Ei indicates the eccentricity where stimulus size must double to maintain performance equivalent to that at fovea. An over 200-fold range of Ei has been found using spatial scaling since the introduction of method. Some later research in orientation discrimination suggested that contrast reduction elevated Ei (Sally and Gurnesy 2003, 2004 and 2007). However, it was based on very limited data. Therefore, to examine how Ej changes with contrast, two types of orientation discrimination tasks involving six experiments were studied using spatial scaling in the thesis: (i) orientation discrimination at 10-100% contrasts and 0-10 degree eccentricities using Gaussian-filtered lines and 2-16 cycles-per-image (cpi) gratings, and (ii) contrast thresholds allowing discrimination of 1.5-45 degrees orientation differences (OD) at 0-10 degree eccentricities using the same stimuli for the first task. Three hypotheses were made: (i) when the effect of contrast was taken into account, the peripheral stimulus size required for performance equivalent to that of the fovea can be obtained at a range of contrasts by spatial scaling, and (ii) for low-cycle-number (<16 cpi) grating stimulus, the number of cycles played a crucial role on the visual performance across visual field, and (iii) for the threshold contrast of a fixed orientation difference discrimination, the visual process mechanism of the visual task at large orientation difference was different from that at small difference close to orientation discrimination threshold. The results of the orientation discrimination experiments showed that (i) spatial scaling succeeded in superimposing all the threshold data across contrasts or within a contrast, meaning that there is no qualitative difference between the fovea and periphery, (ii) E2 was independent of contrast, suggesting that contrast reduction had no different influence on spatial summation in between foveal and peripheral visual field, (iii) Ei decreased and saturated with increasing cpi, indicating that for low-cycle-number grating stimulus, the cycle number played a crucial role on the visual performance. The results of the contrast threshold allowing the fixed orientation discrimination experiments showed that (i) the task complexity resulted in the failure of spatial scaling for superimposing all the threshold data across orientation differences, (ii) spatial Ei increased and saturated with increasing cpi, suggesting more size scaling needed for achieving foveal levels of performance for smaller cpi stimulus, and (iii) Ej found in 1.5 deg orientation difference was much smaller than those at other differences, suggesting that the visual process mechanism at large OD was different from that at OD as small as orientation discrimination threshold.

This project is to investigate retinal plasticity at the cellular level, i.e. changes of the cell density, cell pattern, cell morphology and the perineuronal net, in the aged and glaucomatous retinas. A multiphoton-DAPI method was developed to study retinal transneuronal degeneration. In glaucoma, the neurodegeneration at the retinal ganglion cell layer (RGCL) initiates a cascade of transneuronal degeneration in the inner nucleus layer (INL) and the outer nucleus layer (ONL). On the other hand, in ageing, neurons in both the RGCL and ONL are markedly affected the neuronal loss in the INL correlates with both layers. This suggests other mechanisms in addition to transneuronal degeneration that contribute to the retinal degeneration in ageing. In glaucoma, the pattern of the neuronal loss in the RGCL was analysed. Supported by the microscopic observation, nearest neighbour analysis (NNA) reveals a combination of diffuse and clustered patterns of neuronal loss. In particular, the diffuse pattern was more common in the central retina whereas the clustered loss was prominent in the mid- peripheral retina. It is very likely that these two patterns of neuronal loss were produced by two different pathologic mechanisms leading to RGC depletion. There appear to be differences between the chondroitin glycosaminoglycan (CS-GAG) staining and the aggrecan core protein staining in the RGCL, INL and the inner plexiform layer. This suggests that some of the GAG attachment regions of aggrecan have been removed in these domains. The major source of CS-GAG staining appears to be from aggrecan because only negative staining for decorin, biglycan, lumican, keratocan and versican was found. Also, negative 5D4 staining suggests that this aggrecan is not or minimally substituted with keratocan sulphate. This study emphasises the importance of the perineuronal net in potentially restricting the recovery and regeneration of neurons in the adult retina.

Autosomal dominant optic atrophy (ADOA) is a slowly progressive ocular disorder associated with retinal ganglion cell loss and optic atrophy, manifesting with a variable reduction in visual acuity, colour vision defects and visual field loss. Genetic studies lead to the identification of mutations in the OPA1 gene on chromosome 3q28-qter, which is the main ADOA-causing gene. OPA1 is an ubiquitously expressed, nuclear dynamin-related GTPase, targeted to the inner mitochondrial membrane, which plays a role in mitochondrial fusion and ultimately has a protective role against apoptosis. In order to study the pathophysiology of ADOA, a new ENU-induced mutant mouse carrying a protein truncating nonsense mutation in Opal has been generated in our laboratory (B6 C3-OpalQ285STOP). The heterozygous mutation leads to approximately 50% reduction in Opal protein in mitochondria from retinal samples studied by Western blot. The homozygous mutation is embryonic lethal. The phenotype of heterozygous mutant mice is not associated with a severe neuro-degenerative process, in keeping with the variable and relatively mild phenotype observed in many patients with ADOA. Thus, visual phenotyping shows reduced visual function and electron microscopy reveals significant abnormalities in myelin bundles and increased autophagy with increasing age up to two years. Despite this, heterozygous adult mutants (up to 2 years of age) do not show age-dependent loss of retinal ganglion cell (RGC) bodies when studied on retinal sections stained with H&amp;E and there is no visibly increased apoptosis in the retina (at 2 years of age) on TUNEL staining. In retinas from mice of 4-5 months of age proteolysis of Opal is normal and no statistically significant reduction in the average mitochondrial membrane potential is observed in the retina and brain. Quantitative RT-PCR on retinal samples does not indicate any differences in the expression of the six genes involved in the mitochondrial structure in mutant versus wild type mice. However, the observation of mitochondrial network in Mitotracker stained mouse embryonic fibroblasts (MEFs) at El3.5 demonstrates a higher incidence of fragmented mitochondria in MEFs taken from heterozygous mice, with a 15% increase in the number of opal +/- MEFs showing mitochondrial fragmentation (the average length of mitochondrial particles below 1 um), when compared to Opal +/- MEFs. However, their growth and survival after oxidative stress (with H2O2 and blue light) was not significantly affected when compared to the wild type control in a MTT assay. In conclusion, in Opal +/- mice, a reduction in the mitochondrial level of Opal caused a mild defect in mitochondrial morphology without any significant decline in those cellular functions investigated.

To date, it appears that many studies on dyslexia and its visual correlates are concentrated on children and there are only a few studies examining adult groups with dyslexia. This PhD introduces new knowledge about an adult population (university students) with dyslexia and those dyslexics who diagnosed with Meares-Irlen syndrome, compared to adults with normal reading abilities. Given that a common support strategy at undergraduate level is the provision of extra time in examinations, studies will focus on the effects of fatigue on binocular instability and ocular dominance amongst these cohorts.

The eye lens consists of epithelial cells, fibre cells and an outer capsule. The epithelium plays a crucial role in maintaining lens growth by continuous cell proliferation and differentiation into fibre cells throughout life. Many studies make or support the assumption that cell organisation within the epithelia of different mammalian lenses follows a common plan, while this has not been studied in detail. To better understand this and how it is associated with the development of posterior capsule opacification (PCO) in the human capsular bag after cataract surgery, I studied some basic cell characteristics in five kinds of mammalian lenses and in human donor capsular bags. The apoptotic cell number was very low in the lens epithelium. Cell density, height, cross-sectional area and volume were different in the three zones of the epithelium, and changed with age in the human lens epithelium. The majority of the cells in the peripheral capsular bag retained their polygonal morphology and were as a single layer. Cell proliferation was mainly restricted to the germinative zone (GZ) in the normal lenses and capsular bags. The proliferation index decreased with age in the human lens epithelium. FGF-2 could initiate cell proliferation by activating the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway. An FGF-2 gradient was detected in the inner surface of the bovine lens capsule and its level was statistically higher at the equator where cell proliferation and differentiation occurred. Cell proliferation, cell apoptosis and cell density and size in each zone were all consistent in the young lenses from bovine, mice, rats, rabbits and humans. This suggests that a single model may explain cell organisation in the mammalian lens epithelium and age will be one of its important parameters. Moreover, destroying the residual cell organisation in the peripheral capsular bags might prevent PCO.

Experiments were undertaken on prism adaptation in humans. Two treatment conditions were used. The restricted, where only localising movements of the arm were allowed and the free situation, where the subject was free to walk about. In the first situation: a) Adaptation takes place in effect at the level of the position sensors of the used joint. This is a change in felt limb position. b) Movement of the joint is a prerequisite condition. c) The sensory channel feeding in the error information is a passive instrument. d) Adaptation does not affect automatic movements: these take place without using information about joint position. In the second situation: a) Adaptation takes place in the positioning system of the eye; i.e., a change in the appreciated eye position. b) This form of adaptation takes place when the limbs are inspected, with or without repeated voluntary positioning movements of the eye. Immobility of the limbs favours this type of adaptation, but it will occur when gross limb movements are taking place.

Diabetes is a chronic disease affecting over 2% of the population in the UK [1]. Long-term complications of diabetes can affect many different systems of the body including the retina of the eye. In the retina, diabetes can lead to a disease called diabetic retinopathy, one of the leading causes of blindness in the working population of industrialised countries. The risk of visual loss from diabetic retinopathy can be reduced if treatment is given at the onset of sight-threatening retinopathy. To detect early indicators of the disease, the UK National Screening Committee have recommended that diabetic patients should receive annual screening by digital colour fundal photography [2]. Manually grading retinal images is a subjective and costly process requiring highly skilled staff. This thesis describes an automated diagnostic system based oil image processing and neural network techniques, which analyses digital fundus images so that early signs of sight threatening retinopathy can be identified. Within retinal analysis this research has concentrated on the development of four algorithms: optic nerve head segmentation, lesion segmentation, image quality assessment and vessel width measurements. This research amalgamated these four algorithms with two existing techniques to form an integrated diagnostic system. The diagnostic system when used as a 'pre-filtering' tool successfully reduced the number of images requiring human grading by 74.3%: this was achieved by identifying and excluding images without sight threatening maculopathy from manual screening.

Diabetes is an increasing problem worldwide and is placing increasing strain on the healthcare system. It often goes undiagnosed for many years until complications occur. Identifying undiagnosed disease presents a challenge to all healthcare professionals. In the UK, screening has traditionally been the role of general practitioners, although other professionals such as pharmacists have recently become involved. Optometrists may also be in a good position to carry out screening tests themselves. Their role in screening for diabetes has not been previously investigated. The first part of the thesis takes a qualitative approach to explore optometrists’ perceptions, attitudes and beliefs about diabetes and screening for the disease. It demonstrated that if certain barriers, such as cost and training, can be overcome, some optometrists are willing to carry out screening tests. It also raises issues regarding their professional roles and their relationship with other healthcare providers. The second part of the thesis describes the development and implementation of a screening scheme using random capillary blood glucose (rCBG) tests. Over three-quarters of eligible adults participated in the screening. We found that around one third (318) of those had a rCBG level requiring further investigation. Half of these people reported attending their GP and receiving further investigation. 16 (5%) were subsequently diagnosed with either diabetes or pre-diabetes. Those who participated in the screening programme found the test procedure to be comfortable, convenient and would recommend it to others. Analyses of strategies to identify those most at risk who would benefit from screening suggest that offering rCBG tests to those who are aged over 40 years with either a BMI of 25kg/m2 or more, or a family history of diabetes or both, would be effective for detection purposes. This research confirmed the feasibility of testing for diabetes in optometry practices and opens the door for another, PCT-based, study. This novel approach has never been tried before.

Since adaptive optics was first used to correct the monochromatic aberrations of the eye over a decade ago there has been considerable interest in correcting the ocular aberrations beyond defocus and astigmatism. In order to understand the prospective benefits of correcting these higher-order aberrations it is important to study their effect on visual performance. From a clinical perspective it is important to know how different types of aberration can affect visual performance so that wavefront measurements can be better understood. Visual performance is determined by a combination of optical and neural factors. It is important to consider how degradations in the optical quality of the eye can impact the neural processes involved in visual tasks such as object recognition. In this thesis we present a study of the effects of three types of aberration, defocus, coma and secondary astigmatism, on letter recognition and reading performance. In the course of this work we also characterise the repeatability of the Zywave aberrometer, which we used to measure our subjects' ocular wavefronts. We use stimuli that have these aberrations applied in their rendering to examine the differences between these aberrations and how they differ with respect to the visual task. We find that secondary astigmatism causes the largest impairment to both letter recognition and reading performance, followed by defocus. Coma causes comparatively smaller degradations to performance but its effect is different depending on the visual task. We can predict the reduction in performance based on a simple cross-correlation model of letter confusability. The relationship between these predictions and the experimental results are the same for all three aberrations, in the case of single letter recognition. In reading however, the relationship is different for coma. We suggest that coma causes lateral masking effects and may additionally disrupt the planning of eye movements. Coma slows reading, but does not specifically impair word identification whereas defocus and secondary astigmatism do. We attribute disruptions in word identification to the dramatic effects defocus and secondary astigmatism have on the form of a letter.

Background: Horizontal OKN is widely investigated and it is accepted that there is no horizontal OKN asymmetry in healthy adults. Vertical OKN is less well investigated and the direction of vertical OKN asymmetry is unclear. Aims: To investigate vertical OKN asymmetry in healthy individuals under of variety of different experimental conditions comparing: (i) the performance of look versus stare OKN, the effects of (ii) stimulus velocity, (iii) luminance profile, (iv) stimulus size and shape, and (v) distance on vertical OKN responses. The effect of neurological disease on OKN asymmetry in the form of Parkinson's disease was also investigated. Methods: OKN responses were recorded in healthy adult volunteers under a variety of experimental conditions including: (i) working distances of 33cm, lm, 1.2m and 2.5m (ii) sinusoidal and square wave OKN targets (iii) different target sizes ranging in size from 22.4°x28.9° to 65°x 55° (iv) contrasts of 50% to 100% and (v) target velocities of 20°/s and 40°/s investigating 'look and 'stare' OKN response. Stare OKN responses were also compared in subjects with Parkinson's disease and age-matched controls. All data was recorded using an infrared video pupil tracker. Result: No clear vertical OKN asymmetry was seen in normal adult subjects although the degree and direction of vertical OKN asymmetry remained relatively consistent for an individual under different stimulus conditions. Of all stimulus parameters target size had the greatest effect on vertical OKN asymmetry. Stare OKN was sensitive to distance for stimuli moving in the downwards direction. Parkinson's disease patients also had greatly reduced OKN responses for stimuli moving in the downward direction. Discussion: We found sensitivity of 'stare' OKN responses during downward stimulation to both target distance and the effects of Parkinson's disease. It is possible that this is related to the function of OKN during navigation, which is under cerebellar control.