A two-stage qualitative research strategy using semi-structured interviews was conducted with a convenience sample of 45 participants who lives with type 2 diabetes. In Stage One of the research, a qualitative study was conducted using semi-structured interviews with a purposive sample of 25 participants. Of these, 20 participants were diagnosed with type 2 diabetes, two participants were primary care physicians, two were ophthalmologists, and one was a retinal screener. People with diabetes were purposely recruited to fall into four groups with different grades of diabetic retinopathy. The aim of Stage One was to explore how people with type 2 diabetes perceive diabetic retinopathy risk, their understanding of risk information, and to appraise existing risk communication tools that have been used in other clinical settings. The data from Stage One was analysed and used to develop a risk communication tool designed to provide risk information about diabetic retinopathy and diabetic screening results to people with type 2 diabetes, which was then used in Stage Two. In Stage Two of this research, a total of twenty people with type 2 diabetes were recruited. Participants were divided into two groups based on their grade of diabetic retinopathy. Group one: 10 participants with no diabetic retinopathy (R0); Group two: 10 participants who had background diabetic retinopathy (R1). The aim of Stage Two was to i) appraise a newly developed risk communication tool that was developed to communicate risk information about diabetic retinopathy to people with type 2 diabetes, ii) to explore the influence of the new developed risk tool on risk perception and on diabetes self-care management, and iii) to establish a method(s) by which risk information about diabetic retinopathy can be effectively communicated to people with type 2 diabetes. All interviews were audio recorded and transcribed using a digital recording machine. Data was analysed using constructivist grounded theory approach.

Movement has an effect upon the perceived spatial position of moving objects, such that they are not perceived at their instantaneous spatial position. Vision scientists named this phenomenon motion-induced position shift (MIPS). The reason, neural loci, and the mechanisms causing the positional illusion have challenged scientists over the last century. Nowadays, many vehicles, such as cars, planes and submarines are equipped with onboard computers containing touchscreens. Active controls of those on-board computers require visuomotor-actions, which could be affected by perceptual illusions, but also require time, and attention. Hence, it is becoming more crucial to fully understand how the visual system generates visuomotor-guided actions, and how it copes with visual illusions. Human-machine interactions could be designed such that perceptual illusions would be 1) avoided, or 2) predicted, and considered in human actions, or such that 3) the user interacted with visuomotor actions that resisted visual illusions. One alternative to finger points towards on-board computers is saccadic eye movements. The saccadic system is very fast, and therefore, would not require as much time and attention as a finger point task towards the touch screen. Saccades are constantly facing the challenge of localising objects, which makes it interesting to study how they cope with visual illusions like the motion-induced position shift. The purpose of this thesis was to establish if the saccadic system was affected by the motion-induced position shift in the same manner as the perceptual system was affected. I confirmed that movement had an effect upon the perceived spatial position of moving objects in perception-tasks and in volitional saccades. A previous study showed that reflexive saccades resisted the illusion, indicating that they were more accurate than other visually guided actions. I replicated these results, but claimed that the results are not representative. As a consequence, there is no evidence that reflexive saccades do escape the visual illusion while volitional saccades do not.

The aim of this study was to investigate differential aspects of spatial vision in subjects presenting with macular degeneration and visual snow. Emphasis was placed on the effects of aging and/or ocular disease on binocular summation and the measurement of differences between the two eyes in a number of visual tasks. Accommodation performance was measured for both pre-presbyopic and presbyopic observers. The results showed no binocular advantage for either group for far or intermediate stimulus vergences. The effects of visual crowding upon visual acuity were tested using a Landolt C optotype with surrounding distractors. Binocular advantage was found to be higher along the line of sight and to decrease in the near periphery. The presence of distractors reduced visual resolution significantly at every eccentricity, with the effect becoming more pronounced in the periphery. The latter was observed for both monocular and binocular viewing conditions leading to the suggestion that the involvement of binocularly driven neurons may not be essential for visual crowding. The effects of healthy aging and ocular disease on spatial and chromatic vision were also investigated. It was found that stimulus presentation time in a gap acuity task affects visual acuity differently in patients with Age-related Macular Degeneration (AMD) when compared to normal subjects. The processing of briefly presented optotypes appears to be severely reduced in AMD patients. Visual performance was also investigated in patients who experience ‘visual snow’. While gap acuity at any stimulus duration and the strength of chromatic afterimages were found to be unaffected, involuntary pupil recovery following brief exposure to chromatic stimuli was found to be delayed in 3 of the 6 visual snow (VS) patients examined. The absence of a normal pupil recovery is consistent with abnormally slow signals that may also play a part in VS. The novel findings reported in this thesis suggest that advanced vision tests can be used to quantify the effects of normal aging and to detect and monitor the earliest changes in diseases of the eye.

There is little epidemiological information about cataract in children globally and thus a lack of evidence to guide policy related to childhood cataract. Early presentation for cataract surgery in children is an important first step for effective treatment. The overall aim of this research was to determine the age at childhood cataract surgery in India and to understand the barriers and enablers to accessing childhood cataract services in the region. A mixed methods approach was used. Quantitative data were obtained via a questionnaire in nine different eye hospitals in eight states in India. Qualitative data were collected from the perspectives of parents and carers and primary eye care providers using in-depth interviews and focus group discussions respectively and Theoretical Domains Framework (TDF) of behaviour change was used for analysis. A systematic review was conducted to estimate global prevalence of childhood cataract. This was estimated to be 1.14 /10000 overall, and 0.46 /10000 in low and lower middle income economies. The mean age at surgery for congenital cataract in India was 4 years and for developmental cataract it was 8 years, but these numbers varied significantly between the regions in the country. Delays to surgery occurred at recognition, when accessing the hospital and delayed surgery at the hospital. The barriers and enablers identified from the perspectives of the parents and carers suggest a need for behavioural change intervention to enhance health seeking behaviour in the communities. The findings suggest gaps in knowledge and awareness among the primary care team which should be further investigated and addressed. Based on these research findings several recommendations were identified and a preliminary recommended intervention strategy was developed to achieve behaviour changes with the aim of increasing early uptake of childhood cataract services in India.

Refractive errors such as myopia are the leading cause of reversible visual impairment worldwide with their prevalence rapidly increasing, resulting in greater burden on public health services. The aim of this series of investigations was to leverage the latest statistical methods and large-scale cohorts available in order to develop our understanding of the genetic determinants for the refractive error traits of spherical equivalent, corneal astigmatism and refractive astigmatism. Investigation of genetic variants on the X-chromosome, a region often neglected in genome-wide association studies (GWAS), identified four genes demonstrating association in a gene-based analysis of spherical equivalent for a cohort of teenagers. Meta-analysis of GWAS results for corneal astigmatism including European and Asian ancestry cohorts performed on behalf of the CREAM consortium successfully replicated the previously identified association near the PDGFRA gene (lead variant: rs7673984, odds ratio = 1.12, P = 5.55 × 10−9). The availability of data from the UK Biobank facilitated the largest GWAS for corneal and refractive astigmatism performed to date (N = 86,335 and 88,005 respectively). Here, GWAS for these traits identified four and two novel loci associated with corneal and refractive astigmatism respectively. Each of these loci had previously been associated with other ocular traits including myopia. Phenotypic variance explained by common genetic variants was relatively low for corneal and refractive astigmatism at ~6% and ~5% respectively, thus proposing a greater role for rare variants in explaining astigmatism variance due to genetics. Lastly, in order to link identified variants and genes functionally influenced in myopia development, several candidate myopia genes identified from a primate myopia model demonstrated enrichment with refractive error associated variants in human samples. Overall, the findings from these investigations are a starting point in guiding further research into the complex biological mechanisms underlying refractive error development.

Myopia, as a common ocular disorder, is caused by both genetic and environmental factors. Conventional genome-wide association studies (GWAS) in humans have limited power to detect myopia genes partly due to the complex interplay between genes and environment. Here, I performed a GWAS in a sample of chicks with form deprivation (FD) myopia, aiming to reduce environmental complexity and increase the statistical power to detect genetic variants that confer susceptibility to this environmentally-induced myopia phenotype. The degree of FD myopia was quantified by measuring the treatment-induced changes in axial length (∆AXL) and mean spherical equivalent (∆MSE). Body weight, sex, and batch were evaluated as potential confounding factors. To reduce costs, chicks in the phenotype extremes (lowest or highest ∆AXL, within each batch) were selected for genotyping. To identify genetic variants conferring susceptibility to myopia, GWA analyses for ∆AXL and ∆MSE were applied to the genotype data. After adjusting for confounding factors, genetic variant rs317386235, located between the genes PRKAR2B and PIK3CG exceeded the Bonferroni corrected significance threshold for ∆AXL. To complement the GWAS findings, an RNA sequencing transcriptomics analysis was performed, using retinal tissue from the treated and control eyes of chicks with high or low-susceptibility to myopia. This revealed 516 differentially-expressed genes, identified using a combination of three analysis tools. In order to discover more about the biological function underlying the GWAS and transcriptomics analysis results, pathway analyses were conducted. The pathway analysis implicated gene sets relating to circadian rhythms, extracellular matrix (ECM) and structural remodelling, energy generation, oxidative stress, glycometabolism and lipid metabolism.

Dry eye disease (DED), and especially work-related dry eye, has an increasing incidence, and is expected to become a significant public health problem, with the increasing age until retirement, and the effect of the modern, digital, working environment causing higher visual demands. The indoor environment and more demanding, eye-related tasks, are risks factors for the development of dry eye symptoms, leading to DED at these workplaces. The current management for diagnosed DED is strongly pharmaceutical-based, and research looking at solutions towards better functioning and well-being of DED patients is rare. There is also a lack of evidence about the role of healthcare professionals in DED management. A substantial proportion of office workers surveyed experienced mild/moderate dry eye symptoms, and that while these were experienced more at work than at home, they had a negative impact on daily activities at work and after work, interfering with their social life. There is a lack of in-depth knowledge in dry eye diagnosis and management in all primary healthcare professionals surveyed and education is needed in management of work-related dry eye; there is a need for a specialised DED optometrist, with a recognised qualification; inter-professional cooperation should be promoted through better communication pathways; OHPs and optometrists should work together at the association level to develop clinical care guidelines; and a chronic care pathway in DED should be developed as part of the Dutch Government healthcare reforms.

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the developed world. Whilst the pathogenesis is complex and not fully understood, changes to the choroidal vasculature in AMD have been demonstrated using histology. Advances in imaging technology, particularly long-wavelength optical coherence tomography (OCT), allow in vivo visualisation and investigation of this structure. The aim of this work is to determine whether changes to the choroidal vasculature are detectable in AMD using in vivo imaging. This was achieved through the evaluation of parameters for quantifying the structure, and the application of a machine learning approach to automated disease severity classification, based on choroidal appearance. Participants with early AMD (n=25), neovascular AMD (nAMD; n=25), and healthy controls (n=25) underwent imaging with a non-commercial long-wavelength (λc=1040 nm) OCT device. Subfoveal choroidal thickness, choroidal area, and luminal area were significantly lower in the nAMD group than the healthy and early AMD groups, whilst vessel ratio was significantly greater (P < 0.05 in all cases). There was no significant difference in visible vessel diameter, choroidal vascularity index, luminal area ratio, or luminal perimeter ratio between the groups. No significant differences were found between the healthy and early AMD groups for any of the eight vascular parameters assessed. Classification of the disease groups based on choroidal OCT images was demonstrated using machine learning techniques. Textural features within the images were extracted using Gabor filters, and K-nearest neighbour, support vector machine, and random forest classifiers were assessed for this classification task. Textural changes were most pronounced in late-stage disease, although attribution to pathology or pharmacological intervention (anti-VEGF treatment) was not possible. Changes were also discernible in the early AMD group, suggesting sensitivity of this approach to detecting vascular involvement in early disease. In conclusion, structural changes to the choroidal vasculature in AMD are detectable in vivo using OCT imaging, demonstrated with both manual and automated analysis techniques. Whilst changes were most prominent in late-stage disease, subtle structural changes in early AMD were identified with texture analysis, warranting further investigation to improve our understanding of choroidal involvement in the pathogenesis of early AMD.

The purpose of this thesis was to develop further the Learning Index in perimetry and examine how it performs in different groups, with different algorithms and investigate different procedures of calculation. The Learning Index calculated using concentric rings of visual field data, following the method of Olsson and colleagues (1997), facilitated in a MatLab environment. The used data included visual field assessment for 29 normal, 25 glaucoma and 25 ocular hypertensive individuals who followed perimetry for both eyes, for different strategies and for five consecutive visits once a week. Alternative methods to evaluate the LI were used like the glaucoma hemifield test pattern. The influence of the different strengths of a variety of filters was also used, filtering the perimeter outcome in order to disassociate learning effect from real defects. Mean and Median filters were also used, and dissimilar Adaptive filters as well, that seemed to be robust filters that could help to establish a more sensitive Learning Index. In automated perimetry the innovation of a Learning Index would consider and examine how individuals learn to perform better visual field tests during recurrent visits under different algorithms. The argument is if that Learning Index could allow clinicians performing visual field tests to administer their patients and control possible detected abnormality, after their first or second visual field test. In this way they will prevent development of the disease, confine patient’s fatigue and provide quality of life and simultaneously financial savings for the state and private health organizations. The carried out learning index calculations results were sufficiently encouraging for a next phase of a future index development and with likelihood in the future to be incorporated in automated perimeters algorithms.

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the developed world (Wong et al., 2014). The exact causes of AMD are unclear but hypoxia has been implicated (Stefánsson et al., 2011). If hypoxia has a role in the pathogenesis of AMD treatments that mitigate the effect of retinal hypoxia may slow disease progression. This thesis aimed to establish the impact of light therapy, as delivered using a light emitting mask, on the progression of AMD. A phase I/IIa randomised controlled trial was implemented in which 60 participants with early and intermediate AMD were allocated to the intervention or the untreated control group in a 1:1 ratio and monitored over 12 months. The ability of secondary outcome measures (including: rate of cone dark adaptation, 14Hz flicker threshold and chromatic thresholds) to identify the likely risk of progression from early and intermediate AMD to advanced AMD was also assessed in a cross-sectional study evaluating the relationship between each baseline outcome measure and the severity of fundus changes. Sixty participants were recruited of which 47 (20 intervention, 27 control) completed the 12 month follow-up period. No significant difference was found in the change of any parameter between groups apart from the time constant of cone-photoreceptor recovery (cone τ), which was increased to a greater extent in the treated group. An additional 40 participants were recruited to the cross-sectional study (n=100). Measurement of cone τ was identified as the best independent predictor of increased AMD severity based on the AREDS Simplified Severity Scale (Ferris et al., 2005). Although a greater proportion of controls (48%) than mask wearers (38%) showed disease progression over the duration of the trial this difference did not reach statistical significance.