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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. "
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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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