No description available.

Glaucoma is a leading cause of visual impairment and, if untreated, irreversible blindness. Perimetry is the clinical tool for assessing the functional ‘seeing’ part of the field of view (visual field) and is widely used in the detection and clinical monitoring of glaucoma. These measurements rely on a psychophysical response making them inherently variable. This measurement noise can disguise both disease pathology and progression. The work described in this thesis aims to improve the quality of perimetric measurements. The platform for this is the Moorfields Motion Displacement Test (MMDT), a perimetric test that uses unconventional test stimuli and can be delivered on an ordinary computer monitor. Specifically, this thesis describes efforts to develop novel, mathematically derived, test algorithms, designed to be used with the MMDT. The performance of these new testing methods is assessed using pilot studies involving patients and visually healthy people, computer simulation and interim results from a large prospective clinical study. One of these test algorithms, the Enhanced Suprathreshold Testing Algorithm [ESTA] provides shorter test duration, making it attractive for case-finding and screening for glaucoma, without seemingly negatively affecting diagnostic precision, and has become patented technology. Another bespoke test algorithm (Weighted Binary Search; WEBS) provides a threshold test for the MMDT. The thesis also describes a study examining the resistance of several newer clinical perimetric instruments to the optical artefact of stray light that might be caused by media opacity. This is clinically important because cataract and degraded optical media is a leading cause of false-referral for glaucoma. This work, being the first of its kind, indicates that the MMDT has greater resilience to simulated effects of media opacity compared with other clinically used devices.

When the light reflected from an object differs in spectral composition to the surrounding background these spectral differences are reflected in the excitation levels produced in each class of photoreceptor. The ability to see colours and to notice small colour differences is strongly affected by both the spectral composition and luminance level of the adapting light. Knowledge of the limits of colour detection is important in setting safety standards and guidelines in visually demanding workplaces, as varying conditions of illumination and chromatic adaptation are often encountered in different working environments. It is therefore of both fundamental and practical interest to be able to predict accurately how a human observer’s chromatic detection performance changes with both light level and chromatic adaptation. The Colour Assessment and Diagnosis (CAD) test was employed to measure colour detection threshold ellipses under different states of chromatic adaptation and background light levels. The advantage of this new technique is that it isolates the use of colour signals by embedding the isoluminant chromatic stimulus in dynamic luminance noise. These measured threshold variations were analysed in terms of changes in L-, Mand S-cone excitation levels required for threshold in different colour directions. Models based on the measured chromatic threshold data are proposed that are capable of reconstructing entire detection ellipses. These models were based on experiments where observers had colour thresholds measured around a series of different chromatic adaptation points, over a range of light levels (typically from 0.3 to 31 cd m-2), and additionally away from the adaptation point. The findings reveal the independent adaptation states of individual cone classes on measured thresholds, i.e., the threshold in a given cone class depends only on the signal produced by the background in that cone class and is independent of the adaptation state of the other cone classes and hence independent of chromaticity and light level. The effect of adapting different areas of the peripheral retina when thresholds are measured foveally was also investigated. No long range retinal interactions were observed. The results show that the adaptation state of the periphery has no effect on colour detection thresholds made in central vision. Variations in L-, M- and S-cone contrasts curves were simulated to assess the influence that detection ellipse size and ellipse orientation have on them. This revealed a correlation between the L-cone contrast curve gradient and the corresponding ellipse orientation. This was additionally shown to correlate with the central 2.8° mean value of macular pigment optical density, hence providing a new method of estimating macular pigment level from colour detection ellipses. Steady state pupil sizes were analysed with the rod and cone excitations that produced them. These data indicate that when chromatically adapted, the steady state pupil size correlates strongest with the S-cone signal, and is independent of the actual chromaticity and luminance levels involved. Cone signal-to-noise ratios were extracted from repeated threshold measurements for a series of colour directions. Analysis of these revealed the existence of a constant signal-to-noise ratios over the full range of colour directions tested relative to a whitish background. The results show that as the cone contrast level increases in a particular cone class so does the associated noise.

The Contrast Acuity Assessment (CAA) test was developed to assess the minimum spatial vision requirements for commercial pilots. The goal of the CAA test was for it to be sensitive to retinal image degradation in subjects who had undergone excimer laser refractive surgery. Increased aberrations and scattered light or abnormal processing of visual information in the retina and/or the visual pathway are the main causes of retinal image degradation. The purpose of this study was to further investigate the effect of aberrations, scatter and other parameters on the CAA test under photopic and mesopic conditions. This could help to provide explanations for previous CAA test results. The effect of contrast, stimulus onset time, pupil size and crowding on the CAA test was examined. This was in order to try to provide explanations for the decline in Landolt ring gap acuity over the central 5 degrees, as observed in previous CAA test results, which had shown a foveal dip to occur under photopic and mesopic conditions. Contrast Sensitivity was measured on eight subjects using 6 and 3 mm artificial pupils using the City University Contrast Sensitivity Test. A significant trend of decreasing contrast sensitivity with increased pupil size occurred for the middle and lower spatial frequencies (1.2 and 6.1 cpd), but not for the highest 19.1 cpd spatial frequency. The effects of using high contrast (125%) rather than low contrast (24%) CAA test targets were investigated, in combination with the use of artificial pupils of 6 mm and 3 mm. We concluded that low contrast could play a role in producing a foveal dip under photopic and mesopic conditions. The effect of crowding and stimulus onset time on the CAA Test was examined on 3 subjects, by reducing the contrast of the fixation guides under mesopic and photopic conditions and increasing stimulus onset time. This gave inconclusive results. No significant conclusions were drawn concerning the effect of crowding or stimulus onset time on the CAA foveal dip. The effect of aberrations on normal subjects on the photopic and mesopic CAA test was examined, to determine whether they may have influenced the foveal dip. 14 subjects were tested with natural pupils, under photopic conditions and 10 subjects, were tested under mesopic conditions. A Shack Hartmann aberrometer was used to take wavefront aberration measurements. No significant regressions were found between aberrations and foveal dip. We concluded that aberrations were probably not the cause of the foveal dip. Q value lenses consisting of Q = -2, Q = -1, Q = 0, Q = +1 and Q = +1.5 contact lenses were tested on subjects with natural pupils, to determine whether the CAA test could pick up larger non-physiological changes in aberrations. Large changes in visual performance were observed. Z (4,0) spherical aberration versus central CAA gap acuity was found to produce a significant quadratic regression under mesopic conditions. Seidel coma and Seidel astigmatism were also found to produce significant linear regressions. under photopic conditions. Scatter was measured in 4 subjects, using 6 mm and 3 mm artificial pupils, to determine whether scatter would increase with the larger pupil size. Linear regressions of scatter k’ versus foveal dip gave results which were not statistically significant. Scatter was measured for 3 subjects using the 5 different Q value contact lenses, to see if the Q values affected the scatter. The results were not statistically significant. The differences in scatter produced were found to be far less than the increase of scatter found in two subjects with pathological conditions. We concluded that scatter played an insignificant role in producing the foveal dip or changing visual performance with the use of Q value contact lenses. The project produced a systematic investigation of the parameters affecting the CAA test. A statistically significant association, described by a quadratic regression curve, exists between CAA mesopic gap acuity and Z (4,0) spherical aberration.

In 2009 approximately 480,000 people were affected by COAG in England. Furthermore, glaucoma sufferers and suspects are responsible for over one million glaucoma-related outpatient visits annually. Community optometrists make over 95% of suspect COAG referrals, identifying suspects through opportunistic case-finding. Optometrists’ case-finding is largely based on a triad of tests: optic nerve head assessment, tonometry, and visual fields. There has been little research into optometrists’ COAG case-finding strategies. Chapter 2 reports on a national survey regarding COAG case-finding methodologies and referral criteria. Survey response validity was confirmed by comparing these with a national sample of referral letters. UK optometrists are well-equipped to detect COAG. Optometrist’s skills and scope of practice in the detection of glaucoma have evolved since the last national survey in the late 1980’s. The level of funding and nature of the GOS contract in England limits development of effective services for glaucoma detection. For comparison, the survey was also performed in the Netherlands. Dutch optometrists own fewer automated field screeners but more goniolenses and pachymeters, and are more likely to use binocular indirect ophthalmoscopy than UK optometrists. Chapter 3 describes the development of a competency framework for optometrists with a specialist interest in glaucoma utilising Delphi methodology. The Delphi technique is a robust method for gaining autonomous expert opinion. This approach has led to the development of an accepted national competency framework for optometrists with a special interest in glaucoma. Chapter 4 evaluated the impact of a postgraduate educational intervention on aspects of glaucoma detection. The intervention increased awareness of disc changes in glaucoma, but was less effective for clinical decision- aking and for improving performance in the Discus program for disc assessment. The traditional didactic teaching style is unsuited for training optometrists in the clinical competencies required for glaucoma detection and management. Chapter 5 is a unifying summary of preceding chapters and contains recommendations for future research.

No description available.

The cover test is probably the most widely used clinical test of oculomotor status. It is surprising therefore, that there has been only one previous study which has attempted to provide a quantitative analysis of the eye movements during the test. There is also a dearth of information concerning the relationship between eye movements during the cover test and symptomatology and the correlation between cover test results and the outcome of other tests of binocular function. For the investigations described in this thesis, apparatus was developed to provide precise measurements of eye movements during a computer-controlled cover test, with subjects fixating a distant (3.4m) and near (0.4m) target. In the first study, this apparatus was employed to assess a group of asymptomatic emmetropes aged between 18 and 35 years (n = 100). The pattern of eye movements recorded was more complex than is often assumed. Eye movements during dissociation followed various patterns, with some subjects reaching a position of equilibrium within a few seconds while 20% had not reached a stable position at the end of the 10 s occlusion period. It was concluded that the 'standard' procedure of occluding an eye during the cover test for only about 2s is not adequate. The mean phoria after 10 s occlusion was 0.000 for distance fixation and -1.38° (exo) for near fixation. The pattern of eye movements during the recovery phase consisted of a variety of saccadic and vergence movements. There was a statistical difference between exophores and esophores for frequencies of initiating saccades and vergence eye movements (p < 0.001) with esophores more commonly commencing recovery with a saccade and exophores with a vergence eye movement. Recovery movements were often associated with movements of the "fixating" eye. There was a poor correlation between phoria amplitude and recovery time. In the second study, the relationship between the nature of eye movements during the cover test and the results of other common tests of binocular function was investigated. There was very little correlation between any aspect of the eye movements and the results of the other tests, or indeed between any of the tests of binocular function. In the third study, a group of symptomatic individuals were characterised using the automated cover test and a battery of other tests of binocular function. In the fourth study, the association between eye movement characteristics during the cover test and symptomatology was investigated. Results gave some support to the long-held view that a slow multi-stage recovery tends to be associated with a symptomatic binocular vision problem. In the fifth study, various aspects of binocular function were monitored throughout the course of orthoptic therapy. Not all subjects responded to treatment and none of the clinical tests assessed were found to be good discriminators of subjects who were likely to benefit. While several aspects of binocular function were found to parallel the amelioration of symptoms, the results were very variable.

This investigation involved a number of related studies with the principal aim of assessing the variability in chromatic sensitivity in "normal" trichromats and colour deficient observers. An important outcome was the development of a new method for accurate and efficient measurement of chromatic sensitivity and the establishment of reliable statistical limits that describe the distribution of redgreen(RG) and yellow-blue (YB) chromatic sensitivity in normal trichromats. Chromatic sensitivity was assessed using a computer-based psychophysical procedure that employs spatiotemporal luminance contrast (LC) masking techniques to isolate the use of colour signals. The colour-defined stimuli were buried in dynamic LC noise and moved diagonally across a square. The subject's task is to indicate one of the four possible directions of stimulus motion by pressing the corresponding response button. The Colour Assessment and Diagnosis (CAD) test was optimised for stimulus size and background luminance level to provide an efficient measure RG and YB chromatic sensitivity. Colour detection thresholds are assessed along 16 directions in chromaticity space, selected to yield maximum information on RG and YB chromatic sensitivity loss and to distinguish between deutan and protan deficiencies. The CAD test was used to measure chromatic discrimination thresholds in 472 observers. The results made it possible to evaluate the screening and diagnostic efficiency of the CAD test in comparison with a number of established clinical colour vision tests, e.g., Nagel anomaloscope and Ishihara pseudoisochromatic plates. The specificity and sensitivity of the CAD test versus the Nagel anomaloscope (223 subjects) was found to be 100% and 97.5%, respectively. The diagnostic agreement with respect to the Nagel anomaloscope was 0.99; only two subjects showed inconsistent classification deficiency. Chromatic thresholds measured in normal trichromats were also examined and the variability amongst normal colour vision was investigated. The data obtained were used to establish the statistical limits for the standard normal observer on the CAD test. A template based on these limits was generated and provides an efficient way of separating accurately colour deficient from normal trichromats. The high specificity found is consistent with the correct detection of minimal colour deficiencies that sometimes go undetected in other colour vision tests. Molecular genetic analysis was also carried out in a small group of subjects with unusual colour deficiencies in an attempt to understand the genotype-phenotype relationship between predicted and observed colour vision losses. A comparison of genetic results from DNA sequencing and chromatic detection thresholds measured on the CAD test suggests that the separation of 30 nm between peak sensitivity of L and M normal photoreceptor pigments is not an absolute requirement for an observer to exhibit normal colour vision as assessed with conventional colour vision tests. The macular pigment (MP) optical density was also measured in 23 subjects selected for their higher than normal levels of pigment as a result of their participation in a carotenoid supplementation trial. This pre-receptoral filter absorbs light preferentially in the short wavelength region of the visible spectrum and has been shown to affect colour matches. Contrary to expectations, the findings of this investigation showed no correlation between YB thresholds and MP optical density levels. A model that explains this finding was produced confirming the observed experimental findings. In addition, the model also predicts a small improvement in RG chromatic discrimination sensitivity with increased MP optical density in the eye.

Optical Coherence Tomography (OCT) is a non-invasive volumetric imaging technique that offers micron scale resolution over several millimetres of depth penetration in tissue. The aim of the project was to develop Full Field Swept Source OCT (FFSSOCT), charting the specifications of the system throughout and drawing comparisons with available Fourier domain OCT (FDOCT) systems. A super luminescent diode (SLD) light source was tuned to different optical frequencies using an acousto-optical tunable filter. The successive optical frequencies were distributed across the sample in parallel and the sequential interference spectra were recorded with a high speed digital camera. Using a 5mW optical source at 850nm, 70dB sensitivity was ultimately achieved in a single five second acquisition, improving the original performance by 5dB and increasing acquisition and processing time significantly. Ex vivo retinal images of rat and tree shrew were recorded with multiple layers visible. All software was custom written in Labview, improving the user interface and processing time over the existing Matlab code. To enhance the performance of the system, the camera was subsequently upgraded from 15 to 45% quantum efficiency and from 250k to 1.3M pixels. The light source was also upgraded to 20mW. The software was improved with spectral processing and dispersion compensation. 85dB sensitivity was ultimately achieved. Further ex vivo retinal images were taken, showing comparative image quality to those of the same retinal samples recorded with FDOCT. Further attempts to increase the system performance were limited by internal reflections and interfering surfaces within the FFSSOCT design leading to saturation of the digital camera. In vivo imaging was attempted using software based phase jitter compensation. Improvement could be seen with simple reflecting structures.

The experiments which comprise this thesis focused on structure-function relationships in two distinct collagen-rich connective tissues of the eye, the cornea and the trabecular meshwork. The cornea is the transparent tissue that covers the front of the eye and has the ability to transmit and refract light. Corneal transparency is the result of the unique organisation of collagen fibrils in the corneal stroma matrix, of which sulphated proteoglycans are key regulators, owing to the presumed importance of the sulfation pattern of corneal proteoglycans. The trabecular meshwork is the sponge-like tissue located around the cornea through which the bulk of the aqueous humor flows towards the juxtacanalicular tissue and the inner wall of Schlemm’s canal to exit the eye and control intraocular pressure. First part of the current research examined the chemical composition and sulphur speciation during corneal embryogenesis in order to elucidate important changes in the biochemical signature of the corneal matrix associated with the acquisition of transparency. It also investigated the content and distribution of distinct sulphur species through the depth of the mature corneal stroma and assessed biochemical-functional relationships that ultimate render tissue transparency. The research also studied the three-dimensional ultrastructure of the human trabecular meshwork, particularly the ultrastructure of the juxtacanalicular tissue that lies adjacent to the inner wall of Schlemm’s canal and the three-dimensional assembly of collagen type VI in the trabecular meshwork itself. X-ray fluorescence microscopy revealed key differences in the chemical composition of the cornea of the developing chick. In particular, the chemical signature of phosphorus, chlorine, sulphur, potassium and calcium were observably different during the developmental period from day 12 to day 16. S k-edge x-ray near edge structure spectroscopy showed that the main sulphur species present in the embryonic cornea were thiols, organic monosulfides, ester sulphate and inorganic sulphate. The chemical signature of these sulphur species was also noticeably different during embryonic corneal development. The changes in the chemical signature of phosphorus with development are believed to underline changes in the presumptive keratocyte population within the embryonic corneal stroma. Chlorine, potassium and calcium are important elements involved in the regulation and balance of the net negative or positive charge of the embryonic cornea and may influence the interactions of corneal matrix molecules. The changes in the sulphur speciation character amongst different developmental corneas are associated with changes in the sulphation status of corneal proteoglycans which play a fundamental role in governing tissue structure and function, and thus transparency. With regards to the sulphur speciation across the depth of the mature corneal stroma, it was found that there is an inconsistency in the sulphur content and distribution throughout the depth of the tissue, from the stromal region closest to the epithelium against the deeper stromal regions near the endothelium. The heterogeneity of the sulphur species in the most anterior part of the mature corneal stroma, at the interface with the Bowman’s layer supports the view that the differentiation and the transition between these two corneal layers is not very abrupt. The rest of the mature corneal stroma depth does not show any differences regarding its content in the sulphur-containing compounds indicating that the distribution and sulfation status of the corneal glycosaminoglycans have very little impact on the overall sulfur speciation. The three-dimensional ultrastructure of the human trabecular meshwork in large volumes and at high resolution identified giant vacuoles in the endothelial cell layer of the inner wall of Schlemm’s canal and these were grouped into four categories based on whether they formed pores, basal and apical, or not. Interestingly, the distribution of these vacuoles was found to be non-uniform. It was discovered that the juxtacanalicular tissue was not homogenous with respect to the proportion of the electron lucent, matrix free spaces throughout the tissue’s depth away from the inner wall of Schlemm’s canal. Three-dimensional reconstructions of collagen type VI in the trabecular meshwork showed that there is no structural regularity in the organisation of type VI collagen assemblies, or their association with sulphated proteoglycans, suggesting a role in aqueous humor outflow. This data allow us to propose a model of aqueous humor outflow and how this is funneled through the juxtacanalicular tissue towards the lumen of Sclemm’s canal.