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In the UK, 11,000 new cases of open angle glaucoma (OAG) are diagnosed annually in people aged 40 to 70 years. However, two-thirds of UK OAG cases may remain undiagnosed, highlighting the need for improved detection. UK optometrists generate more than 95% of referrals for suspected glaucoma and ocular hypertension. Case-detection of glaucoma may be improved by using screening tests with better diagnostic accuracy, but standardised protocols for advanced technologies used alone, or in combination, to detect glaucoma are lacking. Chapter 2 reports on two cross-sectional surveys of UK community optometrists, determining the equipment and information technology (IT) used in optometric practice, and exploring the rationale behind the uptake of ophthalmic equipment and IT. UK optometrists are increasingly investing in new ophthalmic equipment and IT, including the latest technology. Longitudinal comparisons with previous surveys revealed an increase in use of Optical coherence tomography (OCT), Goldmann/Perkins tonometry and pachymetry. Variations in responses reflected differences in General Ophthalmic Services provision across the UK and involvement in community enhanced services. There was general agreement that specialised equipment enhances clinical care and permits increased involvement in enhanced services, but initial costs and ongoing maintenance can be a financial burden. Chapter 3 summarises a prospective cross-sectional study investigating the diagnostic accuracy of four advanced technologies for detecting POAG, used alone and in combination, in a representative sample (N=505) of the UK primary care population aged ≥60 years, and compared to a reference standard ophthalmic examination. Structural imaging using the iVue SD-OCT provided better discrimination between POAG and non-POAG/non-OHT subjects than either visual function test (Frequency Doubling Technology or Moorfields Motion Displacement Threshold). The low specificity of visual function tests precludes their use in isolation, but their use together with objective evaluation of optic nerve head structure by SD-OCT should improve case-detection of glaucoma. Chapter 4 describes a case-control study (N=78) evaluating the diagnostic effectiveness of two slit-lamp based techniques (van Herick and Smith’s) and imaging-based systems (Pentacam and Visante OCT) when compared to the reference standard gonioscopic observation, to screen for individuals at-risk of angle closure glaucoma (ACG). Overall, the van Herick test and Visante OCT, used either alone or in combination, showed best discrimination between narrow and open angles. Recording of either the temporal or nasal van Herick grade would be sufficient for case-finding in at-risk individuals. Chapter 5 summarises preceding chapters and details recommendations for future research.

Macular pigment (MP) at the centre of the retina is thought to serve a protective function shielding the photoreceptors from damaging effects of blue light. The amount of MP and its spatial density distribution across the macula i.e. its spatial profile varies among individuals. Lower levels of MP and certain MP spatial profile phenotypes are believed to be associated with increased risk of age-related macular degeneration (AMD). There is suggestion that MP spatial profiles differ between ethnicities, with non-exponential profiles occurring more frequently in non-whites. This may explain some of the ethnic variations seen in AMD prevalence. However, previous investigations have used several methodologies to measure MP. In addition, inconsistent MP spatial profile definitions have been used; thus comparing data between studies is difficult. Nevertheless, it has been hypothesised that variations in MP spatial distribution could be due to differences in foveal architecture, in particular at the foveal centre where MP levels peak. A study was designed to investigate the effect of ethnicity on MP spatial density distribution and its relation to foveal architecture. The influence of known risk factors for AMD was also considered. Young (18 to 39 years), healthy volunteers of white (n = 76), South Asian (n = 80) and black (n = 70) ethnic origin were recruited to take part. MP measurements were obtained using a method based on heterochromatic flicker photometry (HFP) and foveal morphology measurements were taken from optical coherence tomography (OCT) scans. The coefficients of repeatability of each of these were confirmed in a sub-study. A systematic objective MP spatial profile classification technique was implemented throughout. The feasibility of applying this to MP measurements obtained with different techniques such as HFP and fundus autofluorescence (FAF) was also explored in a sub-study. The results showed that measures of MP optical density (MPOD) over the central retinal area were statistically significantly increased in South Asian and black compared to white subjects, whereby ethnicity explained around 10% of the variation (P < 0.0005). Non-exponential MP spatial profiles (ring-like and central dip respectively) were significantly more prevalent in South Asian and black compared with white subjects (χ2 (4, n = 226) = 13.4, P = 0.009). Integrated MPOD up to 1.8º was significantly increased in ring-like and central dip compared to exponential profiles (P < 0.0005) irrespective of ethnicity. South Asian and black individuals presented thinner central retinas and wider foveas compared to white individuals (P < 0.0005). However, while accounting for these ethnic variations, foveal architecture provided no predictive values for the MP spatial profile phenotype.

Introduction. Glistenings are fluid-filled inclusions in the polymer matrix of an intraocular lens (IOL). Acting as refractile particles they may contribute to a reported high level of forward light scatter. However, several studies have reported that there is no significant correlation with a number of measures of visual function. The purpose of the work reported in this thesis was to test if there was an association between in vitro forward light scatter and grade of glistenings. The in vitro approach allows measurement of forward light scatter without the confounding effects of other structures in the eye and subjective responses. Methods. Intraocular lenses were placed at the centre of rotation of a detector stage. The detector measured the forward scattered light in star space at 37 angles covering ±18 degrees. Measurements were made for each of the test lenses at 3mm, 4mm and 5mm pupil sizes. Forward light scatter was quantified by calculating the straylight (volume under the scatter function) for the large angle domain (> 1 deg.). Images of the intraocular lenses were captured with a digital Nikon FS-2 photo slit-lamp. Having developed a Glistenings Detection Programme (GDP) in collaboration with external computer scientists, images were analysed. Results of glistening detection, which included their number, size, density and distribution, were correlated with in vitro forward light scatter measurements. Results. A statistically significant correlation was found between forward light scatter and the number, size and density of glistenings. Comparing our scatter results with the CIE standards, suggests that only high glistenings severity could have an impact on visual function. In addition, results were inversely proportional to pupil size due to the non-uniform distribution of glistenings. The shape of glistenings was shown to be predominantly ellipsoidal rather than spherical. Size and number of glistenings varies in the hydrophobic acrylic materials. Despite the production of new glistenings-free materials, development of glistenings may still exist with cases of high severity giving straylight parameter values greater than those for a cortical cataract subject. A statistically significant difference in MTF and Resolution limit was found in IOLs, pre and post thermal treatment. Finally, a correlation between IOL dioptric power and severity of glistenings was found. Conclusion. Subjective methods for grading intraocular lens glistenings poorly describe the significance of increased light scattering. Image processing software can provide objective data on glistenings density, size and morphology, factors which are important in light scatter modelling. The impact of glistenings on visual function needs further clinical investigation.

The soft contact lenses of today are made from a variety of hydrogel materials. These materials have different properties in terms of water content, monomers, hardness and other tensile characteristics. It is likely that the frictional properties also vary between materials. It is known that constituents of the tear film interact with contact lens materials to form a biofilm on the lens surface. The hypothesis of this research is that although the frictional properties of lens materials may vary these properties do not affect the comfort and performance of the lenses in vivo. A tribometer is a device to measure the coefficient of friction of materials. There was no commercially available tribometer designed specifically for use with contact lens materials, so one was constructed and validated against standard solid materials. The same equipment was used to determine the friction coefficients of five contemporary soft lens materials under different conditions of lubrication but, unlike other tribometers, this unique design simulated human blinking as far as possible. The experimental friction coefficients varied widely from 0.27 to 5.89 under different conditions of lubrication. The largest variation between materials was seen using the most viscous lubricant. For the in vivo studies the author coordinated the manufacture of 250 contact lenses, which were lathe cut and polished to a standard design, achieving exceptionally tight tolerances, using the same five materials. This rigourous process was carried out to minimise variations in the geometry of each contact lens. Subjects were screened to minimise ocular heterogeneities between subjects. Clinical performance of each lens was assessed using comfort, contrast sensitivity, visual acuity, entoptic phenomena, non-invasive tear break-up time and lens movement on the eye. In a clinical environment none of these parameters showed any associations with the coefficients of friction found in vitro, apart from a moderate correlation (rho = 0.5) between lens movement and the coefficient of friction under borderline friction conditions. In conclusion, the findings of this research support the hypothesis that frictional properties of soft lenses do not affect comfort and performance in vivo.

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the developed world. The prevalence of this disease will continue to increase over the coming decades as the average age of the global population rises. There is consequently an urgent need to develop tests that are sensitive to early visual dysfunction, in order to identify individuals that have a high risk of developing AMD, to identify patients that would benefit from treatment, to assess the outcomes of that treatment and to evaluate emerging treatment strategies. An emerging body of evidence suggests that dark adaptation is a sensitive biomarker for early AMD. Cone dark adaptation is of particular interest to clinicians, as it can identify patients with early AMD in a relatively short recording period. Consequently, this thesis aimed to optimise psychophysical and electrophysiological techniques for the assessment of cone dark adaptation in early AMD, in order to maximise its diagnostic potential. A range of psychophysical methods were shown to be capable of monitoring the rapid changes in threshold that occur during cone dark adaptation. An optimal psychophysical protocol for the assessment of cone dark adaptation in early AMD was developed based on the results of a systematic evaluation of the effect of stimulus parameters and pre-adapting light intensity on the diagnostic potential of cone dark adaptation in early AMD. When compared to the focal cone ERG photostress test, both techniques were shown to be similarly diagnostic for early AMD. In addition, the time constant of cone recovery was shown to be significantly correlated with age, hence the sensitivity and specificity of cone dark adaptation as a biomarker for early macular disease may be further improved by considering these age-related changes. In conclusion, this thesis has confirmed that cone dark adaptation is a sensitive functional biomarker for early AMD. However, as cross-sectional studies are unable to determine the true diagnostic potential of a biomarker, longitudinal investigations are needed to explore the long-term potential of cone dark adaptation and other visual functions as biomarkers for early AMD.

In the modern world hair plays a cultural and aesthetic role. The hair care industry accounts for a large portion of the cosmetic and dermatological industry generating large financial sums in sales, and consequently research and development into hair care products is important for companies seeking to increase their market share and profits. Currently there are very few products which specifically target certain ethnicities as the basis of knowledge underlying what nanoscopic and molecular factors cause the variation seen at the macroscale of human hair is circumscribed. Therefore a need exists within this industry to expand the information available on the origins of macroscopic variation in differential ethnic hair types. The work presented in this thesis is the embodiment of five different studies: a bulk X-ray scattering analysis of single hair fibres, a series of skin-core experiments utilising microfocus X-ray scattering, an attenuated total reflectance Fourier transform infrared spectroscopy study of the cuticle surface and a study of the lipids extracted from different spatial locations within hair fibres. The bulk X-ray scattering analysis on single hair fibres showed that the non-keratinous materials; namely the lipids and the amorphous/disordered material and interfaces present are responsible for the largest source of variation seen inter-ethnically at the nanoscopic and supramolecular levels. The lipids were found to be different amongst hair types with respect to their crystalline spacing, the total intensity and thus volume present and also in the preferential structural orientation of the lipid arrangement. The low angle diffuse scatter which is thought to be related to the keratin associated proteins varied with respect to the extent in q range, the angular behaviour and the behaviour of the diffuse scatter under hydration conditions. The azimuthal spread of the reflection arising from the inter-lateral packing of the keratin intermediate filaments was also found to differ between hair types. The skin-core experiments provide information on the textural variation of the hair fibre across the concentric subsections of hair enabling information to be sought on the structural components of the hair. The work presented shows that there are zonal differences in both the keratinous and non-keratinous structures present across the cross-section of the hair fibres both intra and inter-ethnically. The differences seen are in the size and location of specific hierarchical keratinous assembly structures and also in the ultra -structure of the hair fibre as whole. Attenuated total reflectance Fourier transform infrared spectroscopy is a bench top technique that is widely available to investigate the surface structure of materials. The study presented has shown differences related to the keratin conformational structure and the hydrophilic properties of the hair fibres. There are also variations seen in the products of the cysteine containing structures due to weathering which may be due to a difference in the geographical location of the source. Lipids that are present on either the surface of hair fibres or located within the hair fibre account for the largest non-proteinaceous component present in hair. An investigation characterising the lipids preferentially extracted from different spatial locations of the hair fibre has been performed. The work presented has revealed that there is significant variation both intra and inter-ethnically in the total lipid content present, the lipid classes and the fatty acid profiles. The variation in the fatty acid profiles may also possibly be related to the difference in signal seen in the X-ray diffraction study.

Retinal image quality for peripheral as well as central visual field locations has been investigated in humans and an animal model (Columba livia) with wide- angle, panoramic vision because of its laterally oriented eyes. The goal was to determine whether the retinal image is maintained at a higher quality away from the fovea in pigeons as compared to humans. In this thesis, the HSWFS (Hart- mann Shack Wavefront Sensor) has been implemented with the correspondent validation and application for measuring ocular aberrations in the human and avian eye.
Using a modified HSWFS, the refractive error and total amount of ocular aberra- tions were measured for 20 pigeons along the horizontal meridian and for another 8 pigeons in the vertical meridian at three positions along the horizontal meridian. The HOA( High order aberrations) of 10 humans were measured at peripheral locations (±35 ◦) in the upper visual field and along the horizontal meridian. The anaesthetized animal’s head position was controlled by a stereotaxic head holder capable of horizontal and vertical rotation. Measured eccentricities were(±60◦) from the fovea in the horizontal meridian and +35 ◦ and -25 ◦ along each of the three vertical meridians. In pigeons, the LOA (astigmatism) on the horizontal meridian increase slightly from the center towards the far periphery but are relatively constant for ±20◦ around the fovea, whereas defocus remains almost constant. Vertical meridian measurements are consistent with the previously reported myopia in the lower visual field. Compared with measurements in human subjects, the overall values of RMS are much lower in the pigeon at all corresponding eccentricities. Off-axis vision is generally dominated by defocus and astigmatism. In pigeons, however, defocus along the horizontal meridian does not change dramatically whereas, along the vertical meridian, the presence of a lower field myopia is confirmed. Astigmatism of the eye for increasing eccentricity (horizontally and vertically) is consistently lower then expected theoretically and when compared with humans. This demonstrates that the visual optics of the pigeon are more fully corrected for peripheral vision than in humans.

The thesis evaluated, in three studies, the clinical potential of Critical Flicker Fusion perimetry (CFFP) undertaken using the Octopus 311 perimeter. The influence of the learning effect on the outcome of CFFP was evaluated, in each eye at each of five visits each separated by one week, for 28 normal individuals naïve to perimetry, 10 individuals with ocular hypertension (OHT) and 11 with open angle glaucoma (OAG) all of whom were experienced in Standard Automated perimetry (SAP). An improvement occurred in the height, rather than in the shape, of the visual field and was largest for those with OAG. The normal individuals reached optimum performance at the third visit and those with OHT or with OAG at the fourth or fifth visits. The influence of ocular media opacity was investigated in 22 individuals with age-related cataract who were naïve to both SAP and CFFP. All individuals underwent both CFFP and SAP in each eye at each of four visits each separated by one week. At the third and fourth visit, glare disability (GD) was measured with 100% and 10% contrast EDTRS LogMAR visual acuity charts in the presence, and absence, of three levels of glare using the Brightness Acuity Tester. The visual field for CFF improved in height, only. Little correlation was present between the various measures of GD and the visual field, largely due to the narrow range of cataract severity. The influence of optical defocus for both CFFP and SAP was investigated, in one designated eye at each of two visits, in 16 normal individuals all of whom had taken part in the first study. Sensitivity for SAP declined with increase in defocus whilst that for CFFP increased. The latter was attributed to the influence of the Granit-Harper Law arising from the increased size of the defocused stimulus.

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