Glaucoma is a progressive disease of the optic nerve that can result in visual impairment and in tum inhibit performance on everyday visual tasks. Three connected experimental studies described in this thesis primarily aim to investigate the performance of people with glaucoma on a computer-based task of reading whilst simultaneously recording eye movements. Fifty four patients with bilateral glaucoma and 40 age-similar people with normal vision took part in the experiments. The first study measured change in reading speed when letter contrast is reduced. Results showed that average reduction in reading speed caused by a difference in letter contrast between 100% and 20% is significantly more apparent in patients when compared with age-related people with normal vision and similar cognitive/reading ability (p=0.01). Furthermore, patients more adversely affected by a contrast change were generally those with more severe visual field (VF) defects, poorer contrast sensitivity and poorer visual acuity. A second study explored the relationship between specific locations of the binocular VF and measured reading speed. Results suggested that damage to the inferior left region of the binocular VF was most strongly associated with the reading speed of the patient group. It is possible that this is the VF region used when locating a new line of text and it may be of clinical importance to preserve sensitivity in this area of the VF. The third study used a subset of patients with advanced glaucomatous (N=IS) VF defects to explore the relationship between eye movements and reading speed. Three eye movement measures were explored namely. text saturation (difference between the first and last fixation on lines of text), perceptual span (total number of letters read per number of saccades) and saccadic frequency (total number of saccades made to read a single word presented in isolation in a bespoke lexical decision task). Some, but not all, patients with advanced VF defects read slower than controls but differences in eye movements accounted for much of this variability. These patients also saturated text more during reading when compared to controls (p=O.004) which may explain previously-reported difficulties with sustained reading in glaucoma. In conclusion, principal findings from the studies described in this thesis show, for the first time, that reading speed in patients with glaucoma is particularly affected by changes in text contrast and specific regions of the VF are associated with impaired reading speed. Moreover, eye movement analysis may provide a window into the functional deficits associated with reading in glaucoma

Glaucoma is a chronic and progressive disease of the optic nerve that can lead to irreversible loss of function in the visual field (VF). Whilst much research tends to focus on areas such as the development of measures for diagnosing, monitoring and treating glaucoma, less is known about how this visual degradation manifests itself as the person goes about their lives outside of the clinic. This thesis describes five studies which examine different aspects relating to the experience of disability and the quality of life (QoL) of people with glaucoma. In study I, a systematic literature review revealed that only approximately I % of research studies in glaucoma relate to investigations of the effects of the disease on the patient's QoL, and the proportion of studies relating to QoL in glaucoma was less than in many other disabling chronic diseases, including age related macular degeneration (AMD). More than 80% of the studies identified were found to involve the use of questionnaires; a method that although useful for gaining insight into the patient's own perceptions of their condition, is subject to bias. More objective performance-based measurements of functioning may also be useful for determining the impact of glaucoma on the person's life. This approach was taken in study 2, which investigated the performance of 54 patients with varying levels of glaucomatous VF loss on a face recognition (FR) task compared with 41 people with normal vision. It was found that patients with more advanced VF defects performed significantly worse on average than patients with early and moderate defects, and controls (F=3.2; p<0.05). Multiple regression analysis revealed that contrast sensitivity (CS) measurements were important for FR. The importance of contrast for performance on the FR task was thus investigated further in study 3, which examined the effects of image contrast manipulations on the performance of 40 visually healthy participants on a modified version of the FR task. There were no statistically significant effects across contrast conditions, suggesting difficulties relating to face image contrast alone might not fully explain poorer performance. Study 4 investigated whether eye movements may underlie the likelihood of a patient experiencing task difficulties. It was found that, for patients with significant 10° VF defects, those who made larger eye movements also appeared to be better performers (rho=0.60; p=O.OOI). These effects were not found in people with healthy vision, which could imply that some patients use eye movements to 'adapt' to their condition. A final exploratory study aimed to examine patient perceptions of their VF defect, by interviewing patients about their condition. Patients appeared to differ in terms of their level of awareness of their defect, despite all having advanced VF loss. These findings may suggest the potential of further research investigating the link between conscious awareness of one's defect and the employment of adaptive strategies in glaucoma for overcoming VF loss.

No description available.

No description available.

Glaucoma is a group of disorders with a broad range of clinical and histopathological manifestations. This condition presents itself in many different ways and with distinct shared characteristics that include optic neuropathy due to optic nerve head damage (cupping) and visual field dysfunction with or without presence of increased intraocular pressure (lOP). Glaucoma is the leading cause of irreversible blindness, which afflicts nearly 67 million people worldwide. It is considered the second most frequent cause of bilateral blindness, affecting 6.7 million people worldwide. By 2020, glaucoma is anticipated to affect 79.6 million people, increasing the number of bilaterally blind individuals due to glaucoma to 11.1 million. This thesis aimed to provide new insights into the molecular genetics of adult-onset Primary Open Angle Glaucoma (POAG) and a paediatric form of Primary Congenital Glaucoma (PCG). In the first portion of this work, the GLC1B locus on chromosome 2pl1.2-qI2.2 was investigated using extensive linkage and saturation mapping in order to reduce the region and to select potential candidate genes for screening 9 previously linked families. Genomic Convergence and Proteomic Streamlining methods were used to select and prioritise the most likely candidate genes. The prioritisation was based on tissue expression, bioinformatics, microarray data, as well as assessment of their protein- encoded functions. This investigation leads to the hypothesis that there may actually be two areas of interest for the GLCl B locus, one on the p arm and the other on the q arm of chromosome 2. Since at least three other independent studies shared a common overlapping area on the q arm of chromosome 2, single nucleotide polymorphisms (SNPs) from each of the genes within this common region were selected for a regional gene-specific association study. After genotyping our linked-GLC1B POAG families, sporadic cases and other matched control subjects, the genes that showed strong association were selected and screened for mutations. After direct sequencing of these genes, 62 DNA alterations (known and novel intronic and exonic variants) were observed and their disease-causing nature was carefully investigated. In conclusion, the GLC1B locus has been significantly reduced to a region of approximately 6.66-Mb. A total of 10 candidate genes were selected, individually sequenced and ultimately excluded as being involved in the aetiology of a group of GLC1B-linked POAG families. Further work is necessary to identify the defective gene(s) at the GLC1B locus. In the second portion of this thesis, the GLC3C locus on chromosome 14q24.3- q31.1, the study aimed to prioritise genes using similar methods to the strategies previously used to identify candidate genes within the GLC1B locus. These included Genomic Convergence, Proteomic Streamlining and the information from other linked families within the region. A total of 7 regional candidate genes were selected, sequenced and excluded as being involved in the aetiology of our GLC3C-linked family. Altogether, 80 DNA alterations (known and novel intronic and exonic variants) were observed in the sequenced genes and their disease-causing nature was carefully investigated. In addition, to the screening of the above-mentioned GLC3C candidate genes, a newly described PCG-causing gene, LTBP2, was fully sequenced and excluded in our GLC3C-linked family. Additionally, a total of 94 familial and sporadic PCG and 96 matched-control subjects were fully sequenced for the entire 36-coding exons of the LTBP2 gene. Only two heterozygous DNA alterations were identified in 2 PCG individuals, which were absent in 96 normal control subjects. Since no homozygous mutations were observed, further investigation is required to determine the disease- causing nature of these two DNA alterations. Therefore, this study was unable to replicate previously described mutations in the PCG subjects from Pakistan and Iran. Likewise, at least one other study of American PCG cases did not find any gene mutations in the LTBP2 gene, thus further confirming the observation of this study. As this gene is implicated in diseases with multiple clinical presentations, further investigation is necessary to determine the overall role that LTBP2 plays in the isolated PCG phenotype as well as in identifying the causative gene(s) within the GLC3C locus.

No description available.

There were four principal sections to the work: 1. Investigation of ocular and systemic vascular risk factors in POAG. The principal findings of this work were: a). Glaucoma patients exhibit an anticipatory reaction to the physical stress, similar to subjects at risk for cardiovascular diseases; a blunted BP response and a reduction in ONH blood flow in response to cold provocation was also recorded. b). Silent myocardial ischaemic episodes occurred during peaks in systemic BP and HR. c). Independent of a positive history for cardiovascular diseases, patients suffering from POAG demonstrate a blunt circadian rhythm of the ANS. 2. Assessment of the relationship between vascular and systemic vascular risk factors in GON. The principal findings of this work were: a). POAG patients demonstrate a high sympathetic tonus over a 24-h period. b). POAG patients with lower OBF demonstrate both 24-h systemic BP and HRV abnormalities. c). OBF alterations observed in some glaucoma patients could be either primary or secondary to systemic haemodynamic disturbances and not a consequence of ONH damage. 3. Assessment of the level of systemic anti-oxidant defence in POAG patients. The principal finding of this work was: Patients suffering from POAG demonstrated significantly lower GSH and t-GSH levels than normal controls. 4. Investigation of the effect of treatment with latanoprost 0.005% on visual function and OBF. The findings of this work were: a). Treatment with latanoprost 0.005% resulted in a significant decrease in IOP and increase in OPP. VF damage progression has also been stopped. b). Treatment with latanoprost 0.005% resulted in a significant increase in the OBF parameters measured at the ONH and peripapillary retina levels. Finally, the importance of a clear protocol for managing new POAG cases is highlighted and a clinical conduit is proposed.

Chronic Open Angle Glaucoma (COAG) refers to a chronic progressive condition that is characterised by damage to the optic nerve, resulting in peripheral visual loss that can progress to involve the fovea and central vision; subsequently causing blindness. COAG is reported to have a poor level of adherence to treatment due to its asymptomatic nature. In this study, a Glaucoma Expert Patient Programme (GEPP) demonstrated new ways of improving patients' experience and adherence to COAG treatment. The research has employed an Information-Motivation-8ehavioural Skills Model to understand the association between knowledge, motivation and behavioural skills in an attempt to improve adherence amongst recently diagnosed patients. Patient participation was at the heart of every component of the study. In this research, four Expert Patients were trained and supported to deliver an educational programme (termed the GEPP) to 25 recently diagnosed patients with COAG (Intervention Group) and then a comparison was made to 25 participants (Control Group) that were also recently diagnosed with COAG but did not receive the educational programme. Three pre and post educational programme validated questionnaires were used to measure patients' knowledge, satisfaction and adherence at baseline and then discern changes at 1 month and 6 months follow up to the GEPP intervention. Staff (N = 10), Expert Patient (N = 4), Intervention Group (N=10) and Control Group (N=10) semi-structured interviews were also conducted to obtain deeper insight into their experiences of engaging in the programme. Data analysis indicated IMPROVING AWARENESS was the main theme that emerged supported by three subthemes: knowledge, satisfaction and adherence. This research has taken the Patient-Patient relationship to a higher level. It is viewed that the Expert Patients' experience is crucial and valuable to improving the experience, knowledge and adherence of newly diagnosed patients with COAG. The GEPP delineated in this study provided insight regarding individuals' life experiences of living with and managing chronic complex glaucoma. Implications for practice relate to the development of tailored educational programmes. This research contributed new knowledge to improving the adherence practices of glaucoma patients. It also demonstrated the value of Expert Patients' experience and their contribution to assisting newly diagnosed patients in self-managing their COAG.

Background: Glaucoma is a chronic, progressive eye disease and the second cause of blindness in the world. To measure the patients’ perspective in randomised controlled trials (RCTs), patient-reported outcome measures (PROMs) are increasingly being used. However, the use of PROMs in glaucoma trials is low suggesting there may be a reluctance to use PROMs. Objectives: To explore three methodological challenges of using PROMs in RCTs in glaucoma: 1) PROM selection; 2) characterising glaucoma severity; and 3) interpreting PROM scores in terms of minimal important difference (MID). Methods: Vision PROMs used in glaucoma studies were identified and content validated using a systematic review approach and categorised by a new PROM taxonomy. Existing visual field staging systems (VFSSs) based on standard automated perimetry were systematically identified and quality assessed with a new tool developed for this review using a consensus method. The performance of four high quality visual field staging systems were evaluated and referenced against an experienced ophthalmologist in a diagnostic test accuracy study. A pilot study using the social comparison approach was undertaken to test the feasibility of an anchor-based approach in determining the MID of a vision PROM in a glaucoma population. Results: Thirty-three vision PROMs were identified and categorised, according to content into impairment, disability, status and satisfaction measures. Twenty-three VFSSs were identified but evaluation of quality assessment, particularly performance, was affected by poor VFSS reporting. The diagnostic accuracy study demonstrated suboptimal performance of the four highest quality staging systems. The pilot study to determine the MID for a vision PROM found the social comparison method to be a feasible approach in a glaucoma population. Conclusion: This thesis demonstrated how to select a PROM and identified difficulties with characterising glaucoma severity. Future research needs include development of robust methods for characterising glaucoma severity and full scale evaluation of MIDs in PROMs in glaucoma.

The present work deals with the fluidic analysis of a glaucoma drainage device, which involves modelling, three-dimensional computational fluid dynamic work of a rather difficult optimization problem involving strong nonlinearities. The results have been accompanied by in-vitro experiments in order to evaluate and finally demonstrate the power of computational analysis. The results of this work have been transferred and are applicable right away to the development of a commercial novel medical device. This study can be considered as applied and technological research. The deliverables include a user-friendly graphical interface designed in MATLAB and also drawings of the proposed optimized geometry. In the following chapters are presented the literature review about the disease, the mathematical background and the available materials and methods that are used as well. The main idea behind this report was that the study should be reproducible at any time. Therefore, special attention was paid to the way of presenting the settings of all the software that was used. The last two chapters present the results and the discussion respectively. / Η παρούσα εργασία πραγματεύεται τη λειτουργία μιας συσκευής παροχέτευσης ενδοφθάλμιου υγρού. Πιο συγκεκριμένα περιλαμβάνει τρισδιάστατη ρευστοδυναμική ανάλυση και ένα δύσκολο πρόβλημα βελτιστοποίησης που εμπεριέχει ισχυρές μη-γραμμικότητες. Τα αποτελέσματα της εργασίας έχουν μεταφερθεί και εφαρμόζονται μέσα στην ανάπτυξη μιας εμπορικής καινοτόμου ιατρικής συσκευής. Αυτή η εργασία εντάσσεται στο πλαίσιο της εφαρμοσμένης και τεχνολογικής έρευνας. Τα παραδοτέα της εργασίας περιλαμβάνουν μια φιλική διεπαφή προς το χρήστη που έχει αναπτυχθεί στο λογισμικό MATLAB και σχέδια της προτεινόμενης βελτιστοποιημένης γεωμετρίας. Στα ακόλουθα κεφάλαια γίνεται βιβλιογραφική ανασκόπηση περί του γλαυκώματος, παρουσιάζονται τα μαθηματικά μοντέλα που χρησιμοποιήθηκαν και επίσης τα μέσα και οι μέθοδοι. Ιδιαίτερη βαρύτητα κατά τη συγγραφή της παρούσας εργασίας δόθηκε στον τρόπο παρουσίασης των μεθόδων ώστε να είναι εύκολη η αναπαραγωγή του αποτελέσματος. Τα δύο τελευταία κεφάλαια της εργασίας παρουσιάζουν τα αποτελέσματα και τα συμπεράσματα αντίστοιχα.