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  Helping Our Graduate Students SOAR: Promoting Scholarship and Populating Our Institutional Repository

  Wells, Elaine (East Tennessee State University Charles C. Sherrod Library, 2024-11-18)

  The author describes how a requirement that our graduate students deposit theses and dissertations into our institutional repository (SOAR) helped to build our online scholarship, educate and strengthen graduate stu- dents’ identities as scholars, and forge relationships with the library. Taking advantage of the synergy brought about by a new open access policy, a robust digital repository, and library staff committed to advancing accessible scholarly works, we developed ways to educate, encourage, and promote our newest scholars. Based upon our success thus far, we will develop workshops and tutorials that will be extended to junior faculty to advance their scholarly success.
• Functional contributions of ON and OFF pathways to human vision

  Poudel, Sabina (2024)

  "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

  Maruya, Akihito (2024)

  "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

  Lin, Carol (2024-08)

  "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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  Digital eye strain and pupillary response to blue light

  Ng, Derek (2024)

  "Purpose: Digital eye strain (DES), a multifactorial condition affecting millions worldwide, often implicates blue light as a contributing factor. While blue light blocking filters are marketed to alleviate DES symptoms, evidence supporting their efficacy remains limited. Intrinsically photosensitive retinal ganglion cells (ipRGCs), exhibiting peak sensitivity to blue light, are involved in regulating pupil constriction and circadian rhythms. Notably, blue light elicits varying ipRGC-mediated pupil responses between individuals. This study investigated a potential association between self-reported DES symptoms and individuals' ipRGC-mediated pupil responses. Method: Twenty-five visually normal subjects, 18-30 years of age, participated in the experiment. They began by reading random words on a tablet computer for 20 minutes. Before and after the reading task, participants completed a symptom survey to assess DES severity. Subsequently, they were exposed to a blue background light of varying intensities within the dome of a pupilometer. The pupil light reflex was recorded for each intensity and analyzed. Results: The pupil diameter's EC50 value in response to blue light exhibited a statistically significant correlation with the total symptom score (p=0.0003), extrinsic symptom score (p=0.006) and intrinsic symptom score (p=0.0003). Similarly, the LogEC50 value also demonstrated a statistically significant correlation with total symptom score (p=0.002), extrinsic symptom score (p=0.02), and intrinsic symptom score (p=0.001). Conclusion: Subjects with greater DES scores exhibited reduced sensitivity when adapting to blue light, indicating a potential link between ipRGC function and DES symptoms. "
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  Upregulation of Gap Junction Connexins in Glaucoma

  Fareed, Nada (2024)

  Glaucoma is a leading cause of irreversible blindness, which is characterized by a progressive degeneration of the optic nerve and loss of retinal ganglion cells (RGCs). Glaucoma currently affects 3.5% of individuals aged 40 to 80 years, and the incidence of glaucoma is increasing together with life expectancies (Wagner et al., 2022). There is strong evidence that intercellular communication via gap junctions (GJs) facilitates secondary cell death, by means of the so-called “bystander effect” is which dying cells releases toxins that lead to the death of neighboring cells to which they are coupled (Akopian et al., 2014; 2017). Pharmacological blockade of GJs or genetic deletion of GJ subunit connexins Cx36 (Akopian et al., 2017) or Cx43 (Batsuuri et al., 2023) showed an increase in neuronal survivability by greater than 70% in glaucomatous retinas providing clear evidence that GJs can mediate secondary cell death, which can account for loss of most retinal neurons. Since Cx36 is expressed by GJs between retinal neurons and Cx43 is expressed between glial astrocytes, there are potentially two separate pathways that may underlie cell loss in glaucoma. This raises the important question of whether these pathways are independent mechanisms for cell death or are interdependent. Interestingly, both Cx36 and Cx43 are upregulated in glaucomatous retinas (Akopian et al., 2017; Batsuuri et al., 2023). Therefore, to assay the interdependence of bystander death mediated by Cx36- and Cx43-expressing GJs in glaucoma, we determined if their upregulation were interconnected. Understanding the potential interdependence of these two GJ-mediated bystander cell death pathways would help define potential targets for neuroprotection in glaucoma.
• Diurnal Variations in Scotopic and Photopic Flash Electroretinogram

  Wang, Jesse (2024)

  "Purpose: To determine the pattern of the diurnal variations in retinal responses measured with the full-field scotopic and photopic electroretinogram (ERG). Methods: Full-field flash ERGs were recorded with DTL electrodes after pupil dilation from 6 normal healthy subjects at 3AM, 9AM, 3PM and 9PM (one subject at 6AM, 12PM, 6PM, 12AM) on four separate days using a desktop ganzfeld ERG recording system (Diagnosys LLC). The test scotopic ERG test protocol consisted of 40 minutes of dark-adaptation followed by recordings with brief (<4ms) blue (440nm) test flashes in the range of 1x10-6 to 20 scot cd.s/m2. The photopic ERG test protocol consisted of 15 minutes of light-adaptation to 8 scot cd/m2 blue background followed recordings with brief red (690nm) test flashes in the range of 6x10-2 to 6.4 phot cd.s/m2 on the adapting background. The Scotopic Threshold Response (STR), scotopic and photopic b-waves and the Photopic Negative Response (PhNR) amplitudes were plotted as a function of test flash intensity and fit with the Naka-Rushton equation to extract the saturated amplitude (Vmax), slope (n) and semisaturation constant (K) parameters for each ERG measures. The fit parameters were plotted as a function of the time of the day when the recordings were performed to examine their diurnal variation. Saliva samples were collected and salivary melatonin was assayed (Salimetrics LLC) at 8 different time points during the day from each subject on one separate occasion and prior, during and after each ERG session. Results: The Vmax of the ERG measures demonstrated statistically significant systematic diurnal variation. The Vmax of the Scotopic b-wave and the STR did not change appreciably from 3AM to 9AM but thereafter gradually increased to reach a maximum value at 9PM. The difference in the mean value of the Vmax between the 3AM and 9PM recordings was statistically significant for the scotopic b-wave (173uv and 338uv, p=0.0013) and the STR (15uv and 22uv, p=0.03). with the halfway point for this amplitude increase being 11AM. The Vmax of the photopic b-wave and PhNR showed a steep increase from 3AM to 9AM and thereafter a more gradual increase at 3PM to slightly reduce again by 9PM. The difference in the mean value of the Vmax between the 3AM and 3PM recordings was statistically significant for the photopic b-wave (60uv and 92uv, p=0.04) and the PhNR (36uv and 61uv, p=0.019) with the halfway point for this amplitude increase being 6AM. Salivary metalonin concentration on average started to show an increase around 9AM from daytime baseline value of 1 pg/ml to a peak of 16 pg/ml around 3AM and then reduced to 4 pg/ml by 9AM. Conclusions: The maximal amplitude of the scotopic ERG parameters are achieved later during the day compared to the photopic ERG parameters that achieve maximal amplitudes at earlier times. The saturated amplitude of scotopic and photopic ERG measures have their lowest values around 3AM when salivary melatonin concentration is maximal. The relationship between the diurnal rhythms of melatonin and retinal function as measured by the ERG warrants further investigation. "
• Retinal Ganglion Cell Function in Diabetes Mellitus

  Vasiu, Sakshi (2024)

  "Purpose: To evaluate retinal ganglion cell function in diabetic patients with no retinopathy. Methods: The full-field photopic flash electroretinogram (ERG) was recorded from 11 diabetics patients (55.75 ± 14.77) and 11 age-matched controls (50.17 ± 15.18) with a ColorBurst TM handheld stimulator (Diagnosys LLC). The visual stimuli consisted of 40 ms duration red (640 nm) test stimuli of strengths ranging from 0.25 cd/m2 to 1500 cd/m2 delivered on and constant rod-saturating blue (470 nm) background of 7cd/m2. The Intensity response function of the PhNR and the b-wave amplitudes plotted as a function of stimulus strength were fitted with a generalized Naka-Rushton equation of the form V(I)/Vmax = In /(In +Kn ) and the fit parameters of K, n and Vmax were compared between the diabetic patients and control subjects. Visual field sensitivity was measured by behavioral perimetry using the Humphrey Visual Field Analyzer 10-2 and 24-2 SITA-standard tests. Structural parameters of the retina, namely area of the foveal avascular zone (FAZ), superficial vascular plexus density (SVD), deep vascular plexus density (DVD)and Retinal Nerve Fiber Layer (RNFL) thickness were measured with the Heidelberg OCTA. Linear regression analysis was used to study the correlation between affected ERG fit parameters and aspects of visual field sensitivity and retinal structural parameters. Results: The mean ages were not significantly different between the diabetic patients and control subjects. The average value of the PhNR semi-saturation constant for the diabetic patients and control subjects were 83.64+39.96 and 32.21+20 and the difference was statistically significant (p=0.0054). The average value of the PhNR slope for the diabetic patients and control subjects were 0.83+0.19 and 1.39+0.17 and the difference was statistically significant (p=0.0000018). PhNR Vmax was not statistically significantly different between the diabetic patients (30+7.12) and controls (30.18+6.45). The parameters of the Naka-Rushton fits to the b-wave responses were not significantly different between the two groups. A positive correlation was seen between the semi-saturation constant of the PhNR in diabetics and self-reported HbA1c% (r=0.72, m=22.8, p=0.029) and a negative correlation was observed between the semi-saturation constant of the PhNR and 10-2 mean sensitivity (r=0.67, m=-0.03, p=0.02). A positive correlation between the semi-saturation constant and SVD (r=0.66) and DVD (r=0.67) were seen in control subjects, whereas negative correlation was seen in diabetics eyes (r=0.5 and r=0.4). Conclusion: Retinal ganglion cell sensitivity is compromised in diabetic patients with no retinopathy as indicated by an increase in the value of the full-field PhNR semi-saturation constant while responses of their input neurons, namely bipolar cells, as reflected by the b-waves is relatively normal. Compromise of retinal ganglion cell function may underlie the earliest visual sensitivity changes diabetic patients. Further longitudinal studies are warranted to determine whether changes in ganglion cell function precedes changes in superficial and deep vessel density. "
• Development of a Pediatric Digital Eye Strain Questionnaire

  Aguilar, Stephanie (2024)

  "Objectives: The aim of the present study was to create a valid and reliable method of determining to what extent children experience symptoms of digital eye strain (DES). Methods: The initial version of the pediatric digital eye strain questionnaire was developed using a literature review, consultation with experts and a pretest performed on 6-8-year-olds. A pilot test using a revised version of the questionnaire was performed on 70 6-12-year-old participants. Content validity was established by discussion with an expert. Construct validity was evaluated by performance of the pediatric DES questionnaire and the Computer Vision Syndrome Questionnaire (CVS-Q) by optometry students. Test-retest repeatability was tested using Bland Altman analysis and a significant cutoff score was established using the linear regression equation to determine the value equivalent to the previously assigned cutoff for the CVS-Q of 6. Results: The questionnaire evaluated 12 DES symptoms’ frequency in a simple, self-administrable method. The mean total score of the pilot test was 7. 45% of the participants in the pilot test had a significant score for DES. The questionnaire had excellent test-retest repeatability and construct validity r=0.81 (p<0.001). No significant correlation was found between the reported total number of hours of screen time per week and the total symptom score (r = 0.30, p = 0.47). Conclusions: This study indicates that almost half of children may be experiencing adverse ocular symptoms associated with screen use. The questionnaire provides a valid and reliable method for identification of DES symptoms in children ages 6-12 years. Optometrists, pediatricians and parents alike may find use for this questionnaire to evaluate for digital eye strain in children. "
• The Role of Astroglial Connexin43 in Experimental Glaucoma.

  Batsuuri, Khulan (2023-08)

  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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  Cognitive Demand, Concurrent Viewing Distance, and Digital Eye Strain

  Sharvit, Elianna (2023-08)

  Purpose: Digital devices are now ubiquitous in modern daily life. Reports of digital eye strain (DES) symptoms are occurring frequently, particularly since the recent COVID-19 pandemic. Despite its prevalence, the mechanisms underlying DES have not been fully elucidated and there is currently no clinically proven treatment. Given that both mental effort and the accommodative and vergence demand have been associated with DES, the purpose of this study was to evaluate the relationship between the cognitive demand of the task, mode of presentation, working distance and symptoms of DES. Method: The study was performed on 30 young, normally-sighted individuals. Each participant completed four trials, each of which included a 30-minute reading task. The four conditions entailed: (1) a cognitively demanding task performed on a digital device (tablet) and (2) a less cognitively demanding task performed on the same digital device. Trials (3) and (4) were identical to (1) and (2) except that the tasks were performed on printed paper. Both prior to and immediately following each 30-minute task, subjects completed a 10 question DES symptom survey. For all four conditions, subjects wore a Clouclip, a spectacle-mounted device which uses infrared technology to monitor the working distance objectively every 5 seconds. Results: While all four 30-minute reading tasks induced symptoms of DES, the increase in symptoms was greater for the cognitively demanding tasks (p= <0.0001). However, there was no significant difference in symptoms between performing the tasks on paper versus the tablet computer (p=0.83). With regard to working distance, there was no difference between the four testing conditions (p=0.11). However, all tasks showed a similar significant reduction in working distance (p=0.001), on average from 32 to 30cm, over the first ten minutes of the task, with the working distance remaining relatively stable after this initial period. Conclusion: These results suggest that cognitive demand plays a greater role in DES than the mode of presentation. In addition, we found no evidence that working distance varies with cognitive demand or the method of presentation. However, it did decrease during the first 10 minutes of each trial. Further work is needed to explain the role of cognitive demand in DES.
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  A Tale of Two Tools: Comparing LibKey Discovery to Quicklinks in Primo VE

  Locascio, Jill; Rubel, Dejah (Core: Leadership, Infrastructure, Futures, a division of the American Library Association, 2023-06-19)

  Consistent delivery of full-text content has been a challenge for libraries since the development of online databases. Library systems have attempted to meet this challenge, but link resolvers and early direct linking tools often fell short of patron expectations. In the last several years, a new generation of direct linking tools has appeared, two of which will be discussed in this article: Third Iron’s LibKey Discovery and Quicklinks by Ex Libris, a Clarivate company. Figure 1 shows the “Download PDF” link added by LibKey. Figure 2 shows the “Get PDF” link provided by Quicklinks. The way we configured our discovery interface, a resource cannot receive both the LibKey and Quicklinks PDF links. These two direct linking tools were chosen because they were both relatively new to the market in April 2021 when this analysis took place and they can both be integrated into Primo VE, the library discovery system of choice at the authors’ home institutions of SUNY College of Optometry and Ferris State University. Through analysis of the frequency of direct links, link success rate, and number of clicks, this study may help determine which product is most likely to meet your patrons’ needs.
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  Alterations to the structure and function of the retina and choroid in an experimental model of progressive myopia

  Ablordeppey, Reynolds (2023-06)

  Myopia 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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  Effects of Test Flash Duration on the Photopic Negative Response (PhNR) of the Flash Electroretinogram

  Garmsiri, Behrad (2023-06)

  Purpose: The Photopic Negative Response (PhNR) of the cone mediated electroretinogram (ERG) is a slow potential with negative polarity that appears after the b-wave. The PhNR originates from the electrical activity of retinal ganglion cells (RGCS) and has clinical utility. The PhNR is typically recorded to a brief (<4ms) test flash, we explored the effect of increasing the stimulus duration on the PhNR amplitude of normal subjects in an ongoing attempt to optimize the stimulus conditions for its clinical use. Methods: ERGs were recorded with DTL electrodes from normal subjects (N=10) in the age range 23-53 years using the ColorBurst handheld ganzfeld stimulator and hardware from Diagnosys (Lowell, MA). The stimuli consisted of red test flashes on constant blue background (8 phot cd.s/m.sq). The test flashes were either brief stimuli (<4 ms duration) in the range of 0.00625 - 6.4 phot cd.s/m.sq or longer duration (20-80 ms) in the range of 0.125-1500 cd/m.sq. A new algorithm in the Espion software with objective sweep selection based on various noise and artifact identification criteria was used to average repeated responses at each test flash intensity. The PhNR amplitude of the averaged waveform was plotted as a function of test flash intensity and fitted with the standard Naka-Rushton equation. The saturated amplitude (Vmax), slope (n) and semisaturation constant (K) derived from the fits were analyzed. The student t-test was performed to compare the fit parameters across different test flash durations with correction for multiple comparisons using the Holm’s method. Results: Vmax for the brief stimulus was 20+7 microvolts and increased to 23+2 microvolts for 20 ms duration stimuli. With further increase in stimulus duration the PhNR Vmax was 34+8 v, 42+10 v and 37+10 v for 40 ms, 50 ms and 60ms duration stimuli and thereafter reduced to 29+7 v for an 80 ms stimulus duration. The Vmax amplitude differences between the brief and longer duration stimuli were statistically significant only for the 40 ms (p=0.04), 50 ms (p=0.001) and 60 ms (p=0.01) after correcting for multiple comparisons. Responses to stimulus durations up to 60 ms demonstrated a single PhNR trough and for longer duration stimuli two PhNR troughs were observed one following light onset after the b-wave and another following light offset. Conclusions: The saturated PhNR amplitude is larger for longer duration stimuli and is maximal in the range of 40-80 ms duration. The larger PhNR amplitude at the intermediate test flashes likely reflect the summation of the PhNR to stimulus onset and offset and could potentially have more value in assessing retinal ganglion cell function in patients with disease affecting the optic nerve and/or inner-retinal neurons.
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  Accommodation over Time in Children Wearing Multifocal Soft Contact Lenses for Myopia Control

  Zlatin, Zachary (2023-05)

  Introduction The prevalence of myopia and its ocular complications increases each year worldwide and the complications of myopia are predicted to become the leading cause of blindness by 2050 (Holden Ophthamology 2016). Common therapies for myopia management include low-dose atropine, bifocals or Progressive Addition Lenses (PALs), orthokeratology (OK), and multifocal contact lenses (MFCL). One potential mechanism for OK and MFCLs to reduce myopia progression is by imposing peripheral myopic defocus on the retina. MFCL wear can reduce accommodation compared with single vision contact lenses (SVCL), potentially reducing peripheral myopic defocus and causing variable efficacies of MFCLs (Gong OVS 2017). The change in accommodation with MFCL use varies between MFCL designs. Auditory biofeedback training can decrease the accommodative lag during MFCL wear in young adults (Wagner Sci Rep 2020). We assessed: Differences in accommodative lag between children using low-dose atropine, OK, and MFCLs compared to a single vision spectacle control. Differences in accommodation between different MFCL designs. Differences in accommodation between viewing through SVCLs and MFCLs. The effect of biofeedback training on accommodation in children during MFCL wear. Methods Myopic children habitually using low-dose atropine, OK, or MFCLs as well as myopic children not undergoing myopia management (spectacle control) (19 male/ 24 female) were recruited from the Pediatric and Myopia Management Clinics at the University Eye Center, SUNY College of Optometry. Low dose atropine (n = 11), OK (n = 5), and spectacle control (n = 11) subjects’ accommodative lag was measured using an infrared (IR) photorefractor, using a stimulus at 0, 2.5, 3, and 4D. For the MFCL subjects (n = 17), accommodation through SVCLs and their habitual MFCLs before, after, and 1 week following biofeedback training were measured identically to the other subjects at the same distances. Differences in accommodative lag were measured using mixed effects multiple linear regression adjusting for accommodative stimuli. Results There was no significant difference between accommodation in the low-dose atropine (p = 0.8), OK (p = 0.3), and MFCL (p = 0.3) groups compared to the spectacle control. Eyes wearing MFCLs exhibited significantly increased lag of accommodation compared with SVCLs prior to the biofeedback training (SV vs. MFCL, p < 0.05). Specifically, eyes viewing through Biofinity MFCLs showed a significantly greater lag than MiSight (p < 0.05). Biofeedback training showed a tendency to decrease lag immediately following biofeedback training (p = 0.2) and significantly decreased lag 1 week later (p < 0.01). Both immediately and one week later, subjects that showed lower pretreatment accommodation had significantly greater decreases in lag following biofeedback training (p < 0.05). Conclusions Our findings show that pediatric subjects wearing MFCLs for myopia management show an increased accommodative lag compared to wearing SVCLs. The lag of accommodation while viewing with MFCLs differs between MFCL designs. Biofeedback training can significantly decrease lag in children during MFCL wear one week later, similar to previous findings (Wagner Sci Rep 2020). Subjects who displayed the greatest accommodative lag prior to the train showed the biggest improvements in accommodation before the biofeedback training, suggesting individuals with low accommodation while viewing through MFCLs use may yield the greatest benefit from biofeedback training. Biofeedback training may be effective in increasing the amount of peripheral myopic defocus during MFCL wear and thus increase the efficacy of MFCL wear for myopia management in children.
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  Regional Differences in the Relationship Between Retinal Structure and ON-OFF Pathway Function in Myopic Patients

  Dellostritto, Stephen (2023-05)

  Purpose: The purpose of this study was to measure the effect of myopia on ON and OFF pathway asymmetries displayed between 5˚ to 30˚ of eccentricity and examine the structure-function relationship between retinal thickness and visibility of light and dark stimuli in eccentric quadrants of myopic eyes. Methods: Eighteen eyes were randomly selected from human subjects and all myopic subjects underwent testing with habitual soft contact lens correction. Subjects underwent ON-OFF perimetric testing in the test eye. The complete procedure is referenced and discussed in the body of the manuscript. Stimuli were presented at various contrasts across 30-degrees of the visual field and stimuli increased in size as a function of eccentricity. Structural and functional testing, including ultra-wide field macular optical coherence tomography (OCT), 30-2 static automated perimetry (SAP) mean sensitivity, peripheral autorefractive (AR) measurements, and axial length (AL), were also measured. All testing, except axial length measurements, were taken with subjects fully corrected in soft contact lenses. Results: There was a statistically significant positive correlation between AL and combined light and dark errors across the entire testing area of 5-30° (p=0.0019) as well as each eccentric range (5-10° p=0.0389; 11-20° p=0.0015; 21-30° p =0.0008). There was a statistically significant positive correlation between errors to light stimuli as a function of AL across the entire testing area of 5-30° (p=0.0251), 11-20° (p=0.0207) and 21-30° (p =0.0178). There was a statistically significant positive correlation between AL and dark stimuli errors across the entire testing area of 5-30° (p=0.0461), 11-20° (p=0.0424) and 21-30° (p =0.024). There was no statistically significant correlation when analyzing errors to light and dark stimuli separately at the 5-10° eccentricity. There was a statistically significant negative correlation between RE and combined light and dark errors across the entire testing area of 5-30° (p=0.0444) and a statistically significant negative correlation at the most peripheral eccentric range of 21-30° (p=0.0128). Subjects displayed higher errors to light stimuli over the entire testing area 5-30° (p=0.0166) and 21-30° (p=0.0007), but not at 5-10° or 11-20° (5-10° p=0.7043; 11-20° p=0.2572). The quadrant with the greatest average retinal thickness (IT) was associated with the lowest %errors (6.45 ± 6.56) and highest visual field mean sensitivity (VFMS, 30.9 ± 1.08 dB), whereas the quadrant with the least average retinal thickness (SN) was associated with the highest % errors (22.77 ± 15.93, p=8.91 x 10-9 for IT vs SN comparison) and among the lowest MS (29.43 ± 1.34, p=0.0020 for IT vs SN comparison). Conclusion: Higher levels of myopia are associated with greater response errors during ON-OFF perimetric testing, with higher error rates in response to light targets compared to dark targets. Both findings are most pronounced at the 21–30-degree eccentricity and have a stronger correlation with axial length compared to refractive error. Higher rates of error on ON-OFF perimetry correspond to thinner retinal thickness in the corresponding retinal quadrant. The highest average percent errors on ON-OFF perimetric testing were present in the superonasal visual field, which coincides with the thinnest total retinal thickness in the corresponding region of the retina (interotemporal). Better understanding of the structural and correspond to thinner retinal thickness in the corresponding retinal quadrant. The highest average percent errors on ON-OFF perimetric testing were present in the superonasal visual field, which coincides with the thinnest total retinal thickness in the corresponding region of the retina (interotemporal). Better understanding of the structural and corresponding functioning relationship between ON-OFF perimetric testing and retinal thickness may enhance our understanding of myopic refractive development.
• Effects of Scheduled Breaks on Digital Eye Strain and the 20-20-20 Rule

  Johnson, Sophia (2023-05)

  Purpose: The use of digital devices has increased substantially over the past two decades across all age groups, particularly during the recent pandemic, for both vocational and avocational purposes. Digital eye strain (DES) involves a range of visual and ocular symptoms that can be categorized into oculomotor/refractive abnormalities or dry eye symptoms. The so-called 20-20-20 rule, whereby individuals are advised to fixate an object at least 20 feet (6m) away for at least 20 seconds every 20 minutes is widely cited as a method for minimizing symptoms. Unfortunately, there is little or no peer-reviewed evidence to support this so-called rule. Accordingly, the aim of the present investigation was to determine whether 20-second breaks are indeed effective in reducing the adverse effects of digital device usage, and if so, then to identify the specific schedule that has the greatest success in controlling symptoms. Methods: The study was performed on 30 young, visually-normal subjects who performed a highly demanding 40-minute reading task from a tablet computer. The task required them to read random words and to identify which began with a specific letter chosen at random by the experimenter. The task was undertaken on four separate occasions, with 20-second breaks being allowed every 5, 10, 20 or 40 minutes (i.e., no break), respectively. Both before and immediately after each trial, subjects completed a questionnaire regarding ocular and visual symptoms experienced during the session. Additionally, both reading speed and task accuracy was quantified during the trial. Results: A significant increase in post-task symptoms (with respective to the pre-task value) was observed for all four trials (p<0.001). However, there was no significant effect of scheduled breaks on reported symptoms (p=0.70), reading speed (p=0.93) or task accuracy (p=0.55). Conclusions: While widely cited as a treatment option, these results do not support the proposal of using the 20-20-20 rule as a therapeutic intervention for DES. Future studies should look at alternative break schedules to determine their efficacy.
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  Effects of Gingko biloba on Systemic and Retinal Blood Circulation

  Lin, Durpri (2023-05)

  Introduction: The use of alternative medicine has increased in recent years due to its minimal side effects and holistic approach to healthcare. Ginkgo biloba extract (GBE) is a natural antioxidant derived from leaves of the Maidenhair tree and is known to improve blood vessel health. However, its effect on the retinal circulation is not fully understood. The purpose of this study is to examine the effect of GBE oral supplements on the retinal circulation. Methods: Blood pressure (Omron HEM-705CP), intraocular pressure (Canon T2 non-contact Tonometer), and blood flow velocities in the ophthalmic artery, central retinal artery, and short posterior ciliary arteries (Color Doppler imaging, Sequoia) were obtained from participants aged 22 to 36 with good ocular and systemic health. Measurements were performed between 12-5pm to control for circadian rhythm effects at 3 study visits: 1 week before baseline at pre-supplement visit (T-1), at baseline (T0) and after 4 weeks of 240mg/day GBE supplementation at post-supplement visit (T4). Ocular perfusion pressure (OPP) was calculated as OPP = 2/3 * (Mean Arterial Pressure – IOP). Results: Thirteen participants were recruited (5m, 8f; 25.54 ± 3.64 years). No significant changes in systemic blood pressure, OPP or retinal circulation were observed between pre-supplement visit (T-1) and baseline (T0) prior to GBE supplementation. However, the ophthalmic and short posterior ciliary arteries peak systolic velocities increased from baseline (T0) to post-treatment (T4) (ophthalmic artery baseline ave ± SD: 18.97 ± 6.67cm/s; post-treatment:24.33 ± 6.90cm/s; short posterior ciliary artery baseline: 10.56 ± 1.87cm/s; post-treatment: 11.58 ± 1.97cm/s; both p < 0.05). The increases in ophthalmic and short posterior ciliary arteries peak systolic velocities did not correlate with changes in systolic BP, diastolic BP, or OPP. Discussion: Our preliminary data suggests that 240mg/day of Ginkgo biloba extract (GBE) may increase blood flow in two major retinal ocular arteries. Such increase appears independent from changes in systemic blood pressure or OPP.
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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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