Assessment of the oculomotor response in human factor environments

The need to measure the response of the oculomotor system, such as ocular accommodation, accurately and in real-world environments is essential. New instruments have been developed over the past 50 years to measure eye focus including the extensively utilised and well validated Canon R-1, but in general these have had limitations such as a closed field-of-view, a poor temporal resolution and the need for extensive instrumentation bulk preventing naturalistic performance of environmental tasks. The use of photoretinoscopy and more specifically the PowerRefractor was examined in this regard due to its remote nature, binocular measurement of accommodation, eye movement and pupil size and its open field-of-view. The accuracy of the PowerRefractor to measure refractive error was on averaging similar, but more variable than subjective refraction and previously validated instrumentation. The PowerRefractor was found to be tolerant to eye movements away from the visual axis, but could not function with small pupil sizes in brighter illumination. The PowerRefractor underestimated the lead of accommodation and overestimated the slope of the accommodation stimulus response curve. The PowerRefractor and the SRW-5000 were used to measure the oculomotor responses in a variety of real-world environment: spectacles compared to single vision contract lenses; the use of multifocal contact lenses by pre-presbyopes (relevant to studies on myopia retardation); and ‘accommodating’ intraocular lenses. Due to the accuracy concerns with the PowerRefractor, a purpose-built photoretinoscope was designed to measure the oculomotor response to a monocular head-mounted display. In conclusion, this thesis has shown the ability of photoretinoscopy to quantify changes in the oculomotor system. However there are some major limitations to the PowerRefractor, such as the need for individual calibration for accurate measures of accommodation and vergence, and the relatively large pupil size necessary for measurement.

An optical study of human ocular dimensions

Many workers have studied the ocular components which occur in eyes exhibiting differing amounts of central refractive error but few have ever considered the additional information that could be derived from a study of peripheral refraction. Before now, peripheral refraction has either been measured in real eyes or has otherwise been modelled in schematic eyes of varying levels of sophistication. Several differences occur between measured and modelled results which, if accounted for, could give rise to more information regarding the nature of the optical and retinal surfaces and their asymmetries. Measurements of ocular components and peripheral refraction, however, have never been made in the same sample of eyes. In this study, ocular component and peripheral refractive measurements were made in a sample of young near-emmetropic, myopic and hyperopic eyes. The data for each refractive group was averaged. A computer program was written to construct spherical surfaced schematic eyes from this data. More sophisticated eye models were developed making use of linear algebraic ray tracing program. This method allowed rays to be traced through toroidal aspheric surfaces which were translated or rotated with respect to each other. For simplicity, the gradient index optical nature of the crystalline lens was neglected. Various alterations were made in these eye models to reproduce the measured peripheral refractive patterns. Excellent agreement was found between the modelled and measured peripheral refractive values over the central 70o of the visual field. This implied that the additional biometric features incorporated in each eye model were representative of those which were present in the measured eyes. As some of these features are not otherwise obtainable using in vivo techniques, it is proposed that the variation of refraction in the periphery offers a very useful optical method for studying human ocular component dimensions.

Measurement of ocular component contributions to residual astigmatism in adult human eyes

The aim of this study was to determine whether an ophthalmophakometric technique could offer a feasible means of investigating ocular component contributions to residual astigmatism in human eyes. Current opinion was gathered on the prevalence, magnitude and source of residual astigmatism. It emerged that a comprehensive evaluation of the astigmatic contributions of the eye's internal ocular surfaces and their respective axial separations (effectivity) had not been carried out to date. An ophthalmophakometric technique was developed to measure astigmatism arising from the internal ocular components. Procedures included the measurement of refractive error (infra-red autorefractometry), anterior corneal surface power (computerised video keratography), axial distances (A-scan ultrasonography) and the powers of the posterior corneal surface in addition to both surfaces of the crystalline lens (multi-meridional still flash ophthalmophakometry). Computing schemes were developed to yield the required biometric data. These included (1) calculation of crystalline lens surface powers in the absence of Purkinje images arising from its anterior surface, (2) application of meridional analysis to derive spherocylindrical surface powers from notional powers calculated along four pre-selected meridians, (3) application of astigmatic decomposition and vergence analysis to calculate contributions to residual astigmatism of ocular components with obliquely related cylinder axes, (4) calculation of the effect of random experimental errors on the calculated ocular component data. A complete set of biometric measurements were taken from both eyes of 66 undergraduate students. Effectivity due to corneal thickness made the smallest cylinder power contribution (up to 0.25DC) to residual astigmatism followed by contributions of the anterior chamber depth (up to 0.50DC) and crystalline lens thickness (up to 1.00DC). In each case astigmatic contributions were predominantly direct. More astigmatism arose from the posterior corneal surface (up to 1.00DC) and both crystalline lens surfaces (up to 2.50DC). The astigmatic contributions of the posterior corneal and lens surfaces were found to be predominantly inverse whilst direct astigmatism arose from the anterior lens surface. Very similar results were found for right versus left eyes and males versus females. Repeatability was assessed on 20 individuals. The ophthalmophakometric method was found to be prone to considerable accumulated experimental errors. However, these errors are random in nature so that group averaged data were found to be reasonably repeatable. A further confirmatory study was carried out on 10 individuals which demonstrated that biometric measurements made with and without cycloplegia did not differ significantly.

The development of calibration and adaptive filtering procedures for neuromagnetic studies of human visual function

This thesis first considers the calibration and signal processing requirements of a neuromagnetometer for the measurement of human visual function. Gradiometer calibration using straight wire grids is examined and optimal grid configurations determined, given realistic constructional tolerances. Simulations show that for gradiometer balance of 1:104 and wire spacing error of 0.25mm the achievable calibration accuracy of gain is 0.3%, of position is 0.3mm and of orientation is 0.6°. Practical results with a 19-channel 2nd-order gradiometer based system exceed this performance. The real-time application of adaptive reference noise cancellation filtering to running-average evoked response data is examined. In the steady state, the filter can be assumed to be driven by a non-stationary step input arising at epoch boundaries. Based on empirical measures of this driving step an optimal progression for the filter time constant is proposed which improves upon fixed time constant filter performance. The incorporation of the time-derivatives of the reference channels was found to improve the performance of the adaptive filtering algorithm by 15-20% for unaveraged data, falling to 5% with averaging. The thesis concludes with a neuromagnetic investigation of evoked cortical responses to chromatic and luminance grating stimuli. The global magnetic field power of evoked responses to the onset of sinusoidal gratings was shown to have distinct chromatic and luminance sensitive components. Analysis of the results, using a single equivalent current dipole model, shows that these components arise from activity within two distinct cortical locations. Co-registration of the resulting current source localisations with MRI shows a chromatically responsive area lying along the midline within the calcarine fissure, possibly extending onto the lingual and cuneal gyri. It is postulated that this area is the human homologue of the primate cortical area V4.

Optimising the clinical analysis of retinal image quality in the human eye

Visual perception is dependent on both light transmission through the eye and neuronal conduction through the visual pathway. Advances in clinical diagnostics and treatment modalities over recent years have increased the opportunities to improve the optical path and retinal image quality. Higher order aberrations and retinal straylight are two major factors that influence light transmission through the eye and ultimately, visual outcome. Recent technological advancements have brought these important factors into the clinical domain, however the potential applications of these tools and considerations regarding interpretation of data are much underestimated. The purpose of this thesis was to validate and optimise wavefront analysers and a new clinical tool for the objective evaluation of intraocular scatter. The application of these methods in a clinical setting involving a range of conditions was also explored. The work was divided into two principal sections: 1. Wavefront Aberrometry: optimisation, validation and clinical application The main findings of this work were: • Observer manipulation of the aberrometer increases variability by a factor of 3. • Ocular misalignment can profoundly affect reliability, notably for off-axis aberrations. • Aberrations measured with wavefront analysers using different principles are not interchangeable, with poor relationships and significant differences between values. • Instrument myopia of around 0.30D is induced when performing wavefront analysis in non-cyclopleged eyes; values can be as high as 3D, being higher as the baseline level of myopia decreases. Associated accommodation changes may result in relevant changes to the aberration profile, particularly with respect to spherical aberration. • Young adult healthy Caucasian eyes have significantly more spherical aberration than Asian eyes when matched for age, gender, axial length and refractive error. Axial length is significantly correlated with most components of the aberration profile. 2. Intraocular light scatter: Evaluation of subjective measures and validation and application of a new objective method utilising clinically derived wavefront patterns. The main findings of this work were: • Subjective measures of clinical straylight are highly repeatable. Three measurements are suggested as the optimum number for increased reliability. • Significant differences in straylight values were found for contact lenses designed for contrast enhancement compared to clear lenses of the same design and material specifications. Specifically, grey/green tints induced significantly higher values of retinal straylight. • Wavefront patterns from a commercial Hartmann-Shack device can be used to obtain objective measures of scatter and are well correlated with subjective straylight values. • Perceived retinal stray light was similar in groups of patients implanted with monofocal and multi focal intraocular lenses. Correlation between objective and subjective measurements of scatter is poor, possibly due to different illumination conditions between the testing procedures, or a neural component which may alter with age. Careful acquisition results in highly reproducible in vivo measures of higher order aberrations; however, data from different devices are not interchangeable which brings the accuracy of measurement into question. Objective measures of intraocular straylight can be derived from clinical aberrometry and may be of great diagnostic and management importance in the future.

Biomechanical aspects of the anterior segment in human myopia

The thesis investigates the relationship between the biomechanical properties of the anterior human sclera and cornea in vivo using Schiotz tonometry (ST), rebound tonometry (RBT, iCare) and the Ocular Response Analyser (ORA, Reichert). Significant differences in properties were found to occur between scleral quadrants. Structural correlates for the differences were examined using Partial Coherent Interferometry (IOLMaster, Zeiss), Optical Coherent tomography (Visante OCT), rotating Scheimpflug photography (Pentacam, Oculus) and 3-D Magnetic Resonance Imaging (MRI). Subject groups were employed that allowed investigation of variation pertaining to ethnicity and refractive error. One hundred thirty-five young adult subjects were drawn from three ethnic groups: British-White (BW), British-South-Asian (BSA) and Hong-Kong-Chinese (HKC) comprising non-myopes and myopes. Principal observations: ST demonstrated significant regional variation in scleral resistance a) with lowest levels at quadrant superior-temporal and highest at inferior-nasal; b) with distance from the limbus, anterior locations showing greater resistance. Variations in resistance using RBT were similar to those found with ST; however the predominantly myopic HKC group had a greater overall mean resistance when compared to the BW-BSA group. OCT-derived scleral thickness measurements indicated the sclera to be thinner superiorly than inferiorly. Thickness varied with distance from the corneolimbal junction, with a decline from 1 to 2 mm followed by a successive increase from 3 to 7 mm. ORA data varied with ethnicity and refractive status; whilst axial length (AL) was associated with corneal biometrics for BW-BSA individuals it was associated with IOP in the HKC individuals. Complex interrelationships were found between ORA Additional-Waveform-Parameters and biometric data provided by the Pentacam. OCT indicated ciliary muscle thickness to be greater in myopia and more directly linked to posterior ocular volume (from MRI) than AL. Temporal surface areas (SAs, from MRI) were significantly smaller than nasal SAs in myopic eyes; globe bulbosity (from MRI) was constant across quadrants.

Force sensing for measuring human body movement

The research developed in this thesis explores the sensing and inference of human movement in a dynamic way, as opposed to conventional measurement systems, that are only concerned with discrete evaluations of stimuli in sequential time. Typically, conventional approaches are used to infer the dynamic movement of the body; such as vision and motion tracking devices, with either a human diagnosis or complex image processing algorithm to classify the movement. This research is therefore the first of its kind to attempt and provide a movement classifying algorithm through the use of minimal sensing points, with the application for this novel system, to classify human movement during a golf swing. There are two main categories of force sensing. Firstly, array-type systems consisting of many sensing elements, and are the most commonly researched and commercially available. Secondly, reduced force sensing element systems (RFSES) also known as distributive systems have only been recently exploited in the academic world. The fundamental difference between these systems is that array systems handle the data captured from each sensor as unique outputs and suffer the effects of resolution. The effect of resolution, is the error in the load position measurement between sensing elements, as the output is quantized in terms of position. This can be compared to a reduced sensor element system that maximises that data received through the coupling of data from a distribution of sensing points to describe the output in discrete time. Also this can be extended to a coupling of transients in the time domain to describe an activity or dynamic movement. It is the RFSES that is to be examined and exploited in the commercial sector due to its advantages over array-based approaches such as reduced design, computational complexity and cost.

Ocular biometric correlates of ciliary muscle thickness in human myopia

Purpose - Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. Methods - Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18–40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) =-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. Results - MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. Conclusions - Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.

Improving the Watermarking Process with Usage of Block Error-Correcting Codes

The emergence of digital imaging and of digital networks has made duplication of original artwork easier. Watermarking techniques, also referred to as digital signature, sign images by introducing changes that are imperceptible to the human eye but easily recoverable by a computer program. Usage of error correcting codes is one of the good choices in order to correct possible errors when extracting the signature. In this paper, we present a scheme of error correction based on a combination of Reed-Solomon codes and another optimal linear code as inner code. We have investigated the strength of the noise that this scheme is steady to for a fixed capacity of the image and various lengths of the signature. Finally, we compare our results with other error correcting techniques that are used in watermarking. We have also created a computer program for image watermarking that uses the newly presented scheme for error correction.

Robotic Outcome Assessment in a Non-Human Primate Model of Middle Cerebral Artery Stroke

Stroke is a prevalent disorder with immense socioeconomic impact. A variety of chronic neurological deficits result from stroke. In particular, sensorimotor deficits are a significant barrier to achieving post-stroke independence. Unfortunately, the majority of pre-clinical studies that show improved outcomes in animal stroke models have failed in clinical trials. Pre-clinical studies using non-human primate (NHP) stroke models prior to initiating human trials are a potential step to improving translation from animal studies to clinical trials. Robotic assessment tools represent a quantitative, reliable, and reproducible means to assess reaching behaviour following stroke in both humans and NHPs. We investigated the use of robotic technology to assess sensorimotor impairments in NHPs following middle cerebral artery occlusion (MCAO). Two cynomolgus macaques underwent transient MCAO for 90 minutes. Approximately 1.5 years following the procedure these NHPs and two non-stroke control monkeys were trained in a reaching task with both arms in the KINARM exoskeleton. This robot permits elbow and shoulder movements in the horizontal plane. The task required NHPs to make reaching movements from a centrally positioned start target to 1 of 8 peripheral targets uniformly distributed around the first target. We analyzed four movement parameters: reaction time, movement time (MT), initial direction error (IDE), and number of speed maxima to characterize sensorimotor deficiencies. We hypothesized reduced performance in these attributes during a neurobehavioural task with the paretic limb of NHPs following MCAO compared to controls. Reaching movements in the non-affected limbs of control and experimental NHPs showed bell-shaped velocity profiles. In contrast, the reaching movements with the affected limbs were highly variable. We found distinctive patterns in MT, IDE, and number of speed peaks between control and experimental monkeys and between limbs of NHPs with MCAO. NHPs with MCAO demonstrated more speed peaks, longer MTs, and greater IDE in their paretic limb compared to controls. These initial results qualitatively match human stroke subjects’ performance, suggesting that robotic neurobehavioural assessment in NHPs with stroke is feasible and could have translational relevance in subsequent human studies. Further studies will be necessary to replicate and expand on these preliminary findings.

MRI Registration for Human Hip Kinematics

Measurement of joint kinematics can provide knowledge to help improve joint prosthesis design, as well as identify joint motion patterns that may lead to joint degeneration or injury. More investigation into how the hip translates in live human subjects during high amplitude motions is needed. This work presents a design of a non-invasive method using the registration between images from conventional Magnetic Resonance Imaging (MRI) and open MRI to calculate three dimensional hip joint kinematics. The method was tested on a single healthy subject in three different poses. MRI protocols for the conventional gantry, high-resolution MRI and the open gantry, lowresolution MRI were developed. The scan time for the low-resolution protocol was just under 6 minutes. High-resolution meshes and low resolution contours were derived from segmentation of the high-resolution and low-resolution images, respectively. Low-resolution contours described the poses as scanned, whereas the meshes described the bones’ geometries. The meshes and contours were registered to each other, and joint kinematics were calculated. The segmentation and registration were performed for both cortical and sub-cortical bone surfaces. A repeatability study was performed by comparing the kinematic results derived from three users’ segmentations of the sub-cortical bone surfaces from a low-resolution scan. The root mean squared error of all registrations was below 1.92mm. The maximum range between segmenters in translation magnitude was 0.95mm, and the maximum deviation from the average of all orientations was 1.27◦. This work demonstrated that this method for non-invasive measurement of hip kinematics is promising for measuring high-range-of-motion hip motions in vivo.

Social Influences of Error Monitoring

Adolescence is characterized by dramatic hormonal, physical, and psychological changes, and is a period of risk for affective and anxiety disorders. Pubertal development during adolescence plays a major role in the emergence of these disorders, particularly among girls. Thus, it is critical to identify early biomarkers of risk. One potential biomarker, the error-related negativity (ERN), is an event-related potential following an erroneous response. Individuals with an anxiety disorder demonstrate a greater ERN than healthy comparisons, an association which is stronger in adolescence, suggesting that pubertal development may play a role in the ERN as a predictor of anxiety. One form of anxiety often observed in adolescence, particularly among girls, is social anxiety, which is defined as anxiety elicited by social-evaluative contexts. In adults, enhancements of the ERN in social-evaluative contexts is positively related to social anxiety symptoms, suggesting that the ERN in social contexts may serve as a biomarker for social anxiety. This dissertation examined the ERN in and its relation with puberty and social anxiety among 76 adolescent girls. Adolescent girls completed a flanker task in two different