Biochemical markers and contact lens wear

The project objective was to develop a reliable selection procedure to match contact lens materials with individual wearers by the identification of a biochemical marker for assessment of in-eye performance of contact lenses. There is a need for such a procedure as one of the main reasons for contact lens wearers ceasing wearing contact lenses is poor end of day comfort i.e. the lenses become intolerable to the wearer as the day progresses. The selection of an optimal material for individual wearers has the potential benefit to reduce drop Qut, hence increasing the overall contact lens population, and to improve contact lens comfort for established wearers. Using novel analytical methods and statistical techniques, we were able to investigate the interactions between the composition of the tear film and of the biofilm deposited on the contact lenses and contact lens performance. The investigations were limited to studying the lipid components of the tear film; the lipid layer, which plays a key role in preventing evaporation and stabilising the tear film, has been reported to be significantly thinner and of different mixing characteristics during contact lens wear. Different lipid families were found to influence symptomatology, in vivo tear film structure and stability as well as ocular integrity. Whereas the symptomatology was affected by both the tear film lipid composition and the nature of the lipid deposition, the structure of the tear film and its stability were mainly influenced by the tear film lipid composition. The ocular integrity also appeared to be influenced by the nature of the lipid deposition. Potential markers within the lipid species have been identified and could be applied as follows: When required in order to identify a problematic wearer or to match the contact lens material to the contact lens wearer, tear samples collected by the clinician could be dispatched to an analytical laboratory where lipid analysis could be carried out by HPLC. A colorimetric kit based on the lipid markers could also be developed and used by clinician directly in the practice; such a kit would involve tear sampling and classification according to the colour into "Problem", "Border line" and "Good" contact lens wearers groups. A test kit would also have wider scope for marketing in other areas such as general dry-eye pathology.

The tear film and contact lens wear

Contact lenses have become a popular method of vision correction for millions of people globally. As with all devices designed for use within the body, interactions occur between the implanted material and the surrounding biological fluid. A common complaint of lens wearers is that they often experience symptoms of dry eye whilst wearing lenses. This sensation is often heightened towards the end of the day. Through the course of this study, various analytical techniques have been utilised including one dimensional electrophoresis and Western Blotting to study the protein profiles of tear samples. By studying the tears of non-contact lens wearers, it was possible to analyse what could be considered normal, healthy, individuals. A clinical study was also undertaken which followed a population of individuals from the neophyte stage to one whereby they were accustomed lens wearers. Tears were monitored at regular intervals throughout the course of this study and worn contact lenses were also analysed for proteins that had been deposited both on and within the lens. Contact lenses disrupt the tear film in a physical manner by their very presence. They are also thought to cause the normal protein profile to deviate from what would be considered normal. The tear film deposits proteins and lipids onto and within the lens. The lens may therefore be depriving the tear film of certain necessary components. The ultimate aim of this thesis was to discover how, and to what extent, lenses affected tear proteins and if there were any proteins in the tear fluid that had the potential to be used as biochemical markers. Should this be achievable it may be possible to identify those individuals who were more likely to become intolerant lens wearers. This study followed the changes taking place to the tear film as an effect of wearing contact lenses. Twenty-eight patients wore two different types of silicone hydrogel lenses in both a daily wear and a continuous wear regime. The tear protein profiles of the lens-wearers were compared with a control group of non-lens wearing individuals. The considerable amount of data that was generated enabled the clearly observable changes to the four main tear proteins to be monitored.

Mechanisms of convective drying in thick beds of solids

The literature on heat and mass transfer mechanisms in the convective drying of thick beds of solids has been critically reviewed. Related mathematical models of heat transfer are also considered. Experimental and theoretical studies were made of the temperature distribution within beds, and of drying rates, with various materials undergoing convective drying. The experimental work covered thick beds of hygroscopic and non-hygroscopic materials (glass beads of different diameters, polystyrene pellets, activated alumina and wood powder) at air temperatures of 54°C to 84°C. Tests were carried out in a laboratory drying apparatus comprising a wind tunnel through which the air, of controlled temperature and humidity, was passed over a sample suspended from a balance. Thermocouples were inserted at different depths within the sample bed. The temperature distribution profiles for both hygroscopic and non-hygroscopic beds exhibited a clear difference between the temperatures at the surface and bottom during the constant rate period. An effective method was introduced for predicting the critical moisture content. During the falling rate the profiles showed the existence of a receding evaporation plane; this divided the system into a hotter dry zone in the upper section and a wet zone near the bottom. A graphical procedure was established to predict accurately the position of the receding evaporation front at any time. A new mathematical model, based on the receding evaporation front phenomenon, was proposed to predict temperature distributions throughout a bed during drying. Good agreement was obtained when the model was validated by comparing its predictions with experimental data. The model was also able to predict the duration of each drying stage. In experiments using sample trays of different diameters, the drying rate was found to increase with a decrease in the effective length of the bed surface. During the constant rate period with trays of a small effective length, i.e. less than 0.08 m, an 'inversion' in temperature distribution occurred in the bed; the bottom temperature increased and became greater than that of the surface. Experimental measurements were verified in several ways to ensure this phenomenon was real. Theoretical explanations are given for both the effective length and temperature inversion phenomena.

Development of a non-destructive fluorescence technique for analysis of contact lens deposition levels

The primary objective of this research has been to determine the potential of fluorescence spectroscopy as a method for analysis of surface deposition on contact lenses. In order to achieve this it was first necessary to ascertain whether fluorescence analysis would be able to detect and distinguish between protein and lipid deposited on a lens surface. In conjunction with this it was important to determine the specific excitation wavelengths at which these deposited species were detected with the greatest sensitivity. Experimental observations showed that an excitation wavelength of 360nm would detect lipid deposited on a lens surface, and an excitation wavelength of 280nm would detect and distinguish between protein and lipid deposited on a contact lens. It was also very important to determine whether clean unspoilt lenses showed significant levels of fluorescence themselves. Fluorescence spectra recorded from a variety of unworn contact lenses at excitation wavelengths of 360nm and 280nm indicated that most contact lens materials do not fluoresce themselves to any great extent. Following these initial experiments various clinically and laboratory based studies were performed using fluorescence spectroscopy as a method of analysing contact lens deposition levels. The clinically based studies enabled analysis of contact lenses with known wear backgrounds to be rapidly and individually analysed following discontinuation of wear. Deposition levels in the early stages of lens wear were determined for various lens materials. The effect of surfactant cleaning on deposition levels was also investigated. The laboratory based studies involved comparing some of the in vivo results with those of identical lenses that had been spoilt using an in vitro method. Finally, an examination of lysosyme migration into and out of stored ionic high water contact lenses was made.

Analytical techniques for the study of soft contact lens spoilation

Soft contact lens wear has become a common phenomenon in recent times. The contact lens when placed in the eye rapidly undergoes change. A film of biological material builds up on and in the lens matrix. The long term wear characteristics of the lens ultimately depend on this process. With time distinct structures made up of biological material have been found to build up on the lens. A fuller understanding of this process and how it relates to the lens chemistry could lead to contact lenses that are better tolerated by the eye. The tear film is a complex biological fluid, it is this fluid that bathes the lens during wear. It is reasonable to suppose that it is material derived from this source that accumulates on the lens. To understand this phenomenon it was decided to investigate the make up and conformation of the protein species that are found on and in the lens. As inter individual variations in tear fluid composition have been found it is important to be able to study the proteins on a single lens. Many of the analytical techniques used in bio research are not suitable for this study because of the lack of sensitivity. Work with poly acrylamide electrophoresis showed the possibility of analyzing the proteins extracted from a single lens. The development of a biotin avidin electro-blot and an enzyme linked aniibody electro-blot, lead to the high sensitivity detection and identification of the proteins present. The extraction of proteins from a lens is always incomplete. A method that analyses the proteins in situ would be a great advancement. Fourier transform infra red microscopy was developed to a point where a thin section of a contact lens could yield information about the proteins present and their conformation. The three dimensional structure of the gross macroscopic structures termed white spots was investigated using confocal laser microscopy.

A sensitivity study of the human crystalline lens using finite element analysis

Finite element analysis is a useful tool in understanding how the accommodation system of the eye works. Further to simpler FEA models that have been used hitherto, this paper describes a sensitivity study which aims to understand which parameters of the crystalline lens are key to developing an accurate model of the accommodation system. A number of lens models were created, allowing the mechanical properties, internal structure and outer geometry to be varied. These models were then spun about their axes, and the deformations determined. The results showed the mechanical properties are the critical parameters, with the internal structure secondary. Further research is needed to fully understand how the internal structure and properties interact to affect lens deformation.

Visual comparison of multifocal contact lens to monovision

Purpose. To compare visual function with the Bausch & Lomb PureVision multifocal contact lens to monovision with PureVision single vision contact lenses. Methods. Twenty presbyopic subjects were fitted with either the PureVision multifocal contact lens or monovision with PureVision singlevision lenses. Aftera 1-month trial, the following assessments of visual function were made: (a) distance, intermediate, and near visual acuity (VA); (b) reading ability; (c) distance and near contrast sensitivity function (CSF); (d) near range of clear vision; (e) stereoacuity; and (f) subjective evaluation of near vision ability with a standardized questionnaire. Subjects were then refitted with the alternative correction and the procedure was repeated. All measurements were compared between the two corrections, whereas the ``low addition'' multifocal lens was also compared with the ``high addition'' alternative. Results. Distance and near VA were significantly better with monovision than with the multifocal option (p < 0.05). Intermediate VA (p = 0.13) was similar with both corrections, whereas there was also no significant difference in distance and near CSF (p = 0.29 on both occasions). Reading speeds (p = 0.48) and the critical print size (p = 0.90) were not significantly different between the two contact lens corrections, but stereoacuity (p < 0.01) and the near range of clear vision (p < 0.05) were significantly better with the multifocal option than with monovision. Subjective assessment of near ability was similar for both types of contact lens (p = 0.52). The high addition multifocal lens produced significantly poorer distance and near CSF, near VA, and critical print size compared with the low addition alternative. Conclusions. Monovision performed better than a center-near aspheric simultaneous vision multifocal contact lens of the same material for distance and near VA only. The multifocal option provides better stereoacuity and near range of clear vision, with little differences in CSF, so a better balance of real-world visual function may be achieved due to minimal binocular disruption. (Optom Vis Sci 2009;86:98-105)

Development of an on-demand beam pulsing system for Pixe-analysis of thick targets

This work concerns the developnent of a proton irduced X-ray emission (PIXE) analysis system and a multi-sample scattering chamber facility. The characteristics of the beam pulsing system and its counting rate capabilities were evaluated by observing the ion-induced X-ray emission from pure thick copper targets, with and without beam pulsing operation. The characteristic X-rays were detected with a high resolution Si(Li) detector coupled to a rrulti-channel analyser. The removal of the pile-up continuum by the use of the on-demand beam pulsing is clearly demonstrated in this work. This new on-demand pu1sirg system with its counting rate capability of 25, 18 and 10 kPPS corresponding to 2, 4 am 8 usec main amplifier time constant respectively enables thick targets to be analysed more readily. Reproducibility tests of the on-demard beam pulsing system operation were checked by repeated measurements of the system throughput curves, with and without beam pulsing. The reproducibility of the analysis performed using this system was also checked by repeated measurements of the intensity ratios from a number of standard binary alloys during the experimental work. A computer programme has been developed to evaluate the calculations of the X-ray yields from thick targets bornbarded by protons, taking into account the secondary X-ray yield production due to characteristic X-ray fluorescence from an element energetically higher than the absorption edge energy of the other element present in the target. This effect was studied on metallic binary alloys such as Fe/Ni and Cr/Fe. The quantitative analysis of Fe/Ni and Cr/Fe alloy samples to determine their elemental composition taking into account the enhancement has been demonstrated in this work. Furthermore, the usefulness of the Rutherford backscattering (R.B.S.) technique to obtain the depth profiles of the elements in the upper micron of the sample is discussed.

The sedimentology and diagenesis of the Pendleside limestone group in the Craven Basin of Northern England. Available in 2 volumes.

This thesis describes the stratigraphy, sedimentology and diagenesis of the Pendleside Limestone (Asbian age), a sequence of limestones, shales and dolostones in the Clitheroe area of N. W. England. Field study of 19 measured sections indicates that it was deposited in a rhythmically subsiding basin (Craven Basin) because of movements on the Mid-Craven Fault which was active in Dinantian times. The sequence is up to 190m thick and consists mostly of distal turbidite deposits which have been reworked at horizons when sediment accumulation built up to the wave base. The original depositional fabric and mineralogy of the Pendleside Limestone Group has been extensively modified by diagenetic processes including cementation, authi­genesis, dolomitization and silicification. These processes have been studied using a wide variety of laboratory techniques. The carbonate cements of the PendIeside Limestone consist predominantly of ferroan calcite and non-ferroan calcite with microdolomite incIusions. The former is probably a stable replacement of original-high-magnesian calcite. Cementation was accompanied by the formation of authigenic albite and quartz. Much of the upper part of the Pendleside Limestone has been extensively dolomitized and chertified. Several distinct zones of dolomitization are found which increase in thickness and intensity towards the top of the Pendleside Limestone Group. The dolostone horizons correspond to coarser-grained lithologies deposited during periods of shallow water sedimentation. The composition of the dolomites changes from ferroan dolomite in the lower part of the Group to non-ferroan dolomite in the upper part. The low strontium and sodium content of the dolostones in association with the other evidence suggests that the dolomitization was brought about in an open system by the mixing of marine and fresh water in phreatic lens which were established at periodic intervals. The dolomitization was closely associated with chertification although this was initiated by the dissolution of siliceous spicules which provided the necessary source of silica.

An analysis of progressive addition spectacles lens design by the use of interferometry

Progressive addition spectacle lenses (PALs) have now become the method of choice for many presbyopic individuals to alleviate the visual problems of middle-age. Such lenses are difficult to assess and characterise because of their lack of discrete geographical locators of their key features. A review of the literature (mostly patents) describing the different designs of these lenses indicates the range of approaches to solving the visual problem of presbyopia. However, very little is published about the comparative optical performance of these lenses. A method is described here based on interferometry for the assessment of PALs, with a comparison of measurements made on an automatic focimeter. The relative merits of these techniques are discussed. Although the measurements are comparable, it is considered that the interferometry method is more readily automated, and would be ultimately capable of producing a more rapid result.