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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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  A Theory of Cortical Map Formation in the Visual Brain

  Najafian, Sohrab (2022-12)

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

  Chen, Tiffany Ying-Hsuan (2022-12)

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

  Toan, Trinh (2023-08-01)

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

  Ribolla, Sofia (2022)

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

  Guo, Crystal (2022-06-13)

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

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

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

  Saksena, Sanjana (2022-04-20)

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

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

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

  Huang, Zhehao (2024-03-30)

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

  Joshi, Nabin (2017-09-25)

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

  Roy, Kaushambi (2017-08)

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

  Gong, Celia (2017)

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

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