IN VIVO analysis of ocular morphological changes during phakic accommodation

The principal theme of this thesis is the in vivo examination of ocular morphological changes during phakic accommodation, with particular attention paid to the ciliary muscle and crystalline lens. The investigations detailed involved the application of high-resolution imaging techniques to facilitate the acquisition of new data to assist in the clarification of aspects of the accommodative system that were poorly understood. A clinical evaluation of the newly available Grand Seiko Auto Ref/ Keratometer WAM-5500 optometer was undertaken to assess its value in the field of accommodation research. The device was found to be accurate and repeatable compared to subjective refraction, and has the added advantage of allowing dynamic data collection at a frequency of around 5 Hz. All of the subsequent investigations applied the WAM-5500 for determination of refractive error and objective accommodative responses. Anterior segment optical coherence tomography (AS-OCT) based studies examined the morphology and contractile response of youthful and ageing ciliary muscle. Nasal versus temporal asymmetry was identified, with the temporal aspect being both thicker and demonstrating a greater contractile response. The ciliary muscle was longer in terms of both its anterior (r = 0.49, P <0.001) and overall length (r = 0.45, P = 0.02) characteristics, in myopes. The myopic ciliary muscle does not appear to be merely stretched during axial elongation, as no significant relationship between thickness and refractive error was identified. The main contractile responses observed were a thickening of the anterior region and a shortening of the muscle, particularly anteriorly. Similar patterns of response were observed in subjects aged up to 70 years, supporting a lensocentric theory of presbyopia development. Following the discovery of nasal/ temporal asymmetry in ciliary muscle morphology and response, an investigation was conducted to explore whether the regional variations in muscle contractility impacted on lens stability during accommodation. A bespoke programme was developed to analyse AS-OCT images and determine whether lens tilt and decentration varied between the relaxed and accommodated states. No significant accommodative difference in these parameters was identified, implying that any changes in lens stability with accommodation are very slight, as a possible consequence of vitreous support. Novel three-dimensional magnetic resonance imaging (MRI) and analysis techniques were used to investigate changes in lens morphology and ocular conformation during accommodation. An accommodative reduction in lens equatorial diameter provides further evidence to support the Helmholtzian mechanism of accommodation, whilst the observed increase in lens volume challenges the widespread assertion that this structure is incompressible due to its high water content. Wholeeye MRI indicated that the volume of the vitreous chamber remains constant during accommodation. No significant changes in ocular conformation were detected using MRI. The investigations detailed provide further insight into the mechanisms of accommodation and presbyopia, and represent a platform for future work in this field

Accurate Estimation of Intraocular Pressure and Corneal Material Behaviour Using a Non-Contact Method

The present study is quantifying the effect of corneal parameters(including corneal geometry and material stiffness) with potential considerable influence on intraocular pressure (IOP) and corneal material estimation using finite element method to develop biomechanically-corrected IOP algorithm and biomechanically estimated material algorithm on the non-contact tonometry to estimate higher accurate IOP (with a reduced effect of CCT and age) compared to device’s IOP measurement and the in-vivo corneal material behaviour (with a reduced effect of IOP). The CorVis-ST (Oculus, Wetzlar, Germany) measures IOP using high-speed Scheimpflug technology, which can record the deformation of the cornea during the air pressure application and use this information to define the relationship between the true IOP and dynamic response parameters obtained from CorVis-ST. Hence, in this study the OCULUS CorVis-ST was used for the development of a precise method for estimation of intraocular pressure and corneal material behaviour. Numerical analysis using the finite element method (FEM) had been adapted to represent the operation of the IOP measurement by using the CorVis-ST. The analysis considered the important biomechanical parameters of the eye including IOP, central corneal thickness (CCT), corneal geometry (central radius of curvature, Rc; and anterior corneal asphericity, P), and corneal material behaviour. The numerical simulation results demonstrated higher association of IOP predictions with the first applanation pressure (AP1) rather than CCT and corneal material stiffness (related to age), and higher association of corneal material properties with the ratio between corneal displacement and AP1. The numerical simulation results for healthy and Keratoconic eyes were used as a base to develop algorithms for estimating the true IOP with a reduced effect of CCT and corneal material stiffness, and corneal material behaviour (stress-strain relationship) with a reduced effect of the true IOP. Biomechanically-corrected IOP (bIOP) algorithms for both healthy and keratoconic eyes were validated in clinical data (including healthy, KC, and refractive surgery data) with the aim of significantly reducing IOP dependence on CCT and corneal biomechanics and in experimental ex-vivo human eye tests to assess the accuracy of the bIOP algorithms. The results of experimental ex-vivo human eye tests showed that bIOP had a higher accuracy than the IOP measurement using the CorVis-ST and exhibited no significant correlation with CCT (p=0.756), whereas CVS-IOP was significantly correlated with CCT (p 0.05), In addition, no significant difference in bIOP was found between pre- and post-operative data (0.1±2.1 mmHg, p=0.80 for LASIK and 0.8±1.8 mm Hg, P=0.273 for SMILE), whereas there were significant decreases after surgeries in GAT-IOP (-3.2±3.4 mmHg and -3.2±2.1 mmHg, respectively; both p 0.05) in the values of IOP between healthy and KC patients, using the bIOP and bIOPkc algorithms, while there was a significant difference with CVS-IOP (p0.05) and IOP (p>0.05) but was significantly correlated with age (p<0.01). The stiffness estimates and their variation with age were also significantly correlated (p<0.01) with stiffness estimates obtained in earlier studies on ex-vivo human tissue [1]. In addition, in KC eyes the β predications remain at approximately 80% of the normal cornea’s level. All developed algorithms for IOP and corneal material behaviour estimation demonstrated great success in significantly on providing close estimates of true IOP and corneal material behaviour and reducing the effect of corneal thickness and material stiffness on IOP measurement and the effect of IOP on the corneal material estimation

Optimisation of perimetric stimuli for mapping changes in spatial summation in glaucoma.

Despite being considered the current reference standard for perimetric testing in glaucoma, standard automated perimetry has several cardinal limitations, including an unacceptably high test-retest variability, which increases with increasing depth of defect, and a limited useable dynamic range, with test-retest variability spanning almost the entire instrument range in advanced glaucomatous damage. Prior studies have shown that spatial summation, the mechanism by which the visual system integrates light energy across the area of a stimulus, differs in disease, with an enlarged Ricco’s area (the limit of complete spatial summation) found in individuals with glaucoma. The aim of this work was to investigate whether a perimetric stimulus designed to exploit these changes in spatial summation would enable a greater signal/noise ratio (SNR) than that of the current standard stimulus, by directly measuring the displacement of the spatial summation function in glaucoma. Three stimulus forms were developed; one varying in area alone, one varying in both area and contrast simultaneously, and one varying in contrast alone, all operating within the local Ricco’s area. These novel stimuli were compared with the standard Goldmann III stimulus, in terms of disease signal, noise, and SNR. The experiments presented in this thesis indicate that a stimulus modulating in area alone may offer greater benefits for measuring glaucomatous changes in spatial summation in a clinical setting, in the form of a greater disease signal, more uniform response variability with depth of defect, and greater SNR, when compared with the standard Goldmann III stimulus. Additionally, there is some indication that this stimulus is more robust to the effects of intraocular straylight than the Goldmann III stimulus, although test-retest variability and robustness to optical defocus are largely similar. As this work represents the early investigations of this stimulus, further work is required to examine its translation into a clinical environment

An Exploration of young children’s engagements in research behaviour

Natural research behaviours may present in children younger than eight years but tend to be overlooked by professional researchers, with the result that young children are rarely recognised as agents in enquiry concerning matters affecting them. This exclusion amounts to social injustice as it underestimates children’s capabilities and denies them particular rights. The thesis proposes that young children engage in research activity congruent with professional adult researchers’ behaviours, as part of their daily lives. Furthermore, the inequity caused by excluding children from recognition as researchers may be addressed if professional researchers were to find ways to recognise and value the children’s contributions as researchers. The empirical study that is the focus for the thesis secured a taxonomy of research behaviours from professional adult researchers which was then applied to naturalistic observations conducted with - and by - children aged 4-8 years in their settings and homes. A ‘jigsaw’ methodology was adopted, featuring constructivist grounded theory and critical ethnography, among other methodologies. Throughout, the project was committed to participatory, emancipatory and inductive principles, though challenges were encountered along the way. Alongside observations, multiple other methods and analysis were employed in the co-construction of data with children and their practitioners in three English early childhood settings and children and their parents in five homes. Professional adult researchers also contributed to primary and meta-data. Results indicated that problem solving, exploring, conceptualising and basing decisions on evidence were regarded by professional researchers as the ‘most important’ research behaviours. Children engaged in these behaviours of their own volition, alongside other research behaviours. Their activities included exploring materials to create novel artefacts in art work, rolling in giant cylinders, cooking and ordering objects systematically. While undertaking these activities, children often revealed higher order cognitive processes such as trial and error elimination, causality, analogy and a posteriori conceptualisation. The study produced a ‘plausible account’ suggesting that children aged 4-8 years do engage in research activity naturalistically as part of their daily lives and that this activity is congruent with professional adult researchers’ behaviours