The outcome of higher order aberrations (HOAs) prior to, and following, age-related cataract extraction and intra-ocular lens (IOL) implantation was explored using placido disc skiaoscopy aberrometry. Ninety-nine individuals (median age 73.0, IQR 67.0, 80.5) underwent comprehensive ophthalmic examination including contrast sensitivity, endothelial cell imaging and aberrometry (Nidek OPD ARK-10000) at approximately 4 weeks pre-operatively (median 3.9, IQR 2.9, 4.8) 10 weeks (median 7.1, IQR 5.64, 11.71) (67 individuals) and 80 weeks (median 85.1, IQR 80.0, 89.6) (41 individuals) post-operatively. Linear relationships between thirteen demographical, functional and structural variables and each of three components, Total (TC), Corneal (CC) and Internal (IC), for each of eight HOAs, were separately explored, using Analysis of Variance, for each examination and for the pre- and post-operative differences, respectively. The TC and IC of all HOAs decreased post-operatively (p≤68%). Preoperatively, the TC and IC of the Total HOA decreased as the spherical equivalent (SE) became less negative (both p<0.001, R2=0.56 and 0.53). Both components of the Total HOA also decreased as the difference in SE between baseline and each follow-up became less negative (all p≤0.008, R2=0.45-0.61); the magnitude of the reduction varied between IOL type (p≤0.008). The IC of the Tilt, T.Sph and HiAstig HOAs increased with increase in severity of posterior subcapsular (p=0.018), of cortical (p=0.013) and of combined nuclear colour and cortical cataract (p=0.003), respectively. The relationship between cataract type and severity and reduction in post-operative HOA was not statistically significant at either follow-up examination. Slight associations, presumably due to post-operative corneal oedema, were present between increase in CCs of five HOAs and decreasing endothelial cell density at the first follow-up, only, (all p≤0.030, R2=0.09-0.14). Pre-operative TCs and ICs were larger, respectively, than those of 22 individuals with ‘less severe’ cataract and post-operatively than those of 49 individuals with clear media, obtained from retrospective data.

The objective of the research is to provide the clinician with a simple system for making quantitative measurements that is comparable to the services of a skilled orthoptist. As many optometrists do not possess the necessary equipment for making such assessments, this technology would significantly enhance their referral capabilities. Reviews of the tests involved and instruments available are detailed in Chapter II and III. Chapter IV presents the various validation experiments carried out on the Tobii X120 eye tracker, concentrating on technical specifications such as, linearity range, optimum measurement distance and setup (with and without chin rest). We also investigated the effect of wearing different types of lens materials and pupil size measurements on the eye tracker system. We established the inter-examiner agreement of cover test measurements on groups of non-strabismic and strabismic subjects. This study, as detailed in Chapter V, involved collaboration with two clinical orthoptists. We found a good inter-examiner agreement for both the non-strabismic and strabismic cover tests. We further investigated the use of the eye tracker in providing more reliable findings for cover test measurements as compared to the conventional cover test (Chapter VI). Finally we extended the investigation to a number of different clinical subjects attending the Bristol Eye Hospital (Chapter VII) in order to evaluate our purpose-developed monocular calibration routine. Performing quantitative eye movement analysis will provide valuable additional information in any clinical investigation of patients with ophthalmological and/or neurological disorders, leading to greater precision in diagnosis. Traditional methods for the evaluation of oculomotor disorders rely on the diagnostic and therapeutic judgements by the examining clinicians and subjective responses from the patient. However, the use of currently available eye movement recording system will provide valuable alternatives for obtaining more objective and quantitative measurements.

The centrifugal visual system (CVS) is a feedback pathway of predominantly visual information from the brain to both eyes, but principally to the contralateral retina. The CVS is often considered to be something of a peculiarity, regarded as being specific to birds (Aves). Indeed, so-called ‘higher’ vertebrate species are assumed not to even possess such a centrifugal pathway when, in fact, an efferent projection to the retina has been conclusively demonstrated in all vertebrate groups (including humans). Perhaps this point of view reflects the lack of progress made in the elucidation of function in the bird, the dominant model for CVS research in the 120 years since being first described. In the series of experiments presented here, I have begun to investigate the role of the CVS in the modulation of eye growth. In addition, I have addressed a number of unknowns that exist regarding the midbrain connectivity of the CVS. In a series of four parallel lesion experiments, the centrifugal efferent pathway to the retina was unilaterally disrupted in post hatch chicks, raised under different developmental conditions. Under normal visual conditions but in the absence of centrifugal efferents, eyes contralateral to the lesion developed shorter eyes and moderate, relative hyperopia (long-sightedness). In contrast, under constant light conditions, ipsilateral eyes became significantly shorter than fellow (i.e. contralateral) eyes. Compensation for, and recovery from, plus and minus lens-imposed defocus in contralateral eyes was largely unaffected. Centrifugal efferents emanate from two distinct midbrain populations: the isthmo-optic nucleus (ION) and the surrounding scattered cells within the ectopic area (EA). From experiments using pathway tracing techniques, I have demonstrated that, unlike cells of the ION, EA cells do not receive input from primary visual areas. In addition I present evidence for a possible ‘cross-talk’ pathway between centrifugal cells on either side of the midbrain, and discuss its potential involvement in the normally symmetrical eye growth.

The studies described in this thesis aim to assess the importance of normal colour vision in visually demanding, colour-related tasks that are often safety-critical and aim to improve our understanding of how congenital deficiencies can affect the processing of colour signals and the corresponding changes in visual performance. The first study compares the colour vision requirements within different professional environments. 519 subjects were tested: 141 normal trichromats, 268 deutans and 110 protans. All subjects carried out the Ishihara 38-plate test, the CAD test and the Nagel anomaloscope, and sub-populations were examined with the AO-HRR plates, the Farnsworth D15, the City University test (2nd Ed.), the Holmes-Wright type A and B lanterns. Inconsistencies of outcome amongst the various tests and potential alternative practices are discussed. The second study focuses on understanding the discrepancies in performance observed on lantern tests when the subject’s task is to report the colour of small signal lights presented against a dark background field. These conditions were simulated using a psychophysical luminance pedestal technique. Variations in the measurement of chromatic sensitivity over the visual field, as well as the detection of targets where colours are combined with luminance contrasts, are discussed and explanations considered with regard to underlying retinal physiology. The last study investigates the use of colour signals in ATC (air traffic control) applications. The work carried out addresses current failings in acceptance criteria for applicants, and provides alternative methods of assessing suitability. The chromatic discrimination thresholds of normal trichromats and colour deficient subjects were related to performance on a set of visual search tasks selected to be more representative of typical colour usage in large field visual displays. Display parameters under which the performance of colour deficient observers could be comparable to that of normal trichromats are examined with regard to updating occupational acceptance criteria.

Conventional imaging devices only capture a part of the total information carried by the light. A new generation of imaging devices, plenoptic systems, use an array of micro lenses to codify the light coming from an object into a four dimensional function called the light field. The final image is then obtained after post processing computations on the light field. In this work plenoptic imaging devices are analysed using a wave optics approach. A platform to simulate light propagating under the Fresnel approximation in a generic optical system was developed in MATLAB. An optical system can be modelled as the composition of two basic operators: the free space propagation and the lens. The first one was implemented developing an original method derived from the angular spectrum of plane waves theory of propagation. The second was implemented using a phase mask. The code was developed to optimize the signal to noise ratio and the computational time. Two different configurations of plenoptic imaging systems were simulated. The first is the plenoptic 1.0 configuration. The general theory of plenoptic 1.0 and the post processing algorithms presented in the literature were verified using the simulation platform. The effects of diffraction were also evaluated and an original refocusing method is presented. For the second configuration, plenoptic 2.0, a full study of the optical resolution has been made and a detailed analysis of the effects of diffraction is presented. The results achieved with the simulations have been used to design a working prototype of a plenoptic microscope. This novel wave optics approach enables us to quantify for the first time in the literature the effects of diffraction on this class of devices. In plenoptic 1.0 diffraction is a source of noise due to the crosstalk between neighbouring lenslets. In plenoptic 2.0 systems the optical resolution is directly proportional to the magnification of the lenslet array. A small magnification leads to a high directional sampling but at the same time to a loss of optical resolution. The finite dimensions of the lenslets together with the wave nature of light produce a physical limit to the amount of information that can be achieved sampling the optical fields with those kind of devices.

A brief review of the literature on hemispheric differences is initially presented with special emphasis on the process-oriented theory which suggests that the left hemisphere (LH) processes analytically and the right hemisphere (RH) holistically. The purpose of the thesis was to test the analytic(LH)/ holistic (RH) theory. The main technique used involved a matching task ("Same-Different") with tachistoscopic presentations with male and female groups of right-handed subjects In addition, three experiments were run involving simple reaction time responses. The stimuli employed to test the theory were Stroop-type visual patterns (letters and arrows) comprising elements at both global and local levels. In Experiment 1 (global letter matching), the LH generated a Stroop effect revealing analytic mechanisms while the RH showed no such effect revealing holistic strategies. In Experiment 2 (local letter matching) and in Experiments 3, 4, 5and 6 (global and local letter matching) the results showed that both hemispheres can process analytically when "forced". Some results indicated the possibility of certain variables affecting the RH's analytic processing more than the LH's suggesting that some differences in efficiency of analytic processing between the two hemispheres may exist. Experiments 7--13 tested the theory with different and lessverbally codable material (arrows) than the letter stimuli. The results in the local matching experiment confirmed the finding that both hemispheres when "forced", can apply analytic strategies. The results of the other arrow experiments suggested that it is possible in certain experimental conditions to demonstrate holistic processing not only by the RH but also by the LH. Alternative interpretations were however possible. It is concluded that the dichotomy of the LH processing analytically and the RH holistically is not maintained.

Static automated perimetry of the central 30˚ is the most often used visual field test in glaucoma patients. Short test durations are achieved by focusing on a central region, which constitutes ~20% of the visual field. However, ignoring the periphery may sacrifice information on how patients are affected functionally. Peripheral vision is important for guiding attention, balance and mobility. An efficient standard automated examination for the peripheral visual field has not been established yet. This thesis aims to lay groundwork for the development of such a test. I introduce a kinetic automated test, which estimates an isopter with three repeated presentations per meridian. I ask whether measuring a peripheral isopter adds information to central visual field test results, investigate retest reliability and evaluate the efficiency of test procedures with repeated presentations through computer simulations. Moreover, I investigate how visual field thresholds obtained with static and kinetic stimuli relate to each other and examine the influence of stimulus sizes III and V on static threshold estimates. I also investigate the relationship between response variability and contrast sensitivity in the peripheral visual field. Based on the results, I suggest using repeated presentations in automated kinetic tests. I demonstrate that data driven computer simulations are useful for the development of efficient automated kinetic perimetry. The frequency-of-seeing results suggest that response variability to static stimuli in the far periphery is lower than suggested by previous data (Henson et al., 2000). This is relevant to future computer simulations of peripheral visual field tests with static automated perimetry. As a future avenue for examining the visual field periphery I propose a combined static kinetic automated visual field test, which combines a peripheral isopter as a region of interest with static stimuli inside this region. In a separate investigation, I examine the influence of visual field damage on reading performance and evaluate the relationship between reading performance and eye movements, using a within-patient between-eye study design in glaucoma patients with asymmetrical visual field loss. Between-eye reading performance was affected by visual field loss and co-occurred with specific eye movement patterns. The within-patient between-eye design appeared to be useful for investigating the relationship between visual field loss and functional disability.

In this study a possible role for RPE cells as local antigen presenting cells in immune inflammatory eye disease was investigated. In contrast to observations in the rat model of EAU however, Class II positive RPE cells were never observed in vivo in the guinea pig model of EAU but responses of RPE cells in vitro implied that these cells may have an immunoregulatory role in retinal autoimmunity. The T cell mediated nature of EAU was studied in the guinea pig model. The phenotype of inflammatory cells present in developing lesions was examined. Earliest choroidal infiltrates appeared to be Th cells, but in established choroidal foci of inflammatory cells and in early retinal lesions, where rod outer segment (ROS) lysis was occurring, the presence of a Pan T-ve, Tc/s+ve population of putative effector cells was identified. In endstage lesions B cells became the predominant cell type, and may act as suppressor cells in this species. Infiltrating inflammatory cells and capillary endothelial cells expressed Class I and Class II antigens but RPE and Muller cells did not. Cyclosporin A (CsA) therapy prevented vitreal inflammation and there was a marked reduction of Class II antigen expression despite choroidal infiltrates of Tc/s. Delayed type hypersensitivity (DTH) skin reactions to retinal antigen were also profoundly suppressed by CsA.

There exists a newly discovered, well defined, acellular, strong layer, termed pre-Descemets layer or Dua’s layer (PDL), in the cornea just anterior to the Descemets membrane. This, with the Descemets membrane, separates along the last row of keratocytes in most cases of deep anterior lamellar keratoplasty with the big bubble technique. Recognition of this layer has considerable impact on lamellar corneal surgery, understanding of posterior corneal biomechanics and posterior corneal pathology, such as descemetocele, acute hydrops and pre-Descemets dystrophies. The aim of this work was to understand the dynamics of big bubble formation in the context of the known architecture of the cornea stroma, ascertain how type 1 (air between deep stroma and PDL), type 2 (air between PDL and Descemets membrane) and mixed bubbles (combination of type 1 and type 2) form and measure the pressure and volume of air required to produce big bubbles in vitro, including the intra-bubble pressure and volume for the different types of big bubbles. We also aimed to characterise the optical coherence tomography characteristics of the different layers in the wall of the big bubbles to help surgeons identify bubbles and understand the structures seen by intra-operative OCT. Finally we evaluated the endothelial cell density and viability in tissue samples obtained for Descemets membrane endothelial keratoplasty (DMEK) and pre-Descemets endothelial keratoplasty (PDEK) by the pneumodissection technique. Air was injected in 145 corneo-scleral samples, which were unsuitable for transplantation. Samples were obtained in organ culture medium from the UK eye banks and transferred to balanced salt solution ready for injection. Different types of big bubble formed were ascertained. Air pressure and volume required to create the big bubble in simulated deep anterior lamellar keratoplasty were measured. It was found that PDL could withstand a high pressure before bursting at around 700 mm of Hg. Accurate measurements of type-2 big bubble proved challenging. The volume of the type-1 BB was fairly consistent at 0.1ml. The movement of air injected in the corneal stroma was studied from the point of exit from the needle tip to complete aeration of the stroma and formation of a BB. This was video recorded and analysed. A very consistent pattern of air movement was observed. The initial movement was predominantly radial from the needle tip to the limbus, then circular in a clock-wise and counter clock-wise direction circumferentially along the limbus, then centripetally to fill the stroma. All type 1 BB started in the centre as multiple small bubbles which coalesced to form a BB. Almost all type 2 BB started at the periphery near the limbus. Ultrastructural examination of the point of commencement of type 2 BB revealed the presence of clusters of fenestrations, which most likely allow air to escape from the otherwise impervious PDL to access the plane between PDL and DM. This was a novel discovery and explained how type 2 BB formed and why they almost always start at the periphery. The consistent pattern of passage of air was in concordance with the known microarchitecture of the central and peripheral corneal stroma. Optical coherence tomography (OCT) characteristics of different types of big bubbles were studied. Samples obtained from the UK eye banks were scanned with Fourier-domain (FD-OCT), while that obtained from Canada eye bank were scanned with Time-domain (TD-OCT). A special clamp was used to affix the corneo-scleral sample on the OCT table with its posterior surface face the machine and mounted on artificial anterior chamber. It was found that FD-OCT could demonstrate type 1 BB wall as two parallel, double contour, hyper-reflective lines with hypo-reflective space in between. It also revealed that in type-2 BB, the posterior wall showed a parallel, double-contour curved hyper-reflective line with a dark space in between. This probably corresponds to the banded and non-banded zones of DM. Dua’s layer presents as a single hyper-reflective line. In TD-OCT, the posterior wall of type-1 and type-2 BB showed a single hyper-reflective curved line rather than the double-contour line. This finding will help cornea surgeons to identify and interpret different layers of big bubble intra-operatively with high resolution OCT devices. Endothelial cell density of PDEK and DMEK tissue were calculated. Endothelial cells were counted using light microscope before pneumodissection. Air was then injected to ascertain the creation of type-1 and type-2 BB. Tissue was then harvested by trephination and endothelial cell density of both types were calculated again. It was found that the corneal endothelial cell count in PEDK tissue preparation is no worse, if not slightly better than, in DMEK tissue prepared by pneumodissection. Therefore, PDEK preparation represents a viable graft preparation technique.

Dry age-related macular degeneration (AMD) is a common eye condition, which causes progressive loss of central vision; there is currently no treatment. The live studies presented in this thesis aimed to explore different aspects of everyday visual function and the experience of living with dry AMD. In the first study, a systematic review of the literature surrounding quality of life and "real-world" visual ability in AMD was conducted. Several domains of everyday life affected by AMD were identified; these had been investigated using a wide variety of study designs. However, only 4% of studies meeting inclusion criteria specifically investigated individuals with dry AMD. In the second and third studies, people (>60 years, logMAR binocular visual acuity of 0.7 or better) categorised with varying severities of dry AMD performed two previously validated computer-based real-world visual tasks. Comparisons for both tasks were made against a 90% normative limit for the outcome measures established in age-related peers with healthy vision. In a search task, participants were instructed to find items within digital photographs of everyday indoor and outdoor scenes. Sixty-one percent of participants with dry AMD, (including all of those with late dry AMD) exceeded the 90% normative limits for average search time; this was statistically significant (Fisher's exact test, p < 0.0001). In a face recognition task, participants completed a modified version of the Cambridge Face Memory Test. Percentage of correctly identified faces was used as an outcome measure. Five (17%) participants with dry AMD scored worse than the 90% limit (Fisher's exact test, p=0.46); four of these had fovea-involving geographic atrophy. In the fourth study, volunteers with dry AMD described their visual symptoms in an interview and were asked to comment on the realism of a photograph typically used to simulate vision in AMD. Interview transcripts underwent content analysis. The most frequently used visual symptom was blur (n=13) followed by missing part/s (n=10) and distortion (n=7). Seventy-six percent (95% confidence interval 53-92%) of the participants rejected the realism of a popular image often used to portray the visual symptoms of AMD. In a fifth study, a novel test measuring mobility anxiety was introduced. Participants were shown a series of short movies of navigation through real-world mobility scenarios and were asked to press on a button during scenes which would cause them anxiety or discomfort. Pressure on the button was recorded throughout the test and this was used as an outcome measure. People with intermediate and late AMD applied more pressure to the button, on average, than those with early and no AMD (Kruskal-Wallis test, p=0.04). Situations involving negotiating stairs were identified as particularly problematic. To conclude, these studies spotlight the problems people with dry AMD have with visual tasks. In addition, the tests described in this thesis may have potential to be used as patient- based outcome measures for clinical trials for future treatments for dry AMD. Moreover, findings reported in this thesis may help clinicians with patient management and expectations, and should inform future patient, public and professional education about dry AMD.