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.

No description available.

Retinopathy of prematurity (ROP) is a potentially blinding retinal disorder that affects small prematurely born infants which results from the combination of the immature retina and the high level of oxygen (hyperoxia) needed to keep these infants alive. A rat model of oxygen induced retinopathy (OIR) was developed to better understand what occurs in premature infants that are exposed to postnatal hyperoxia and previous studies have demonstrated that this model bears a striking resemblance to the human form of ROP, at least in its vascular component. The purpose of this study was to investigate beyond the retinal vasculature in order to better understand the functional [electroretinogram (ERG)] and cytoarchitectural (histology and immunohistochemistry) manifestations of this disease. / While structural and functional consequences of OIR in the albino rat had previously been evaluated in mature rats (at postnatal days 30 and 60, for example), the sequence of events leading up to these changes could only be inferred. Consequently, the purpose of our first study was to further characterize the early manifestations of this disease process, namely: 1- to evaluate changes in retinal vasculature throughout exposure to hyperoxia and, 2- to examine how early after the cessation of oxygen exposure we can demonstrate changes in retinal structure and function. Findings suggest that while the vascular growth process could repair itself while still subjected to a hyperoxic environment (from P0-12 and P0-14, for example), irreversible changes in retinal ultrastructure and function could still be evidenced, and are documented immediately following the cessation of the hyperoxic regimen (Dorfman et al., 2008). / It has been suggested that free radicals may be the source of the pathologic effects described above. Given that trolox C, a water-soluble analogue of vitamin E, was previously shown to limit the vasculopathy component of OIR, the aim of our next study was to determine whether it could prevent the functional and structural consequences of OIR. While trolox C could limit the damage intrinsic to the rat model of OIR, it could not entirely prevent it from occurring. This suggests that either OIR is not solely caused by the action of free radicals or that trolox C is inadequate in treating all aspects of OIR (Dorfman et al., 2006). / We next sought to compare our findings using trolox C with those obtained using the pigmented Long Evans (LE) rat in which melanin is thought to play an antioxidant role. Our results show that melanin did not exert the predicted protective effect on retinal structure and function, where LE rats were affected earlier on and more drastically than albino Sprague Dawley rats following hyperoxic exposure (Dorfman et al., 2009). Specific markers for rod and cone bipolar cells (PKC-α and recoverin, respectively), amacrine cells (parvalbumin) and horizontal cells (calbindin) reveal that OIR is primarily an inner retinal disorder, the earliest consequences of which include cell death in the inner retina (TUNEL staining) and synaptic retraction in the OPL (synaptophysin) (Dorfman et al., in preparation). / Collectively, our results suggest that the rat model of OIR is not only useful for studying retinal vasculature, but can also be used to further elucidate the functional and structural sequelae that likely resemble the human form of ROP. Our ability to demonstrate persistant functional and cytoarchitectural damage despite vascular repair would suggest the importance of examining beyond the fundus in ROP patients, should these features also apply to humans. ROP is one of several types of proliferative retinopathies characterized by retinal ischemia followed by abnormal vessel growth. Studies such as these will undoubtedly be instrumental in a better understanding of these types of retinopathies and in the derivation of new therapeutic avenues aimed at controlling them. / La rétinopathie du prématuré (RDP) est une maladie rétinienne qui potentiellement aboutie à la cécité des enfants de faible poids nés prématurément et qui est causée par la combinaison de l'immaturité de la rétine et du niveau élevé d'oxygène (hyperoxie) essentiel pour garder ces nouveau-nés en vie. Afin de mieux saisir l'effet de l'hyperoxie postnatale chez ces bébés prématurés, un modèle animal de rétinopathie induit par l'oxygène (RIO) a été développé chez le rat et a démontré une forte ressemblance à la forme humaine de la RDP, du moins dans sa composante vasculaire. Notre but était d'examiner au-delà de la vascularisation rétinienne afin de mieux comprendre les manifestations fonctionnelles [électrorétinogramme (ERG)] et cytoarchitecturelles (histologie et immunohistochimie) de cette maladie. / L'évaluation antérieure de la fonction et de la structure rétinienne chez les rats albinos matures (par exemple à 30 et 60 jours postnatals) de la RIO a uniquement permis de déduire la chaîne d'évènements menant à ces changements. Par conséquent, la première étude consistait à caractériser les signes hâtifs de la RIO, pour: 1 - évaluer la vascularisation rétinienne durant l'exposition et, 2 - savoir quand, au plus tôt, après l'exposition les changements de structure et de fonction peuvent être observés. Les résultats suggèrent que la croissance vasculaire pourrait se restaurer durant le stress hyperoxique (expositions de P0-12 et de P0-14, par exemple), malgré la présence des changements irréversibles de l'ultrastructure rétinienne et sa fonction survenant immédiatement après la fin du régime hyperoxique (Dorfman et al., 2008). / Les radicaux libres ont été suggérés d'être à l'origine des effets pathologiques décrits ci-dessus. Étant donné que trolox C, un analogue hydrosoluble de la vitamine E, a été démontré de limiter la composante vasculaire de la RIO, le but de l'étude suivante était de voir s'il pouvait aussi prévenir les séquelles fonctionnelles et structurelles. Nos résultats montrent que trolox C représente une alternative thérapeutique valide limitant les dommages, mais il n'empêche pas la totalité des dégâts rétiniens causés par l'oxygène. Ceci suggère que la RIO n'est pas juste provoquée par l'action des radicaux libres ou que le trolox C est inadéquat pour traiter tous les aspects de la RIO (Dorfman et al., 2006). / Nous avons ensuite comparé nos résultats de trolox C à ceux obtenus avec le rat pigmenté Long Evans (LE) dans lequel la mélanine est présumée de jouer un rôle antioxydant. Nos données montrent que la mélanine n'exerce pas l'effet protecteur prévu sur la structure et la fonction de la RIO, où les rats LE ont été affectés plus tôt et plus gravement que les rats albinos Sprague Dawley suivant l'exposition à l'oxygène (Dorfman et al., 2009). Le marquage spécifique pour les cellules bipolaires de bâtonnet et de cône (PKC-α et recoverin, respectivement), les cellules amacrine (parvalbumine) et les cellules horizontales (calbindine) indiquent que la RIO est une maladie de la rétine interne définie par une mort cellulaire à ce niveau (TUNEL) et par la rétraction synaptique dans la couche plexiforme externe (synaptophsine) (Dorfman et al., manuscrit en préparation). / En conclusion, nos résultats suggèrent que le modèle de rat de la RIO est non seulement utile pour étudier la vascularisation rétinienne, mais peut aussi être employé pour élucider les conséquences fonctionnelles et structurelles pouvant ressembler au modèle humain de la RDP. Notre capacité de démontrer les dégâts fonctionnels et cytoarchitecturels persistants en dépit de la réparation vasculaire suggérerait l'importance de l'examen approfondi chez les patients avec la RDP. La RDP est une forme des nombreuses rétinopathies prolifératives. Ces genres d'études seront certainement utiles pour une meilleure caractérisation de ces types de rétinopathies et dans la création de nouvelles méthodes thérapeutiques visant à mieux les contrôler.

It has been proposed that CD4+ T cells and cell-mediated immunity play a central role in corneal allograft rejection. Two subsets of CD4+ T cells, Th1 and Th2 cells, are known to cross-regulate each other through their cytokine pattern and the immune response might be directed predominantly in one or the other direction. As such, it has been hypothesized here that predominant Th1 type immune response could lead to corneal allograft rejection, and that previous inflamed corneal beds (high-risk eyes) might augment the Th1 response and thus accelerate the graft rejection. / Reverse transcription of mRNA followed by polymerase chain reaction amplification was used to determine the relative gene expression in ocular tissues (cornea and iris/ciliary body) obtained from syngeneic grafts, low- and high-risk allografts. Compared with the syngeneic grafts, mRNA analysis of the low- and high-risk allografts showed a significantly decreasing expression pattern for the Th3 cytokine TGF-beta2, an early peak followed by a decline in the Th2 cytokines IL-4 and IL-10 expression, and a progressively increasing expression of the Th1 cytokines IL-2 and IFN-gamma and the proinflammatory cytokines IL-1beta and TNF-alpha, which paralleled the course of graft rejection. Prevascularization of the recipient eye (high-risk) significantly accelerated the rejection of corneal allografts and the mRNA levels of the Th1 cytokines IL-2 and IFN-gamma and proinflammatory cytokines IL-1beta and TNF-alpha in high-risk allografts were significantly higher and peaked faster than that in low-risk allografts. / In vivo gene transfer using plasmid DNA encoding cytokines is an attractive alternative to modulate the Th1 inflammatory reaction and immune response. This has led to the hypothesis that transferring the gene encoding Th2 cytokine IL-10 into the recipient could prevent or reduce the subsequent corneal allograft rejection through the suppression of Th1-mediated alloimmune response. / Intramuscular injection with in vivo electroporation of IL-10 plasmid DNA was administered at one week before and at one week after corneal transplantation. Corneal allograft survival was significantly prolonged and the rejection rate was significantly reduced after gene therapy with IL-10 plasmid DNA, compared with that in control groups treated with the empty plasmid vector. In IL-10 treated rats, the mRNA expression for the Th1 cytokines IL-2 and IFN-gamma was depressed, and the IL-10 mRNA expression was significantly increased. However, graft survival was not permanent. (Abstract shortened by UMI.)

Traditionally, human visual sensitivity changes in luminance and chromatic contrast, collectively termed photometric changes, have been measured using simple laboratory stimuli such as disks or gratings. The results of experiments using such stimuli have generally been accounted for in terms of relatively low-level mechanisms such as quasi-linear filters in the visual cortex. Therefore, one might not expect the higher-order structure of natural scenes to influence sensitivity to uniform photometric changes. On the other hand, it is believed that the visual system is optimized for analyzing visual information in natural scenes, which leads to the alternative hypothesis that the unique structure of natural scenes will influence sensitivity to photometric changes. We tested between these two hypotheses by comparing sensitivity to uniform photometric changes in natural scenes with sensitivity to uniform photometric changes in the same scenes with the structure removed through phase scrambling. Sensitivity was found to be higher in the natural compared to phase-scrambled scenes. Additional experiments ruled out the possibility that the higher sensitivity in the natural scenes was due to one's familiarity with their colors, or that the lower sensitivity in the phase-scrambled scenes was due to the increase in color variability introduced by phase scrambling. In another series of experiments sensitivity to uniform photometric transformations in both natural and phase-scrambled scene was measured in dichoptic image-pairs that were transformed in equal and opposite directions. The results suggested that the superiority in sensitivity in natural scenes resulted from mechanisms operating at or after the point of binocular combination. Finally we considered whether the superiority in sensitivity in natural compared to phase-scrambled scenes was underpinned by one of the defining characteristics of natural scenes: the presence of uniform areas separated by edges. This require / Le rôle de la structure des images naturelles dans la sensibilité visuelle aux changements photométriques uniformes Chez l'être humain, les changements dans la sensibilité visuelle aux contrastes chromatiques et achromatiques, appelés changements photométriques, sont traditionnellement mesurés à l'aide de stimuli simples tels que des disques ou des réseaux de bars. Les résultats de ces études reposent généralement sur des mécanismes de bas-niveau tels que les filtres quasi-linéaires du cortex visuel, qui prédisent que la structure des scènes naturelles ne devrait pas influencer la sensibilité aux changements photométriques. D'un autre coté a été émise l'hypothèse selon laquelle le système visuel est optimisé pour l'analyse de l'information présente dans les scènes naturelles, ce qui suggère que la structure unique des scènes naturelles pourrait influencer la sensibilité aux changements photométriques. Nous avons donc testé ces deux hypothèses en comparant la sensibilité aux changements photométriques uniformes pour des scènes naturelles dont la structure est soit restée intacte, soit éliminée par l'intermédiaire d'un brouillage de leur information de phase. Les résultats de cette étude démontrent que la sensibilité est plus grande pour les scènes naturelles intactes que leurs versions ‘brouillées'. Des expériences complémentaires excluent la possibilité que la sensibilité plus élevée pour les scènes naturelles soit due à une familiarisation à leurs couleurs, ou la possibilité que la sensibilité plus faible pour leurs versions brouillées soit due à l'augmentation de la variabilité chromatique induite par le brouillage de phase. Dans une autre série d'expériences, la sensibilité aux changements photométriques uniformes pour les scènes intactes et brouillées a été mesurée pour des paires d'images présentées dichoptiquement et pour lesquelles les changements photométriques ont été appliqu