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.

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.

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.

Protein deposition at polymer surfaces:the bulk and surface structure-property effects of hydrogels

The primary objective of this research has been to investigate the interfacial phenomenon of protein adsorption in relation to the bulk and surface structure-property effect s of hydrogel polymers. In order to achieve this it was first necessary to characterise the bulk and surface properties of the hydrogels, with regard to the structural chemistry of their component monomers. The bulk properties of the hydrogels were established using equilibrium water content measurements, together with water-binding studies by differential scanning calorimetry (D.S.C.). Hamilton and captive air bubble-contact angle techniques were employed to characterise the hydrogel-water interface and from which by a mathematical derivation, the interfacial free energy (ðsw) and the surface free energy components (ð psv, ðdsv, ðsv) were obtained. From the adsorption studies using the radio labelled iodinated (125I) proteins of human serum albumin (H.S.A.) and human fibrinogen (H.Fb.), it was Found that multi-layered adsorption was occurring and that the rate and type of this adsorption was dependent on the physico-chemical behaviour of the adsorbing protein (and its bulk concentration in solution), together with the surface energetics of the adsorbent polymer. A potential method for the invitro evaluation of a material's 'biocompatibility' was also investigated, based on an empirically observed relationship between the adsorption of albumin and fibrinogen and the 'biocompatibility' of polymeric materials. Furthermore, some consideration was also given to the biocompatibility problem of proteinaceous deposit formation on hydrophilic soft' contact lenses and in addition a number of potential continual wear contact lens formulations now undergoing clinical trials,were characterised by the above techniques.

A study of the effects of orally administered female hormones on the volume and composition of lacrimal fluid related to the toleration of corneal contact lenses

This study was designed to evaluate the effects of certain orally active contraceptive steroids on the eye, related to the tolerance of a corneal contact lens. An oestrogen, ethinyloestradiol BP. 0.05 mg, a progestogen, norethisterone acetate BP. 2.50 mg and a control tablet (vitamin C, 50 mg) were utilised. The effect of these preparations on corneal curvature, lacrimal fluid volume and protein composition and directly on corneal lens tolerance was monitored in a group of 23 volunteer patients. The progestogen was found to produce a significant (P≥ 0.05) decrease in tear volume as measured by a 3 minute Schirmer test. A smaller volume reduction was observed with ethinyloestradiol. A normal cornea appears unaffected, within the measurement limits available, by the use of either hormone. However, in the presence of a corneal lens, oestrogen was found to induce substantial corneal steepening, indicative of tissue oedema, during the initial 2-3 weeks of medication. Progestogen occasionally produced a similar effect, which could recur with either hormone shortly after the end of the treatment period. A new method of acrylamide gel electrophoresis was developed for examination of the protein concentration and composition of lacrimal fluid. This allowed much greater resolution of microquantities of unconcentrated fluid than anything previously reported. Quantitation by densitometry has permitted the recording of medication and lens-induced changes in the protein pattern. Tear albumin has been shown to differ from serum albumin and to consist of up to 3 subfractions, 7 further protein fractions may also be resolved. The concentration and probable origin of these proteins have been established and the overall effects of hormone administration described. Individual idiosyncratic responses are also discussed. The study has established tbenature of some effects of contraceptive steroids on the anterior eye, and the probable reasons for resultant corneal lens intolerance.

Visual performance of the human eye with soft hydrophilic contact lenses

The recording of visual acuity using the Snellen letter chart is only a limited measure of the visual performance of an eye wearing a refractive aid. Qualitative in addition to quantitative information is required to establish such a parameter: spatial, temporal and photometric aspects must all be incorporated into the test procedure. The literature relating to the correction of ametropia by refractive aids was reviewed. Selected aspects of a comparison between the correction provided by spectacles and contact lenses were considered. Special attention was directed to soft hydrophilic contact lenses. Despite technological advances which have produced physiologically acceptable soft lenses, there still remain associated with this recent form of refractive aid unpredictable visual factors. Several techniques for vision assessment were described, and previous studies of visual performance were discussed. To facilitate the investigation of visual performance in a clinical environment, a new semi-automated system was described: this utilized the presentation of broken ring test stimuli on a television screen. The research project comprised two stages. Initial work was concerned with the validation of the television system, including the optimization of its several operational variables. The second phase involved the utilization of the system in an investigation of visual performance aspects of the first month of regular daily soft contact lens wear by experimentally-naive subjects. On the basis of the results of this work an ‘homoeostatic’ model has been proposed to represent the strategy which an observer adopts in order to optimize his visual performance with soft contact lenses.

Rotational and centration stability of an aspheric intraocular lens with a simulated toric design

Purpose: To assess the stability of the Akreos AO intraocular lens (IOL) platform with a simulated toric design using objective image analysis. Setting: Six hospital eye clinics across Europe. Methods: After implantation in 1 eye of patients, IOLs with orientation marks were imaged at 1 to 2 days, 7 to 14 days, 30 to 60 days, and 120 to 180 days. The axis of rotation and IOL centration were objectively assessed using validated image analysis. Results: The study enrolled 107 patients with a mean age of 69.9 years ± 7.7 (SD). The image quality was sufficient for IOL rotation analysis in 91% of eyes. The mean rotation between the first day postoperatively and 120 to 180 days was 1.93 ± 2.33 degrees, with 96% of IOLs rotating fewer than 5 degrees and 99% rotating fewer than 10 degrees. There was no significant rotation between visits and no clear bias in the direction of rotation. In 71% of eyes, the dilation and image quality was sufficient for image analysis of centration. The mean change in centration between 1 day and 120 to 180 days was 0.21 ± 0.11 mm, with all IOLs decentering less than 0.5 mm. There was no significant decentration between visits and no clear bias in the direction of the decentration. Conclusion: Objective analysis of digital retroillumination images taken at different postoperative periods shows the aspheric IOL platform was stable in the eye and is therefore suitable for the application of a toric surface to correct corneal astigmatism.

May the contact lens force be with you

FULL TEXT: Like many people one of my favourite pastimes over the holiday season is to watch the great movies that are offered on the television channels and new releases in the movie theatres or catching up on those DVDs that you have been wanting to watch all year. Recently we had the new ‘Star Wars’ movie, ‘The Force Awakens’, which is reckoned to become the highest grossing movie of all time, and the latest offering from James Bond, ‘Spectre’ (which included, for the car aficionados amongst you, the gorgeous new Aston Martin DB10). It is always amusing to see how vision correction or eye injury is dealt with by movie makers. Spy movies and science fiction movies have a freehand to design aliens with multiples eyes on stalks or retina scanning door locks or goggles that can see through walls. Eye surgery is usually shown in some kind of day case simplified laser treatment that gives instant results, apart from the great scene in the original ‘Terminator’ movie where Arnold Schwarzenegger's android character encounters an injury to one eye and then proceeds to remove the humanoid covering to this mechanical eye over a bathroom sink. I suppose it is much more difficult to try and include contact lenses in such movies. Although you may recall the film ‘Charlie's Angels’, which did have a scene where one of the Angels wore a contact lens that had a retinal image imprinted on it so she could by-pass a retinal scan door lock and an Eddy Murphy spy movie ‘I-Spy’, where he wore contact lenses that had electronic gadgetry that allowed whatever he was looking at to be beamed back to someone else, a kind of remote video camera device. Maybe we aren’t quite there in terms of devices available but these things are probably not the behest of science fiction anymore as the technology does exist to put these things together. The technology to incorporate electronics into contact lenses is being developed and I am sure we will be reporting on it in the near future. In the meantime we can continue to enjoy the unrealistic scenes of eye swapping as in the film ‘Minority Report’ (with Tom Cruise). Much more closely to home, than in a galaxy far far away, in this issue you can find articles on topics much nearer to the closer future. More and more optometrists in the UK are becoming registered for therapeutic work as independent prescribers and the number is likely to rise in the near future. These practitioners will be interested in the review paper by Michael Doughty, who is a member of the CLAE editorial panel (soon to be renamed the Jedi Council!), on prescribing drugs as part of the management of chronic meibomian gland dysfunction. Contact lenses play an active role in myopia control and orthokeratology has been used not only to help provide refractive correction but also in the retardation of myopia. In this issue there are three articles related to this topic. Firstly, an excellent paper looking at the link between higher spherical equivalent refractive errors and the association with slower axial elongation. Secondly, a paper that discusses the effectiveness and safety of overnight orthokeratology with high-permeability lens material. Finally, a paper that looks at the stabilisation of early adult-onset myopia. Whilst we are always eager for new and exciting developments in contact lenses and related instrumentation in this issue of CLAE there is a demonstration of a novel and practical use of a smartphone to assisted anterior segment imaging and suggestions of this may be used in telemedicine. It is not hard to imagine someone taking an image remotely and transmitting that back to a central diagnostic centre with the relevant expertise housed in one place where the information can be interpreted and instruction given back to the remote site. Back to ‘Star Wars’ and you will recall in the film ‘The Phantom Menace’ when Qui-Gon Jinn first meets Anakin Skywalker on Tatooine he takes a sample of his blood and sends a scan of it back to Obi-Wan Kenobi to send for analysis and they find that the boy has the highest midichlorian count ever seen. On behalf of the CLAE Editorial board (or Jedi Council) and the BCLA Council (the Senate of the Republic) we wish for you a great 2016 and ‘may the contact lens force be with you’. Or let me put that another way ‘the CLAE Editorial Board and BCLA Council, on behalf of, a great 2016, we wish for you!’

New strategy to overcome the intrinsic difficulty of phospholipids solubilisation and delivery to the eye

Purpose: Lipids play a vital role at interfaces such as the tear film in the protection of the anterior eye. Their role is to act as lubricants and reduce surface and interfacial tension. Although there is a lack of appropriate methods to solubilize and dilute phospholipids to the tear film. Here, we report that styrene-maleic acid copolymers (PSMA), can form polymer–lipid complexes in the form of monodisperse nanometric particles, which can easily solubilise these phospholipid molecules by avoiding for example, the use of any kind of surfactant. Method: The interactions of PSMA with phospholipids have been studied by its adsorption from aqueous solutions into monolayers of dimyristoyl-phosphorylcholine (DMPC). The Langmuir trough (LT) technique is used to study this pH-dependant complex formation. The formed nanoparticles have been also analysed by 31P NMR, particle size distribution by light scattering (DLS) and morphology by electron microscopy (SEM). Results: The LT has been found to be a useful technique for in vitro simulation of in vivo lipid layer behaviour: The limiting surface pressure of unstable tear films ranges between 20 and 30 mN/m. More stable tear films show an increase in surface pressure, within the range of 35–45 mN/m. The DMPC monolayers have a limiting surface pressure of 38 mN/m (water), and 45 mN/m (pH 4 buffer), and the PSMA-DMPC complexes formed at pH 4 have a value of 42 mN/m, which resembles that of the stable tear film. The average particle size distribution is 53 ± 10 nm with a low polydispersity index (PDI) of 0.24 ± 0.03. Conclusions: New biocompatible and cheap lipid solubilising agents such as PSMA can be used for the study of the tear film composition and properties. These polymer–lipid complexes in the form of nanoparticles can be used to solubilise and release in a controlled way other hydrophobic molecules such as some drugs or proteins.

Visual outcomes and subjective experience after bilateral implantation of a new diffractive trifocal intraocular lens

Purpose - To assess clinical outcomes and subjective experience after bilateral implantation of a diffractive trifocal intraocular lens (IOL). Setting - Midland Eye Institute, Solihull, United Kingdom. Design - Cohort study. Methods - Patients had bilateral implantation of Finevision trifocal IOLs. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and manifest refraction were measured 2 months postoperatively. Defocus curves were assessed under photopic and mesopic conditions over a range of +1.50 to -4.00 diopters (D) in 0.50 D steps. Contrast sensitivity function was assessed under photopic conditions. Halometry was used to measure the angular size of monocular and binocular photopic scotomas arising from a glare source. Patient satisfaction with uncorrected near vision was assessed using the Near Activity Visual Questionnaire (NAVQ). Results - The mean monocular CDVA was 0.08 logMAR ± 0.08 (SD) and the mean binocular CDVA, 0.06 ± 0.08 logMAR. Defocus curve testing showed an extended range of clear vision from +1.00 to -2.50 D defocus, with a significant difference in acuity between photopic conditions and mesopic conditions at -1.50 D defocus only. Photopic contrast sensitivity was significantly better binocularly than monocularly at all spatial frequencies. Halometry showed a glare scotoma of a mean size similar to that in previous studies of multifocal and accommodating IOLs; there were no subjective complaints of dysphotopsia. The mean NAVQ Rasch score for satisfaction with near vision was 15.9 ± 10.7 logits. Conclusions - The trifocal IOL implanted binocularly produced good distance visual acuity and near and intermediate visual function. Patients were very satisfied with their uncorrected near vision.

Cataract, macular characteristics and assessing lens opacities

Age-related macular degeneration and cataract are very common causes of visual impairment in the elderly. Macular pigment optical density is known to be a factor affecting the risk of developing age-related macular degeneration but its behaviour due to light exposure to the retina and the effect of macular physiology on this measurement are not fully understood. Cataract is difficult to grade in a way which reflects accurately the visual status of the patient. A new technology, optical coherence tomography, which allows a cross sectional slice of the crystalline lens to be imaged has the potential to be able to provide objective measurements of cataract which could be used for grading purposes. This thesis set out to investigate the effect of cataract removal on macular pigment optical density, the relationship between macular pigment optical density and macular thickness and the relationship between cortical cataract density as measured by optical coherence tomography and other measures of cataract severity. These investigations found: 1) Macular pigment optical density in a pseudophakic eye is reduced when compared to a fellow eye with age related cataract, probably due to differences in light exposure between the eyes. 2) Lower macular pigment optical density is correlated with thinning of the entire macular area, but not with thinning of the fovea or central macula. 3) Central macular thickness decreases with age. 4) Spectral domain optical coherence tomography can be used to successfully acquire images of the anterior lens cortex which relate well to slit lamp lens sections. 5) Grading of cortical cataract with spectral domain optical coherence tomography instruments using a wavelength of 840nm is not well correlated with other established metrics of cataract severity and is therefore not useful as presented as a grading method for this type of cataract.

A decade of silicone hydrogel development:surface properties, mechanical properties, and ocular compatibility

Since the initial launch of silicone hydrogel lenses, there has been a considerable broadening in the range of available commercial material properties. The very mobile silicon–oxygen bonds convey distinctive surface and mechanical properties on silicone hydrogels, in which advantages of enhanced oxygen permeability, reduced protein deposition, and modest frictional interaction are balanced by increased lipid and elastic response. There are now some 15 silicone hydrogel material variants available to practitioners; arguably, the changes that have taken place have been strongly influenced by feedback based on clinical experience. Water content is one of the most influential properties, and the decade has seen a progressive rise from lotrafilcon-A (24%) to efrofilcon-A (74%). Moduli have decreased over the same period from 1.4 to 0.3 MPa, but not solely as a result of changes in water content. Surface properties do not correlate directly with water content, and ingenious approaches have been used to achieve desirable improvements (e.g., greater lubricity and lower contact angle hysteresis). This is demonstrated by comparing the hysteresis value of the earliest (lotrafilcon-A, >40°) and most recent (delefilcon-A, <10°) coated silicone hydrogels. Although wettability is important, it is not of itself a good predictor of ocular response because this involves a much wider range of physicochemical and biochemical factors. The interference of the lens with ocular dynamics is complex leading separately to tissue–material interactions involving anterior and posterior lens surfaces. The biochemical consequences of these interactions may hold the key to a greater understanding of ocular incompatibility and end of day discomfort.

Consensus on recording of gas permeable contact lens fit

Purpose: To develop a new schematic scheme for efficiently recording the key parameters of gas permeable contact lens (GP) fits based on current consensus. Methods: Over 100 established GP fitters and educators met to discuss the parameters proposed in educational material for evaluating GP fit and concluded on the key parameters that should be recorded. The accuracy and variability of evaluating the fluorescein pattern of GP fit was determined by having 35 experienced contact lens practitioners from across the world, grading 5 images of a range of fits and the topographer simulation of the same fits, in random, order using the proposed scheme. The accuracy of the grading was compared to objective image analysis of the fluorescein intensity of the same images. Results: The key information to record to adequately describe the fit of an GP was agreed as: the manufacturer, brand and lens parameters; settling time; comfort on a 5 point scale; centration; movement on blink on a ±2 scale; and the Primary Fluorescein Pattern in the central, mid-peripheral and edge regions of the lens averaged along the horizontal and vertical lens axes, on a ±2 scale. On average 50-60% of practitioners selected the median grade when subjectively rating fluorescein intensity and this was correlated to objective quantification (r= 0.602, p< 0.001). Objective grading suggesting horizontal median fluorescein intensity was generally symmetrical, as was the vertical meridian, but this was not the case for subjective grading. Simulated fluorescein patterns were subjectively and objectively graded as being less intense than real photographs (p< 0.01). Conclusion: GP fit recording can be standardised and simplified to enhance GP practice. © 2013 British Contact Lens Association.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects

Purpose: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Methods: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60. min. The aberration data were analyzed over a 5. mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Results: Hypromellose drops caused an increase in total higher order aberrations (p= <0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p= <0.01, dry eyes p= 0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60. min. Differences in comfort levels failed to reach statistical significance. Conclusion: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. © 2013 British Contact Lens Association.