"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."

"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."

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.

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

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

Purpose: Longitudinal chromatic aberration (LCA) provides a cue to accommodation with small pupils. However, large pupils increase monochromatic aberrations, which may obscure chromatic blur (McLellan, Marcos, Prieto, & Burns, 2002). We examined the effect of pupil size and LCA on accommodation in color normal and deutan observers. Methods: Participants were nine normal trichromats, three deuteranomalous trichromats, and two deuteranopic dichromats (anomaloscope and D-15). Accommodation was recorded by infrared optometer (100 Hz) and pupil by video-camera (30 frames/s) while observers viewed a sinusoidally moving Maltese cross target (1-3 D at .2 Hz) in a Badal stimulus system. There were two illumination conditions: white (3000 K; 20 cd/m2) and monochromatic (550 nm with 10 nm bandwidth; 20 cd/m2) and two artificial pupil conditions (3 mm and 5.7 mm). Separately, static measurements of wavefront aberration were made with the eye accommodating to targets between zero and 4 D (COAS, Wavefront Sciences). Results: Dynamic gain to vergence modulation increased significantly with pupil size in monochromatic (p=.005) but not white light (p=.12), and gain increased significantly with addition of LCA at both pupil sizes (5.7 mm, p=.004; 3 mm, p=.02). Mean RMS higher order aberration increased from .23 m with small pupils (3 mm) to .48 m with large pupils (5.7 mm). There were no significant differences in dynamic accommodation between color normal and deutan individuals for any condition (.68≤p≤.96). Normals and deutan observers showed large individual differences in dynamic gain to both vergence and LCA. Mean responses also varied among individuals, but deuteranomalous observers over-accommodated compared to color normal observers (.06≤p≤.12). Conclusions: Large individual differences in accommodation to wavefront vergence and to LCA are a hallmark of accommodation in normal and deutan observers. LCA continues to provide a signal at large pupil sizes despite higher levels of monochromatic aberrations. Monochromatic aberrations may defend against chromatic blur at high spatial frequencies, but accommodation responds best at 3 c/deg where blur from higher order aberrations is less (Mathews, 1998; Mathews & Kruger, 1994).

Primary Objective: To determine whether critical flicker frequency (CFF) thresholds are elevated in individuals with traumatic brain injury (TBI) and correlated with the degree of motion and light sensitivity. Methods and procedures: The foveal CFF threshold was assessed in individuals with TBI (n=18) having varying degrees of light and motion sensitivity. Mean CFF values were obtained using the ascending and descending psychophysical method of limits with binocular viewing at 40 cm. A rating-scale questionnaire was used to assess the degree of light sensitivity and motion sensitivity. These parameters were also assessed in a visually-normal cohort. Main outcomes and results: CFF in the TBI group was not significantly different across age groups from the visually- normal cohort. However, mean CFF among the TBI subjects was significantly higher for the “light sensitive” and “motion sensitive” subgroups when compared to the “not light sensitive” and “not motion sensitive” subgroups. The majority of TBI subjects had both light and motion sensitivity. Conclusion: An elevated CFF among a subgroup of TBI subjects may be related to the symptoms of light and motion sensitivity that many TBI patients experience. Underlying mechanisms involving disinhibition of the magnocellular pathway as a result of brain injury may be causal of the hypersensitivity to light and motion. CFF thresholds can potentially aid clinicians in determining methods of treatment for TBI patients.

PURPOSE: To design a contrast sensitivity perimetry test with the potential to improve clinical management of glaucoma by decreasing test-retest variability in defective areas while maintaining good sensitivity to glaucomatous loss. METHODS: Twenty patients with glaucoma, ten age-similar control subjects and ten young control subjects were recruited. One eye was tested per subject. All subjects were tested with contrast sensitivity perimetry (CSP), and conventional automated perimetry (CAP). Stimuli for CSP were Gabor patches with a peak spatial frequency of 0.375 cpd and a two-dimensional spatial Gaussian envelope with the most of the energy concentrated within a central circular region 4 degrees in diameter. For CSP, stimuli were presented at 26 locations over the central visual field, excluding the central 5 degrees and with the emphasis on the nasal hemifield. Neuroretinal rim area of the patients was measured using retinal tomography (HRT II). Young subjects were tested on CSP using 4-reversal and 8-reversal staircases to estimate variability and test duration. Bland-Altman analysis of agreement was used to assess test-retest variability, to compare depth of defect for the two perimetric tests, and to investigate the relation between contrast sensitivity and neuroretinal rim area. RESULTS: With 4-reversal staircases, for both Size III stimuli and Gabor stimuli, variability increased as sensitivity decreased (r2 > 5%, p<0.001), but at a shallower rate for the Gabor stimuli (Z > 2.9, p<0.005). With 6- and 8- reversal staircases, the correlation between sensitivity and variability was not significant (r2 = 0.05%, p>0.5) and the slope of the regression line was shallower than for the 4-reversal staircases (Z>2.4, p< 0.01). Depth of defect was on average similar for the two devices, but for some patients the size III stimuli tended to yield deeper defects than Gabors in regions of lower sensitivity. The relation between rim area and perimetric sensitivity was more consistent for contrast sensitivity perimetry than for conventional perimetry (Z=9.3, p < 0.0005). For control subjects there was a significantly shallower decline in sensitivity with eccentricity using Gabor stimuli than with conventional size III stimuli (Z=3.78, p<0.0005), and overall test-retest variability was similar for staircases with 4 to 8 reversals. CONCLUSION: Contrast sensitivity perimetry demonstrated reasonably low test-retest variability and good ability to detect defect. It also showed a structure-function relation that was independent of the degree of glaucomatous loss. Further research on contrast sensitivity perimetry is needed to evaluate its utility in monitoring progression of glaucoma and effects of treatment.