• Development & Evaluation of a Contrast Sensitivity Perimetry Test for Patients with Glaucoma

      Hot, Aliya (2007-05-29)
      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.
    • Evaluating Equiluminant Chromatic Stimuli as Stimuli for Assessing Glaucomatous Damage

      Ly-Schroeder, Emily (2008-01-10)
      Purpose: To examine the potential clinical utility of equiluminant chromatic stimuli for assessing glaucomatous damage. Pan et al. (2006) found that equiluminant red-green chromatic stimuli could have good ability to detect defects as well as low test-retest variability, but clinical utility was limited due to the small dynamic ranges for their stimuli. The current study increased the dynamic range by using larger stimuli and including tritan stimuli. Methods: Luminance, red-green (R-G), and tritan stimuli were created by modulating a large square (3 degrees per side) from an equal energy white (20 cd/m2) along three cardinal directions in color space. Contrast sensitivity was measured at four locations with an eccentricity of 12 deg. along the 45, 135, 225, and 315 degree meridia. Twenty-five patients with glaucoma and twenty-six control subjects free of eye disease were tested monocularly at two separate sessions within a two-week time period. Sensitivities were reported in decibel (dB) units, where 1 dB=-1 (log contrast threshold) x 10. Results: The dynamic ranges were 11 and 13 dB for the tritan and red-green stimuli. Test-retest variability was dependent on depth of defect for the two chromatic stimuli (r>0.2, p<0.25) but not for the achromatic stimuli (r=0.01, p=0.46). Matched t-tests found that, on average, defect depths were similar for the red-green and luminance stimuli (t=0.5, p=0.30), and were slightly deeper for the luminance stimulus than for the tritan stimulus (t=4.2, p<0.0001). The relationship between defect depths for the luminance and tritan stimuli was dependent on mean defect (r=-0.42, p<0.0001). Discussion: The effort to increase the dynamic range for the chromatic stimuli by increasing the size of the stimulus and using tritan modulation were successful. However, this came at the cost of increased test-retest variability and decreased ability to detect glaucomatous defects. Conclusion: Equiluminant chromatic stimuli in CRT-based tests may not be clinically useful as perimetric stimuli, since increased dynamic range comes at the expense of increased test-retest variability and decreased ability to detect visual loss. Those findings further support the works of Hart (1988) and Sample et al. (2006).
    • Critical Flicker Frequency in Traumatic Brain Injury

      Chang, Tina T. (2008-05-19)
      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.
    • Accommodation to wavefront vergence: adapting ‘averse channels’

      Chen, Angela (2008-06-02)
      Purpose: Accommodation responds to wavefront vergence, but the mechanisms for vergence detection are unknown. One possibility is that accommodation responds to the angle of incidence of light at edges blurred by defocus. ‘Averse channels’ that sample light from opposite sides of the pupil were hypothesized by Makous (1968, 1977). Makous named the phenomenon a “transient” Stiles-Crawford effect because he found that there was a reduction in sensitivity to light entering one side of the pupil that lasts for a short period of time. Such ‘averse channels’ that sample modulation across the pupil are a possible mechanism for detecting the sign of defocus. The purpose of the present experiment is to determine whether such ‘averse channels’ can operate separately of each other to specify the sign of defocus for accommodation. Method: Accommodation was monitored continuously while subjects viewed a vertical monochromatic (548nm) luminance edge (1.0 contrast) that stepped either to a far or near direction in a Badal optometer. Various levels of adapting field were used to reduce the contrast of the edge (0.48, 0.36, 0.26, or 0.17 contrast) to determine the contrast threshold for accommodation. In a final experiment, an adapting field entered the eye through the nasal or temporal side of the pupil, to selectively adapt nasally or temporally tuned ‘channels’, while the target stepped randomly toward or away from the eye. The orientation of the vertical edge was either bright on the right side or bright on the left. Results: In a preliminary experiment, only five out of twenty-six subjects showed reliable and consistent responses, with gains >0.5 for both positive and negative step change in vergence. The contrast threshold for accommodation to step changes in target vergence was approximately 26%. Data from three subjects who accommodated reliably to both directions of step changes in vergence do not support the claim that ‘channels’ sample light separately from opposite sides of the pupil to determine the sign of defocus. Conclusion: Potential factors that account for the poor accommodative responses in the present study include: 1) the target was illuminated with monochromatic light, 2) the target was a simplified stimulus in which the blur was in only one direction (one spatial phase), 3) the target was viewed monocularly, 4) the 3mm artificial pupil increased depth-of-focus and removed the normal dynamic behavior of the pupil, 5) our subjects were untrained. The negative results suggest alternate hypotheses: 1)‘averse channels’ work in conjunction with each other, not separately, to detect vergence, 2) ‘averse channels’ can function separately to detect vergence, but the signal was undetectable using the current method, and 3) ‘averse channels’ do not mediate vergence detection.
    • Accommodation to wavefront vergence and chromatic aberration: color normal and deutan observers

      Wang, Yinan (2009-05-18)
      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).
    • Dynamic and Static Aspects of Accommodation in Mild Traumatic Brain Injury

      Green, Wesley (2009-05-18)
      Purpose: To assess static and dynamic parameters of accommodation in a group of patients with mild traumatic brain injury (mTBI) that reported symptoms associated with near work. Methods: A range of laboratory and clinical measurements of accommodative function were assessed in 12 patients with mTBI, as well as in 10 visually-normal control subjects. Static parameters included push-up and minus-lens accommodative amplitude, positive and negative relative accommodation (PRA/NRA), horizontal and vertical near heterophoria, accommodative convergence-to-accommodation (AC/A) ratio, accommodative stimulus/response function (AS/R), and tonic accommodation. Dynamic parameters included time constant, peak velocity, gain, steady-state response level, steady-state response variability, and accommodative flipper facility rate, including changes in flipper rate after a three-minute fatigue session. Results: All individuals with mTBI manifested a multitude of abnormal accommodative response characteristics. With respect to dynamic parameters, abnormal responses in those with mTBI were found for time constant, peak velocity, accommodative flipper facility fatigue, and steady-state response variability. With respect to static parameters, abnormal values in those with mTBI were found for accommodative amplitude, AC/A ratio, PRA/NRA, and horizontal near heterophoria. Conclusions: The results of the present study provide further evidence that there is a substantial impact of mTBI on accommodative function. With the global nature of the brain insult, it may be presumed that accommodation would be affected by disturbances in various cortical, cerebellar, and/or brainstem areas and along related axonal pathways. Specifically, the reduced peak velocity and related increased time constant found in the mTBI group could be due to damage of neurons carrying accommodative velocity information (i.e., burst cells). This could result in a decrease in either their firing rate or the number of activated cells. The resultant symptoms at near, such as transient blur, can have a negative impact on the overall quality of life and functional capabilities.
    • Triptolide Induces Increases in Migration via Mitogen-activated Protein Kinase Phosphatase-1 control of P38 and JNK MAPK Activation

      Parekh, Nili M. (2010-07-16)
      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.
    • Nearwork-Induced Transient Myopia (NITM) Following Marked and Sustained, but Interrupted, Accommodation at Near

      Arunthavaraja, Mathangi (2010-07-16)
      Purpose: It has been speculated that non-decayed NITM (accommodatively-based nearwork-induced transient myopia) may be myopigenic in nature. Thus, the purpose of the present investigation was to determine objectively the initial magnitude and decay of NITM, and its potential additivity, following successive but interrupted periods of marked, sustained accommodation at near in asymptomatic young-adult myopic subjects. Methods: Fifteen visually-normal, asymptomatic young adults (ages 18 – 28 years) were tested with full distance refractive correction. They included 9 early-onset (EOM) and 6 late-onset (LOM) myopic subjects. Accommodation was assessed objectively with a Canon R-1, open-field, infrared auto-refractor under monocular viewing conditions (RE). The distance refractive state was measured immediately before and after a ten minute period of focusing upon a moderate contrast (50%), very near target (12 cm; 8D) subtending a visual angle of 1 degree. The task was repeated twice with a 5-minute inter-task rest period of imposed far viewing. NITM was defined as the post-task minus pre-task change in distance refractive state immediately following each task. Results: Significant amounts of NITM were generated following nearly each trial in each subject. These ranged from 0.11 to 0.71D, with a mean of 0.31D. The group mean NITM was 0.32, 0.29, and 0.31D for trials 1, 2, and 3, respectively. For the EOMs subgroup, NITM was 0.28, 0.30, and 0.34D, while for the LOMs subgroup, it was 0.38, 0.29, and 0.26D, for for trials 1, 2, and 3, respectively. Decay of NITM was prolonged in many of the subjects (67%). However, additivity of NITM was not found following the sequences of interrupted near tasks. Conclusions: There was no evidence of NITM additivity following a marked and sustained, but interrupted, near task. Although NITM has been reported to be additive following long periods of uninterrupted and sustained reading at lower dioptric levels, providing rest periods between each near task trial appears to prevent a cumulative effect (i.e., additivity effect). These findings support the idea of far viewing being protective in nature from myopia development.
    • Reading from an Electronic Reading Device versus Hardcopy Text

      Hue, Jennifer E. (2013-06-24)
      The use of electronic reading devices has become more prevalent. Many individuals of all ages are using personal electronic readers (e.g., Kindle, Nook, E-Reader) in place of hardcopy printed materials. Previous work in our laboratory has demonstrated that symptoms when reading from a computer screen are significantly greater than those experienced when reading printed text. Accordingly, the aim of the present study was to examine both symptoms and task performance when reading from a Kindle e-reading device, and to compare the findings with those from hardcopy, printed materials.
    • Exploring the veridicality of shape-from-shading for real 3D objects

      Bartov, Jenny (2016-05)
      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.
    • 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.
    • 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.