In the antisaccade task participants are required to saccade to the mirror image location of a sudden onset target. As such, the task provides a powerful tool with which to investigate the cognitive processes underlying goal-directed behaviour. In healthy participants antisaccade errors (prosaccades directed towards the target) occur on approximately 20% of trials, and increased antisaccade error rate is widely used as a measure of “cognitive disinhibition” in clinical settings. One aspect of antisaccade performance that has received relatively little attention is the large variability in error rate typically observed within healthy participants. Whilst there are many studies describing increased antisaccade error rates in patient populations, there has been comparatively little research into what individual differences might underlie the dramatic variations that are observed within healthy participants. This thesis presents five papers, each of which explores potential sources of variability in antisaccade performance in healthy participants. The first paper used a cueing manipulation to explore the extent to which individual differences in the ability to maintain the task goal in mind will influence antisaccade error rate. The second paper addressed the potential role of differences in motivation, by determining the extent to which antisaccade performance is moderated by a range of incentives. In paper 3, the role of strategic influences was investigated by altering the task instructions that participants were given. In paper 4, task instructions and working memory load were manipulated in order to determine their effect on antisaccade error awareness. The final paper, based on data gathered across the preceding experiments, explored the extent to which individual differences in factors such as working memory capacity, processing speed, and personality measures (schizotypy and impulsivity) correlated with antisaccade performance. Across all studies, the data is used to test predictions made by current parallel programming models of antisaccade performance. The data suggests that a range of “top-down” factors can influence antisaccade performance, but that the most important individual difference in explaining antisaccade error rate in healthy participants is prosaccade latency.

Aims The aim of this PhD research project was to investigate the application of dental pulp stem cells (DPSC) as a treatment for traumatic and degenerative eye diseases. The accuracy and reliability of counting retinal ganglion cells (RGC) in radial retinal section was also assessed. Methods Numbers of RGC in radial retinal sections were compared to numbers in retinal wholemounts. DPSC were cultured with RGC and survival and neuritogenesis were quantified. DPSC were also transplanted intravitreally into rat models of optic neuropathy (optic nerve crush) and glaucoma and surviving RGC and regenerated axons were quantified in radial retinal sections. Results Quantifying RGC in radial retinal sections was as reliable and accurate as the current gold standard Thus, retinal wholemounts with Brn3a proved to be the most reliable marker for RGC. DPSC protected RGC from optic nerve crush-/glaucoma-induced death, promoting significant regeneration of RGC axons in the former and preserving visual function (as measured by electroretinography) in the latter. The mechanism of action, as determined in vitro, appeared to be through the secretion of multiple neurotrophic factors (NTF). Conclusions In conclusion, DPSC is a potent cell therapy in the treatment of traumatic and degenerative eye disease.

Glaucoma is defined as a progressive optic neuropathy, characterized by loss of visual function and often associated with high intra-ocular pressure. Testing the patients' visual function with Standard Automated Perimetry (SAP) is currently the clinical standard for detecting glaucomatous visual field loss. A new test algorithm using the Frequency Doubling illusion has been introduced on the Matrix perimeter (Humphrey Matrix; Carl Zeiss Meditech, Dublin CA) that measures the central 10° using a 2°x 2° square flickering stimulus. This stimulus has the theoretical advantage of being both a large target, with good repeatability, and being perceptually selective, by preferentially stimulating the magnocellular projecting ganglion cells. <br /><br /> The purpose of this thesis was to determine the within-technique, between-visits repeatability and the within-visit, between-technique comparison of several techniques available to measure the central 10° visual field in patients with late stage glaucoma. In particular, to examine test-retest variability and compare sensitivity threshold values, visual field indices, and total and pattern deviation probability maps among the following techniques: Full Threshold SAP 10-2 size III (SAP III), Full Threshold SAP size V (SAP V), SITA SAP 10-2 size III (SS III), and Matrix 10-2 2° stimulus (M2). <br /><br /> Forty nine patients with advanced glaucomatous visual field defects attended 3 visits. During each visit, 1 eye was examined with each of the 4 techniques mentioned above. Data from the first visit was discarded to eliminate bias that may occur from the learning effect. Coefficient of Repeatability values of SAP III, SAP V, SS III, and M2 were calculated to be 10. 33, 9. 00, 9. 90, and 12. 04%dB respectively, relative to the average difference in threshold estimates between visits. M2 had the most uniform test-retest characteristics across the full range of sensitivities; however the 90% confidence interval was the widest of all techniques in the normal to near normal range (24 to 38dB). M2 showed the greatest defects in both total and pattern deviation probability plots. Threshold estimates of SAP III and SS III were shown to be similar and slightly more variable than SAP V. M2 showed greater defects than SAP III in both total and pattern deviation probability plots. Compared to SAP III and SS, M2 estimated sensitivity as less severe. Estimates of 20 dB and above on M2 were estimated at approximately 30 dB with SAP V. In the moderate to abnormal sensitivity range, Matrix estimated points to be shallower than that estimated by SAP V. <br /><br /> This thesis showed that test-retest variability of the SAP techniques decreased with increasing sensitivity whereas; variability was constant throughout the dynamic range for M2 and smaller in the moderate to severe range. However M2 was worst in the normal to near-normal sensitivity range. This suggests that M2, compared to all SAP techniques, will be disadvantaged for the detection of early visual field loss but better positioned to repeatably detect and follow moderate to severe loss in the central 10° of patients with late stage glaucoma.

Glaucoma is defined as a progressive optic neuropathy, characterized by loss of visual function and often associated with high intra-ocular pressure. Testing the patients' visual function with Standard Automated Perimetry (SAP) is currently the clinical standard for detecting glaucomatous visual field loss. A new test algorithm using the Frequency Doubling illusion has been introduced on the Matrix perimeter (Humphrey Matrix; Carl Zeiss Meditech, Dublin CA) that measures the central 10° using a 2°x 2° square flickering stimulus. This stimulus has the theoretical advantage of being both a large target, with good repeatability, and being perceptually selective, by preferentially stimulating the magnocellular projecting ganglion cells. <br /><br /> The purpose of this thesis was to determine the within-technique, between-visits repeatability and the within-visit, between-technique comparison of several techniques available to measure the central 10° visual field in patients with late stage glaucoma. In particular, to examine test-retest variability and compare sensitivity threshold values, visual field indices, and total and pattern deviation probability maps among the following techniques: Full Threshold SAP 10-2 size III (SAP III), Full Threshold SAP size V (SAP V), SITA SAP 10-2 size III (SS III), and Matrix 10-2 2° stimulus (M2). <br /><br /> Forty nine patients with advanced glaucomatous visual field defects attended 3 visits. During each visit, 1 eye was examined with each of the 4 techniques mentioned above. Data from the first visit was discarded to eliminate bias that may occur from the learning effect. Coefficient of Repeatability values of SAP III, SAP V, SS III, and M2 were calculated to be 10. 33, 9. 00, 9. 90, and 12. 04%dB respectively, relative to the average difference in threshold estimates between visits. M2 had the most uniform test-retest characteristics across the full range of sensitivities; however the 90% confidence interval was the widest of all techniques in the normal to near normal range (24 to 38dB). M2 showed the greatest defects in both total and pattern deviation probability plots. Threshold estimates of SAP III and SS III were shown to be similar and slightly more variable than SAP V. M2 showed greater defects than SAP III in both total and pattern deviation probability plots. Compared to SAP III and SS, M2 estimated sensitivity as less severe. Estimates of 20 dB and above on M2 were estimated at approximately 30 dB with SAP V. In the moderate to abnormal sensitivity range, Matrix estimated points to be shallower than that estimated by SAP V. <br /><br /> This thesis showed that test-retest variability of the SAP techniques decreased with increasing sensitivity whereas; variability was constant throughout the dynamic range for M2 and smaller in the moderate to severe range. However M2 was worst in the normal to near-normal sensitivity range. This suggests that M2, compared to all SAP techniques, will be disadvantaged for the detection of early visual field loss but better positioned to repeatably detect and follow moderate to severe loss in the central 10° of patients with late stage glaucoma.

The optical properties of Fresnel reflections from the human ocular surfaces, called Purkinje reflections, are examined. Extensive modeling of the behavior of the reflection of sources from the front of the cornea and the front of the crystalline lens with real rays in lens design software is presented. The modeling looks at the effects of various conic constant values on the ocular surfaces and rotation of the eye in particular. First and third Purkinje images were collected from 14 subjects for varying fixation positions to compare with modeling. The results showed a decrease in third Purkinje image height as the eye rotated from gazing at a point near the light sources to a point near the optical axis of the imaging camera. This matched the predictions from modeling and indicates that fixation position is an important factor in the accuracy and repeatability of comparison phakometry results. Schematic eye models were set up for each subject and the anterior lens radius of curvature and conic constant were optimized to match the collected Purkinje image height data. The mean conic constant estimate from optimization was -3.82 with a standard deviation of 1.51. The schematic eye models did not include crystalline lens tilt or individual corneal conic constant values, each of which is estimated to contribute an uncertainty of ± 0.5 in the anterior lens conic constant value. This is the first use of Purkinje images to assess anterior lens conic constant values.

Chemotaxis and cell migration are important processes for life, involved in organism development and homeostasis and implicated in a number of disease states. Dictyostelium discoideum, an amoeba, is a useful model for investigation of chemotaxis and development, due to its ability to undergo chemotactic aggregation and development upon starvation. Although cell migration has been well described on planar transparent surfaces, it is uncertain how well these conditions replicate the natural environment of a cell. However, attempts to better replicate these environments generally make use of opaque substrates and 3D matrices, in which it is more challenging to image cell migration. Protocols were developed to enable optical coherence tomography, a 3D structural imaging technique which requires no sample processing or staining, to be successfully employed in imaging Dictyostelium cell migration in time-lapse on non-transparent substrata and within an agarose gel. I compared the effects of two substrates, a nitrocellulose filter and a polystyrene Petri dish on aggregating cells and found differences in speed but not persistence. Extension of this to include cells within agarose revealed that these cells exhibited less directed migration, but their velocity was unaffected. I showed that cells lacking myosin II failed to complete development within an agarose gel and had significantly reduced velocity and directional migration when compared to their parent strain. Furthermore, the velocities of cells migrating within agarose gel were bimodally distributed, potentially indicating two distinct cell populations, fast and slow, and fast movement was shown to be largely myosin II dependent. Great potential therefore exists for cell-substrate and cell-matrix interactions to affect the migration character of cells, even those, such as Dictyostelium, which do not form strong focal adhesions. Moreover a properly ordered cytoskeleton is implicated in enabling cells to effectively utilise different modes of cell motility.

No description available.

The delivery of drugs plays an important role in the treatment of ocular diseases. In this thesis, biocompatible, biodegradable materials such as poly(propylene fumarate) (PPF) and poly(lactic-co-glycolic) (PLGA) were used to prepare delivery systems. PPF together with N-vinyl pyrrolidone (NVP) was photo-crosslinked to generate monolithic polymer rods, which were loaded with either acetazolamide (AZ), dichlorphenamide (DP) or timolol maleate (TM). The release kinetics and structural properties were determined as well as the in vivo degradation. Further studies were performed to examine the influence of PPF molecular weight and the ratio of PPF/PNVP on the release kinetics. In addition, a coaxial electrospinning setup was developed to fabricate PLGA fiber networks as a delivery system. We found that prefabricated, photo-crosslinked PPF/PNVP matrices represent suitable, controllable release systems for different drugs. Furthermore, coaxial electrospinning is a promising technique to generate scaffolds for drug delivery.

This thesis investigates the dynamic characteristics of fast phase eye movements in the Vestibulo-Ocular Reflex (VOR) and their application in vestibular lesion clinics. Eye responses in the VOR consist of alternations between slow phases (eye moves opposite to head) to stablize the eye in space and fast phases to quickly redirect the eye in space. At the end of each fast phase segment, the eye position appears well correlated with head velocity. In contrast to slow phases, fast phases are of quite short duration. Therefore, they must be detected precisely in order to do any further analysis. This thesis reports an improved version of a previous autoregression (ARX) model classification algorithm, to allow automatic classification of fast phase segments or to detect only end points of fast phases. / Results in this thesis demonstrate that the dynamics associated with the fast phase end points present specific patterns. These patterns can be represented as a linear or a cubic equation. In other words, a first-order or third-order polynomial can be fitted to the experimental data by the least square technique. The DC bias of the fitted data shows distinctive ranges for normal subjects and vestibular lesion patients. The asymmetric an non-linear shapes of the fitted curve can also denote a lesion. Other dynamic properties, such as the fast phase segment frequencies or the phase shift between the output eye position and input head velocity, have strong tendencies to differentiate normals from patients. In addition, the characteristics of fast phase beginning points suggest that the initiation of fast phases in independent of any obvious eye velocity or eye position threshold.

In order to investigate if the ERG could be used to monitor the function of the retina as it is adapting to a new luminous environment, we measured the impact of pre-exposure to a bright luminous environment on the electrical response of the retina recorded (1) immediately after closure of this bright background luminance (i.e., at the onset of dark adaptation) and (2) immediately after a reduction of the background luminance from a brighter to a dimmer level. Our experimental approach resulted in highly significant and transient modifications in the amplitudes and in the peak times of most of the ERG components. This study also lead to a reinterpretation of the genesis of the oscillatory potentials as well as of the origin of the Light Adaptation Effect, a not yet explained retinal phenomenon previously reported by several investigators. We believe that our procedure could have a significant clinical value, as it seems to be suggested with our results obtained from two patients affected with congenital stationary night blindness with myopia.