that symptoms when reading from a computer screen are significantly greater than those experienced when reading printed text. Accordingly, the aim of the present study was to examine both symptoms and task performance when reading from a Kindle e-reading device, and to compare the findings with those from hardcopy, printed materials.
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  Oculomotor rehabilitation for reading dysfunction in mild traumatic brain injury

  Thiagarajan, Preethi (2013-06-04)

  Abstract: Aim Considering the extensive neural network of the oculomotor subsystems, global damage as a result of traumatic brain injury could compromise precise oculomotor control, thus causing reading dysfunction. The aim of the present thesis was to evaluate comprehensively the effect of oculomotor-based vision rehabilitation in symptomatic individuals with respect to nearwork and reading and having a mild traumatic brain injury (mTBI). A wide range of laboratory and clinical parameters related to reading involving vergence, accommodation, and version were tested. Methods Twelve subjects with documented mTBI and nearvision-related symptoms participated in the study. A cross-over, interventional experimental design was used involving true “oculomotor” training and “SHAM” training. Each training protocol was performed for 6 weeks, 2 sessions a week, 45 minutes of actual training per session. During each training session, all three oculomotor subsystems (vergence/accommodation/version) were trained for 15 minutes each in a randomized order. All laboratory and clinical parameters were measured before (baseline) and after true oculomotor (post-OMT) and SHAM (post-SHAM) training. In addition, nearvision-related symptoms were assessed using the Convergence Insufficiency Symptom Survey (CISS) scale. Lastly, subjective attention was measured using the Visual Search and Attention Test (VSAT). iv Results Following true oculomotor training, there was a marked improvement in various laboratory and clinical parameters assessed. Over 80% of the abnormal parameters found at baseline testing were found to significantly improve with training. Dynamics of vergence and accommodation, along with clinically assessed maximum amplitudes, improved markedly. Versional saccadic eye movements demonstrated improved rhythmicity and accuracy. These results together had a significant positive impact on overall reading ability. The improved reading-related oculomotor behavior was reflected in reduction of symptoms. In addition, subjective attention was found to also improve with true oculomotor training. In contrast, none of the aforementioned parameters changed with SHAM training. Conclusions Oculomotor-based vision rehabilitation had a strong positive effect on reading-related oculomotor control. This oculomotor learning effect is suggestive of intact neuroplasticity mechanisms in a compromised brain following TBI.
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  Triptolide Induces Increases in Migration via Mitogen-activated Protein Kinase Phosphatase-1 control of P38 and JNK MAPK Activation

  Parekh, Nili M. (2010-07-16)

  Purpose Triptolide is a Chinese herbal extract known for its anti-inflammatory and immunosuppressive effects in treating chronic inflammatory diseases and tumors. As these attributes promote wound healing, we determined if triptolide enhances corneal wound healing by stimulating human corneal epithelial cell (HCEC) migration through changes in negative feedback regulation by a dual specificity protein Phosphatase (DUSP1) of MAPK signaling mediated effect. Methods SV40-adenovirus-immortalized HCEC were maintained in DMEM/F12. Specific shRNA for MKP-1(DUSP1) and c-jun NH2- terminal kinase JNK-1 were transduced to establish stable cell lines deficient in their respective gene expression. Scratch wound assay was employed to assess cell migration rates by taking time-dependent serial photographs of cells following wound creation. Hydroxyurea (2.5 mM) was also added to the medium to inhibit cell proliferation during the experiment. Cell Titer-Glo® luminescent cell viability assay was used to evaluate cell viability by measuring ATP production by HCEC. Results Triptolide did not affect cell viability up to 10nM and stimulated wound closure through increases in migration. Maximal responses occurred at 1nM. These increases in migration were suppressed below that in the untreated control when p38 or JNK MAPK activation was inhibited. In the MKP-1 knockdown cells, migration was stimulated relative to the control and triptolide failed to augment this response. In JNK-1 knockdown cells, migration is comparable to SV40 wild type cells. In JNK-1 knockdown cells, triptolide mediated increases are diminished completely in the presence of p38 inhibition. Conclusions Triptolide at concentrations up to 10 nM promotes cell migration without compromising cell survival. Such promotion is mediated by loss of MKP-1 negative feedback control of p38 and JNK activation. Therefore, triptolide stimulates cell migration through inhibition of MKP-1 (DUSP1) stabilization induced by kinase mediated phosphorylation.

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