SUNY Optometry Doctoral Dissertation Collection
Recent Submissions
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Functional contributions of ON and OFF pathways to human vision"The human visual system processes light and dark stimuli with separate ON and OFF neuronal pathways that originate in the retina, at the first synapse of the visual system, and remain segregated in the rest of the brain. In animal models, ON and OFF pathways are differently modulated by the spatiotemporal properties of stimuli. In my thesis, I investigate the stimulus modulations of these two pathways in humans and the possible clinical implications of their functional differences. In the first chapter, I record visual images and visuomotor activity in human subjects performing two visual tasks, reading and walking indoors, while wearing Tobii Pro Glasses 2. Reading and walking are known to pose different risks of myopia progression, a visual disorder that blurs vision at far distances. However, the stimulus parameters driving myopia progression remain unclear. To investigate this question, I quantify the visual input to the retina and visuomotor activity during the two tasks. I demonstrate pronounced task differences in the stimulation balance of ON and OFF visual pathways. My results demonstrate that reading reduces central visual stimulation of ON visual pathways and decreases visuomotor activity and reflexes dominated by ON visual pathways. These results support the hypothesis that reading drives myopia progression by under-stimulating ON visual pathways. In the second chapter, I use electroretinography (ERG) to measure the contrast response functions of ON and OFF retinal pathways in humans and further investigate if the two pathways are differently affected by myopia. We have previously demonstrated that ON and OFF pathways have different contrast sensitivity in visual cortex, and that the difference increases with luminance range (defined as the difference between maximum and minimum luminance in an image). Here, I demonstrate that these ON-OFF differences are already present in the human retina and are affected by myopia. I show that myopia is associated with a deficit in ON retinal pathway function that reduces the retinal ability at signaling low contrast and regulating retinal illuminance in bright environments. In the third chapter, I measure spatial frequency tuning of retinal ON and OFF pathways in humans using pattern ERG. Previous studies from our lab demonstrated that, in carnivores and non-human primates, ON and OFF cortical pathways have different spatial frequency tuning. My results demonstrate that these ON-OFF tuning differences are also present in the human retina. I show that retinal responses to light stimuli are tuned to higher spatial frequencies than retinal responses to dark stimuli. High spatial frequencies drive stronger responses from retinal ON pathways whereas low spatial frequencies drive stronger responses from retinal OFF pathways. Overall, my results reveal new insights on the function of ON and OFF retinal pathways in humans, and add to the growing research effort to understand the link between retinal circuitry and myopia. My research may also help to explain why outdoor activity and reading have opposite effects on myopia progression, and lead to novel approaches for myopia control. "
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Neuronal properties, neural populations, and mental geometry in inferring object attributes"In the first chapter, we reveal that while many studies have focused on size invariance concerning physical distance, the constancy or inconstancy of relative size with respect to object pose has been largely overlooked. Our findings demonstrate a systematic underestimation of length for objects oriented toward or away from the observer, whether static or dynamically rotating. While observers attempt to correct for projected shortening using the optimal back- transform, these corrections often fall short, particularly for longer objects that appear more slanted. Incorporating a multiplicative factor for perceived slant into the back-transform model yields a better fit to the observed corrections. In the second chapter, we extend this investigation to obliquely viewed pictures, comparing human performance to the optimal geometric solution. We show that size and shape distortions occur in oblique views, particularly for objects at fronto-parallel poses, leading to significant underestimation. We found that empirical correction functions, although similar in shape to the optimal, are of lower amplitude, likely due to systematic underestimation of viewing azimuth. By adjusting the geometrical back-transform to account for this bias, we achieve better fits to the estimated 3D lengths from oblique views. These results add to the evidence that humans use internalized projective geometry to perceive sizes, shapes, and poses in both real scenes and their photographic representations. The third chapter addresses the perception of rigidity and non-rigidity in rigidly moving objects. We used rotating rigid objects that could appear either rigid or non-rigid to test the contribution of shape features to rigidity perception. Our results show that salient features such as gaps or vertices reinforce the perception of rigidity at slow and moderate speeds, while all configurations appear non-rigid at high speeds. We also demonstrate that motion flow vectors from local ME computation are predominantly orthogonal to the contours of the rings rather than parallel to the rotation direction. A convolutional neural network trained to distinguish flow patterns for wobbling versus rotation showed that motion-energy flows contribute to the perception of wobbling, while feature tracking mechanisms enhance the perception of rotation. Interestingly, circular rings can sometimes appear to spin and roll even without any sensory evidence, an illusion that is mitigated by the presence of vertices, gaps, and painted segments, highlighting the role of rotational symmetry and shape. By combining CNN outputs that prioritize motion energy at high speeds and feature tracking at low speeds, along with shape-based priors for wobbling and rolling, we were able to accurately explain both rigid and non-rigid perceptions across different shapes and speeds (R2=0.95). These findings demonstrate how the cooperation and competition between different classes of neurons lead to distinct states of visual perception and transitions between those states. Finally, the fourth chapter investigates the anisotropy in object non-rigidity, linking it to low-level neural properties in the primary visual cortex. By combining mathematical derivations and computational simulations, we replicate psychophysical findings on non-rigidity perception in rotating objects. Our analysis reveals that perceived shape changes, such as elongation or narrowing of rings, can be decoded from V1 outputs by considering anisotropies in orientation-selective cells. We empirically show that even when vertically rotating ellipses are widened or horizontally rotating ellipses are elongated to match shapes, the perceived difference in non-rigidity decreases, but heightened non- rigidity remains in vertical rotations. By integrating cortical anisotropies into motion flow calculations, we observed that motion gradients for vertical rotations align more closely with physical wobbling, whereas horizontal rotations fall somewhere between wobbling and rigid rotation. This indicates that intrinsic cortical anisotropies play a role in amplifying the perception of non-rigidity when orientation changes from horizontal to vertical. The study highlights the significance of these cortical anisotropies in influencing perceptual outcomes and prompts further exploration of their evolutionary purpose, particularly in relation to shape constancy and motion perception.
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Myopia's Influence on the Retinal Neurovascular Unit and its Implications in Glaucoma"Myopia is an increasingly common refractive error that not only causes distance vision blur, but also poses greater risks of developing ocular pathologies such as choroidal neovascularization, retinal detachments, glaucoma, and various maculopathies1, 2. Myopia prevalence is projected to increase from 28% in 2010 to almost 50% by 2050, and affect almost 5 billion people around the world3, 4. The global myopia epidemic is impossible to deny or ignore, with myopic maculopathies the primary cause of irreversible vision loss worldwide3. Glaucoma is a multifactorial eye disease characterized by irreversible optic neuropathy, progressive visual field deficits, and occasionally intraocular pressure (IOP) elevation; it is the second leading cause of blindness worldwide, and is estimated to affect over 120 million people by the year 20405. There is strong evidence confirming a relationship between myopia and glaucoma, and that myopic patients are more susceptible to glaucomatous degeneration. However, the mechanisms fundamental to this association remain unknown. There exist no early diagnostic markers for preventing myopia-associated glaucomatous onset and development1, 2, which can cause irrevocable structural and functional deficits, subsequently increasing vulnerability of the retina to glaucomatous degeneration. Through the work completed in this thesis, an assessment of components of the retinal neurovascular unit was performed to elucidate the effect of sustained myopia in an experimental non-human primate (NHP) model, and how myopia predisposes the retina to glaucomatous damage due to the effects of myopic eye growth and stretch on the inner retina. Myopia was induced in marmosets using soft single vision contact lens wear of varying refractive errors, while glaucoma was induced via intracameral injection of microbeads, causing angle occlusion and IOP elevation. Successful marmoset models of myopia, glaucoma, and myopic glaucoma were generated. During treatment, measurements of individual retinal layer thicknesses, axial length, and refractive error were gathered, and the density and distribution of retinal ganglion cells, astrocytes, and vasculature via immunohistochemistry (IHC), retinal layer thicknesses via optical coherence tomography (OCT), and functional assessment of cell function via electroretinography (ERG) were performed. Aim 1 investigated the effect of myopia on the retinal vascular template, astrocyte template, and retinal nerve fiber layer (RNFL) thickness in 6-month-old marmosets induced with myopia for four months. The analysis revealed an increase in pan-retinal string vessels and a decrease in peripheral vascular branch points, a decrease in Sox9+ astrocyte density, and increased glial fibrillary acidic protein (GFAP) glial reactivity in myopic eyes compared to age-matched controls. The RNFL was also thinner in myopic eyes compared to age-matched controls, and the relationship between astrocyte density and RNFL thickness known to exist in primates was present in controls, but not in myopic eyes. Aim 2 explored the effect of sustained defocus and aging on the retinal microvascular template of marmosets induced with myopia for four months compared to marmosets induced with myopia for ten months and age-matched controls. The analysis revealed an increased number of string vessels in all four vascular plexi and increased vascular branch points in the parafoveal retina but decreased in the peripapillary and peripheral retinas with myopia progression. Aim 3 examined the effect of sustained myopic eye growth on astrocyte cellular distribution, and its association with inner retinal layer thicknesses in marmosets induced with myopia for 4 months compared to marmosets induced with myopia for 10 months and age-matched controls. Myopic marmosets induced for 10 months experienced exacerbated pan-retinal decreased astrocyte density and increased GFAP-immunopositive spatial coverage, similar RNFL thinning but greater"
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The Role of Astroglial Connexin43 in Experimental Glaucoma.Glaucoma is an irreversible blinding disease due to progressive loss of retinal ganglion cells (RGCs) and their axons. Astrocytes are glial cells that reside in the retinal nerve fiber layer (RNFL) closely to RGC bodies and unsheathe axons in the optic nerve head. Astrocytes play an important role in the pathogenesis of glaucoma. A unique feature of astrocytes is that they are extensively coupled by gap junctions (GJ) composed of connexin 43 (Cx43). In addition, unopposed Cx43 hemichannels can open in pathological conditions and release signaling molecules (e.g., ATP and excess glutamate). The role of astrocytic Cx43 GJ and hemichannels in glaucoma is unclear. Here we studied the effect of Cx43 deletion in astrocytes in normal conditions and in glaucomatous injuries. Results show that deletion of Cx43 does not affect normal retinal function, potentially due to direct coupling of astrocytes to Müller glia. Microbead-induced elevation of IOP increased Cx43 expression and GJ coupling in astrocytes. Importantly, astrocyte-specific deletion of Cx43 markedly reduced RGC death and preserved visual function in glaucomatous mice. Absence of Cx43 in astrocytes also reduced microglial activation in glaucoma but did not affect astrocyte reactivity. Additionally, intravitreal injections of Gap19 peptide, a selective Cx43 hemichannel blocker, markedly increased RGC survival and improved RGC function, indicating a contribution of activated Cx43 hemichannels in glaucoma progression. Therefore, targeting Cx43 hemichannels might be a new therapeutic approach to the treatment of glaucoma.
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Alterations to the structure and function of the retina and choroid in an experimental model of progressive myopiaMyopia is one of the most common ocular disorders. Its onset and progression are characterized by vitreous chamber elongation that puts mechanical strain on the retina and choroid, potentially compromising the integrity and functioning of its cells and presents an increased risk of developing posterior segment complications. The exact relationship with myopic growth remains unclear since most studies describe correlational rather than causal relationships. This thesis presents a comprehensive evaluation of the gross anatomical, cellular and functional changes in a non-human primate model with 6 months of myopia development to understand the effect of myopic growth on the retina and choroid and detect early biomarkers of myopic growth and susceptibility to ocular complications. The thickness of each individual retinal layer, choroidal biometry, ganglion cell (RGC) and astrocyte densities, function, and interrelationship between all measures were assessed using spectral-domain optical coherence tomography, immunohistochemistry and electroretinogram in marmosets. Aim 1 investigated the cause-effect relationship between myopic growth and individual retinal thickness changes measured using SD-OCT. While untreated controls had an overall age-related retinal thickening, the myopic animals had relative thinning of the GCL, IPL, INL, OPL, ONL and relative RPE thickening. Retinal changes in these layers within the near-mid retinal periphery predicted the compensatory refraction and vitreous elongation observed. Aim 2 employed IHC to explore the effect of myopia on the spatial distribution of RGC and astrocytes, as well as glial reactivity, in the ganglion cell complex. The analysis revealed reduced RGC and astrocyte cell densities in the peripapillary retina as well as an increase in global GFAP coverage and GFAP intensity in myopic eyes compared to controls. These cellular changes were associated with the degree of myopic growth. Aim 3 studied inner retina function using the full-field ERG PhNR, and input from bipolar cells (b- and d-wave) in myopic marmosets. Less than 2 weeks into treatment, when treated marmosets had not developed significant changes in eye size or refraction, the b-, d- and PhNR wave amplitudes had decreased compared to controls. These amplitude reductions disappeared as treated marmosets grew older and developed myopia. In controls, the PhNR was dependent on bipolar cell input. However, this relationship was absent in myopic marmosets. Aim 4 using SD-OCT assessed the effect of myopic growth on choroidal morphology: thickness, area, luminal area, stromal area, vascularity index and luminal/stromal area ratio. All measures were significantly lower in treated marmosets compared to controls and decreased with increasing degree of myopic growth. Aim 5 evaluated the interrelationship between the gross anatomical, cellular and functional effects of myopia on the retina and choroid described in the previous aims. The ppRNFL was thinner in myopic eyes and changed as a function of eye growth. The inner retinal anatomical changes did not affect inner retinal function. Choroidal parameters were significantly associated with the a- and d-wave amplitudes. In summary, this thesis provides evidence of the effect of myopia development and progression on the inner retina and choroid of marmosets. All these changes were associated with myopic elongation. The early attenuation of retinal responses might reflect retinal signal processing mechanisms in response to hyperopic defocus. The choroidal changes confirmed in myopic marmosets were associated with reduced photoreceptor function, which reflects compromised metabolic support to the outer retina. This thesis confirms the effect of myopic growth on the retinal and choroidal structure and describe early biomarkers of altered anatomical changes that will help understand the reduced visual performance of myopic eyes and increased risk of developing secondary myopic complications.
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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)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.
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Neural Mechanisms of Luminance PerceptionVisual 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 BrainThere 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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Effects of Mild Traumatic Brain Injury (mTBI) on Retinal Structure, Function, and Pupillary Light ResponsesPurpose: 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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Color Transparency: Geometry, Motion, Color, Scission, and InductionObjects 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 GlaucomaGlaucoma 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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Mild Traumatic Brain Injury (mTBI) and Photosensitivity: Objective Pupillometric FindingsBackground 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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Objective assessment of visual dysfunction in the acquired brain injury (ABI) population using the visual-evoked potential (VEP)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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Oculomotor rehabilitation for reading dysfunction in mild traumatic brain injuryAbstract: 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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Roles of Calcium Signaling and Protein Kinase C Activation in Mediating Receptor Control of Corneal Epithelial RenewalEpidermal growth factor, EGF, is one of the essential growth factors that stimulates injury-induced corneal epithelial healing rates. Cell signaling contributors mediating this response include capacitative calcium entry (CCE) activation and protein kinase C (PKC) isoform stimulation. This study shows in human corneal epithelial cells, HCEC, that CCE is preferentially activated by the PKC isoforms and . Moreover such activation requires increases in plasma membrane Ca2+ influx through store-operated channels. Therefore, EGF-induced stimulation of cell proliferation and migration may depend on unique effects mediated by six different PKC isoforms identified in HCEC. TRPV1 is a vanilloid subtype of the transient receptor potential protein superfamily. This isoform is a subunit of a non-selective cation channel mediating downstream responses to heat, low pH, or noxious stimuli. TRPV1 expression has been recently described in some epithelial tissues and induces proinflammatory cytokine release through mitogen-activated protein kinase (MAPK) superfamily stimulation. This study describes in HCEC the signaling pathways mediating TRPV1-induced increases in proinflammatory cytokine release. It suggests that epithelial TRPV1 receptor activation by noxious stimuli contributes in-vivo to mounting proinflammatory reactions.
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Electronic Text Displays: Reading Rehabilitation of Low Vision Patients with Age-Related Macular DegenerationThe purpose of this study was to investigate whether reading performance, measured in words per minute, improved during an hour of within-session practice. The reading methods were three computer-generated presentations including (1) MNREAD, a modified page format, (2) RSVP, which presents one word at a time, and (3) SCROLL, where text pans from right to left across a screen. Forty-five young readers with normal vision, forty-five elder readers with normal vision, and forty-five readers with low vision due to age-related macular degeneration read by one of these methods. None of the participants had previous experience reading with MNREAD, RSVP of SCROLL. There was little evidence that within-session practice improved performance. Only 10 of 135 participants had modest reading rate gains, and there was no statistical difference between reading method or subject group for this small subset of readers.