Mechanism of action of the tetraflex accommodative intraocular lens

PURPOSE:To investigate the mechanism of action of the Tetraflex (Lenstec Kellen KH-3500) accommodative intraocular lens (IOL). METHODS:Thirteen eyes of eight patients implanted with the Tetraflex accommodating IOL for at least 2 years underwent assessment of their objective amplitude-of-accommodation by autorefraction, anterior chamber depth and pupil size with optical coherence tomography, and IOL flexure with aberrometry, each viewing a target at 0.0 to 4.00 diopters of accommodative demand. RESULTS:Pupil size decreased by 0.62+/-0.41 mm on increasing accommodative demand, but the Tetraflex IOL was relatively fixed in position within the eye. The ocular aberrations of the eye changed with increased accommodative demand, but not in a consistent manner among individuals. Those aberrations that appeared to be most affected were defocus, vertical primary and secondary astigmatism, vertical coma, horizontal and vertical primary and secondary trefoil, and spherical aberration. CONCLUSIONS:Some of the reported near vision benefits of the Tetraflex accommodating IOL appear to be due to changes in the optical aberrations because of the flexure of the IOL on accommodative effort rather than forward movement within the capsular bag.

Ocular biotribology and contact lens lubrication mechanisms

The work described in this thesis is concerned with mechanisms of contact lens lubrication. There are three major driving forces in contact lens design and development; cost, convenience, and comfort. Lubrication, as reflected in the coefficient of friction, is becoming recognised as one of the major factors affecting the comfort of the current generation of contact lenses, which have benefited from several decades of design and production improvements. This work started with the study of the in-eye release of soluble macromolecules from a contact lens matrix. The vehicle for the study was the family of CIBA Vision Focus® DAILIES® daily disposable contact lenses which is based on polyvinyl alcohol (PVA). The effective release of linear soluble PVA from DAILIES on the surface of the lens was shown to be beneficial in terms of patient comfort. There was a need to develop a novel characterisation technique in order to study these effects at surfaces; this led to the study of a novel tribological technique, which allowed the friction coefficients of different types of contact lenses to be measured reproducibly at genuinely low values. The tribometer needed the ability to accommodate the following features: (a) an approximation to eye lid load, (b) both new and ex-vivo lenses, (c) variations in substrate, (d) different ocular lubricants (including tears). The tribometer and measuring technique developed in this way was used to examine the surface friction and lubrication mechanisms of two different types of contact lenses: daily disposables and silicone hydrogels. The results from the tribometer in terms of both mean friction coefficient and the friction profiles obtained allowed various mechanisms used for surface enhancement now seen in the daily disposable contact lens sector to be evaluated. The three major methods used are: release of soluble macromolecules (such as PVA) from the lens matrix, irreversible surface binding of a macromolecule (such as polyvinyl pyrrolidone) by charge transfer and the simple polymer adsorption (e.g. Pluoronic) at the lens surface. The tribological technique was also used to examine the trends in the development of silicone hydrogel contact lenses. The focus of the principles in the design of silicone hydrogels has now shifted from oxygen permeability, to the improvement of surface properties. Presently, tribological studies reflect the most effective in vitro method of surface evaluation in relation to the in-eye comfort.

Dehydration at the lens surface:surface energy and surfactant persistence

Purpose: Most published surface wettability data are based on hydrated materials and are dominated by the air-water interface. Water soluble species with hydrophobic domains (such as surfactants) interact directly with the hydrophobic domains in the lens polymer. Characterisation of relative polar and non-polar fractions of the dehydrated material provides an additional approach to surface analysis. Method: Probe liquids (water and diiodomethane) were used to characterise polar and dispersive components of surface energies of dehydrated lenses using the method of Owens and Wendt. A range of conventional and silicone hydrogel soft lenses was studied. The polar fraction (i.e. polar/total) of surface energy was used as a basis for the study of the structural effects that influence surfactant persistence on the lens surface. Results: When plotted against water content of the hydrated lens, polar fraction of surface energy (PFSE) values of the dehydrated lenses fell into two rectilinear bands. One of these bands covered PFSE values ranging from 0.4 to 0.8 and contained only conventional hydrogels, with two notable additions: the plasma coated silicone hydrogels lotrafilcon A and B. The second band covered PFSE values ranging from 0.04 to 0.28 and contained only silicone hydrogels. Significantly, the silicone hydrogel lenses with lowest PFSE values (p<0.15) are found to be prone to lipid deposition duringwear. Additionally, more hydrophobic surfactants were found to be more persistent on lenses with lower PFSE values. Conclusions: Measurement of polar fraction of surface energy provides an importantmechanistic insight into surface interactions of silicone hydrogels.

Clinical evaluation of the Softec HD aberration-free aspheric intraocular lens

Purpose: To compare distance and near visual performance with a zero-aberration aspheric intraocular lens (IOL) (Softec HD, Lenstec, Inc. FL, USA) with that of an otherwise identical, but spherical IOL (Softec 1). Setting: Department of Ophthalmology, Solihull Hospital, West Midlands, United Kingdom. Methods: This prospective study comprised 37 patients with a Softec 1 spherical IOL implanted in one eye, who underwent phacoemulsification and received the Softec HD aspheric IOL in the fellow eye. One month post-operatively, unaided distance and near vision, residual refraction, best spectacle corrected distance and near visual acuity, reading speed, pseudoaccommodation and photopic contrast sensitivity were recorded. Wavefront analysis enabled comparison of higher order aberrations between the IOLs. Results: Prior to surgery, the Softec 1 and Softec HD eyes were not significantly different. Post-operatively, unaided vision, best spectacle corrected visual acuity and residual refraction were not significantly different between the eyes, nor were there significant differences observed between the measured wavefront aberrations. Once implanted, the range of focus was significantly better in the Softec HD IOL eye than the Softec 1 IOL eye and, although reading speed was equivalent to the Softec 1 eye, the print size at which this could be achieved was significantly smaller. Conclusions: Depth of field was significantly improved with the aspheric IOL compared with the spherical IOL, without any compromise in distance visual performance between the two IOLs.

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.

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.

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)

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.

Ocular biometric correlates of early-and late-onset myopia

Myopia is a refractive condition and develops because either the optical power of the eye is abnormally great or the eye is abnormally long, the optical consequences being that the focal length of the eye is too short for the physical length of the eye. The increase in axial length has been shown to match closely the dioptric error of the eye, in that a lmm increase in axial length usually generates 2 to 3D of myopia. The most common form of myopia is early-onset myopia (EO M) which occurs between 6 to 14 years of age. The second most common form of myopia is late-onset myopia (LOM) which emerges in late teens or early twenties, at a time when the eye should have ceased growing. The prevalence of LOM is increasing and research has indicated a link with excessive and sustained nearwork. The aim of this thesis was to examine the ocular biometric correlates associated with LOM and EOM development and progression. Biometric data was recorded on SO subjects, aged 16 to 26 years. The group was divided into 26 emmetropic subjects and 24 myopic subjects. Keratometry, corneal topography, ultrasonography, lens shape, central and peripheral refractive error, ocular blood flow and assessment of accommodation were measured on three occasions during an ISmonth to 2-year longitudinal study. Retinal contours were derived using a specially derived computer program. The thesis shows that myopia progression is related to an increase in vitreous chamber depth, a finding which supports previous work. The myopes exhibited hyperopic relative peripheral refractive error (PRE) and the emmetropes exhibited myopic relative PRE. Myopes demonstrated a prolate retinal shape and the retina became more prolate with myopia progression. The results show that a longitudinal, rather than equatorial, increase in the posterior segment is the principal structural correlate of myopia. Retinal shape, relative PRE and the ratio of axial length to corneal curvature have been indicated, in this thesis, as predictive factors for myopia onset and development. Data from this thesis demonstrates that myopia progression in the LOM group is the result of an increase in anterior segment power, owing to an increase in lens thickness, in conjunction with posterior segment elongation. Myopia progression in the EOM group is the product of a long posterior segment, which over-compensates for a weak anterior segment power. The weak anterior segment power in the EOM group is related to a combination of crystalline lens thinning and surface flattening. The results presented in this thesis confirm that posterior segment elongation is the main structural correlate in both EOM and LOM progression. The techniques and computer programs employed in the thesis are reproducible and robust providing a valuable framework for further myopia research and assessment of predictive factors.

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.