The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

Objective analysis of toric intraocular lens rotation and centration

PURPOSE: To assess the repeatability of an objective image analysis technique to determine intraocular lens (IOL) rotation and centration. SETTING: Six ophthalmology clinics across Europe. METHODS: One-hundred seven patients implanted with Akreos AO aspheric IOLs with orientation marks were imaged. Image quality was rated by a masked observer. The axis of rotation was determined from a line bisecting the IOL orientation marks. This was normalized for rotation of the eye between visits using the axis bisecting 2 consistent conjunctival vessels or iris features. The center of ovals overlaid to circumscribe the IOL optic edge and the pupil or limbus were compared to determine IOL centration. Intrasession repeatability was assessed in 40 eyes and the variability of repeated analysis examined. RESULTS: Intrasession rotational stability of the IOL was ±0.79 degrees (SD) and centration was ±0.10 mm horizontally and ±0.10 mm vertically. Repeated analysis variability of the same image was ±0.70 degrees for rotation and ±0.20 mm horizontally and ±0.31 mm vertically for centration. Eye rotation (absolute) between visits was 2.23 ± 1.84 degrees (10%>5 degrees rotation) using one set of consistent conjunctival vessels or iris features and 2.03 ± 1.66 degrees (7%>5 degrees rotation) using the average of 2 sets (P =.13). Poorer image quality resulted in larger apparent absolute IOL rotation (r =-0.45,P<.001). CONCLUSIONS: Objective analysis of digital retroillumination images allows sensitive assessment of IOL rotation and centration stability. Eye rotation between images can lead to significant errors if not taken into account. Image quality is important to analysis accuracy.

Development of a near activity visual questionnaire to assess accommodating intraocular lenses

Purpose: To develop a questionnaire that subjectively assesses near visual function in patients with 'accommodating' intraocular lenses (IOLs). Methods: A literature search of existing vision-related quality-of-life instruments identified all questions relating to near visual tasks. Questions were combined if repeated in multiple instruments. Further relevant questions were added and item interpretation confirmed through multidisciplinary consultation and focus groups. A preliminary 19-item questionnaire was presented to 22 subjects at their 4-week visit post first eye phacoemulsification with 'accommodative' IOL implantation, and again 6 and 12 weeks post-operatively. Rasch Analysis, Frequency of Endorsement, and tests of normality (skew and kurtosis) were used to reduce the instrument. Cronbach's alpha and test-retest reliability (intraclass correlation coefficient, ICC) were determined for the final questionnaire. Construct validity was obtained by Pearson's product moment correlation (PPMC) of questionnaire scores to reading acuity (RA) and to Critical Print Size (CPS) reading speed. Criterion validity was obtained by receiver operating characteristic (ROC) curve analysis and dimensionality of the questionnaire was assessed by factor analysis. Results: Rasch Analysis eliminated nine items due to poor fit statistics. The final items have good separation (2.55), internal consistency (Cronbach's α = 0.97) and test-retest reliability (ICC = 0.66). PPMC of questionnaire scores with RA was 0.33, and with CPS reading speed was 0.08. Area under the ROC curve was 0.88 and Factor Analysis revealed one principal factor. Conclusion: The pilot data indicates the questionnaire to be internally consistent, reliable and a valid instrument that could be useful for assessing near visual function in patients with 'accommodating' IOLS. The questionnaire will now be expanded to include other types of presbyopic correction. © 2007 British Contact Lens Association.

Influence of accommodation and refractive status on the peripheral refractive profile

AIM: The aim of the study was to determine, objectively and non-invasively, whether changes in accommodative demand modify differentially the peripheral refraction in emmetropic and myopic human eyes. METHODS: Forty subjects (19 male, 21 female) aged 20-30 years (mean 22.7 (SD 2.8) years), 21 emmetropes (mean spherical equivalent refractive error (MSE) -0.13 (SD 0.29) D) and 19 myopes (MSE -2.95 (SD 1.76) D) participated in the study. Ametropia was corrected with soft contact lenses (etafilcon A, 58% water content). Subjects viewed monocularly a stationary, high contrast (85%) Maltese cross at 0.0, 1.0, 2.0 and 3.0 D of accommodative demand and at 0, 10, 20 and 30 degrees field angle (nasal and temporal) through a +3.0 D Badal optical system. Static recordings of the accommodation response were obtained for each accommodative level, at each field angle, with an objective, open-view, infrared optometer. RESULTS: Peripheral mean spherical equivalent (M) data showed that the emmetropic cohort exhibited relative myopic shifts into the periphery, while the myopic group showed hypermetropic shifts. Increasing accommodative demand did not alter the peripheral refractive profile in either the temporal (p = 0.25) or nasal (p = 0.07) periphery with no differential accommodative effect between refractive groups in either the temporal (p = 0.77) or nasal (p = 0.73) field. Significant shifts in the J(0) astigmatic component were seen in the temporal (p<0.0005) and nasal (p<0.0005) fields with increasing eccentricity. Interaction effects between eccentricity and accommodative demand illustrated that increasing accommodative demand significantly altered the peripheral refractive profile in the temporal J(0) astigmatic component (p<0.0005). The nasal periphery, however, failed to show such an effect (p = 0.65). CONCLUSIONS: Alterations in peripheral refraction augmented by changes in ocular accommodation are relatively unaffected by refractive error for young, healthy human eyes.

Development of a prescribing indicator for objective quantification of antibiotic usage in secondary care

Objectives: To compare the recognized defined daily dose per 100 bed-days (DDD/100 bed-days) measure with the defined daily dose per finished consultant episode (DDD/FCE) in a group of hospitals with a variety of medicines management strategies. To compare antibiotic usage using the above indicators in hospitals with and without electronic prescribing systems. Methods: Twelve hospitals were used in the study. Nine hospitals were selected and split into three cohorts (three high-scoring, three medium-scoring and three low-scoring) by their 2001 medicines management self-assessment scores (MMAS). An additional cohort of three electronic prescribing hospitals was included for comparison. MMAS were compared to antibiotic management scores (AMS) developed from a questionnaire relating specifically to control of antibiotics. FCEs and occupied bed-days were obtained from published statistics and statistical analyses of the DDD/100 bed-days and DDD/FCE were carried out using SPSS. Results: The DDD/100 bed-days varied from 81.33 to 189.37 whilst the DDD/FCE varied from 2.88 to 7.43. The two indicators showed a high degree of correlation with r = 0.74. MMAS were from 9 to 22 (possible range 0-23) and the AMS from 2 to 13 (possible range 0-22). The two scores showed a high degree of correlation with r = 0.74. No correlation was established between either indicator and either score. Conclusions: The WHO indicator for medicines utilization, DDD/100 bed-days, exhibited the same level of conformity as that exhibited from the use of the DDD/FCE indicating that the DDD/FCE is a useful additional indicator for identifying hospitals which require further study. The MMAS can be assumed to be an accurate guide to antibiotic medicines management controls. No relationship has been found between a high degree of medicines management control and the quantity of antibiotic prescribed. © The British Society for Antimicrobial Chemotherapy; 2004 all rights reserved.

An evaluation of quinolone prescribing in a group of acute hospitals:Development of an objective measure of usage

Objectives: To develop an objective measure to enable hospital Trusts to compare their use of antibiotics. Design: Self-completion, postal questionnaire with telephone follow up. Sample: 4 hospital trusts in the English Midlands. Results: The survey showed that it was possible to collect data concerning the number of Defined Daily Doses (DDD's) of quinolone antibiotic dispensed per Finished Consultant Episode (FCE) in each Trust.. In the 4 trusts studied the mean DDD/FCE was 0.197 (range 0.117 to 0.258). This indicates that based on a typical course length of 5 days, 3.9% of patient episodes resulted in the prescription of a quinolone antibiotic. Antibiotic prescribing control measures in each Trust were found to be comparable. Conclusion: The measure will enable Trusts to objectively compare their usage of quinolone antibiotics and use this information to carry out clinical audit should differences be recorded. This is likely to be applicable to other groups of antibiotics.

Intraocular lenses in the 21st century

Editorial

Cellular interaction with novel biomaterials

The objective of this thesis is to report the behaviour of mammalian cells with biocompatible synthetic polymers with potential for applications to the human body. Composite hydrogel materials were tested as possible keratoprosthetic devices. It was found that surface topography is an important consideration, pores, channels and fibres exposed on the surface of the hydrogels tested can have significant effects on the extent of cell adheson and proliferation. It is recommended that the core component is fabricated out of one of the following to provide a non cell adhesive base; A8, A11, A13, A22, A23. The haptic periphery fabricated out of one of the following would provide a cell adhesive composite; A16, A30, A33, A37, A38, A42, A43, A44. The presence of vitronectin in the ocular tissue appears to lead to higher cell adhesion to the posterior surface of a contact lens when compared to the anterior surface. Group IV contact lenses adhere more cells than Group II contact lenses - this may indicate that more protein (including vitronectin) is able to adhere to the contact lens due to the Group IV contact lenses high water content and ionic hydrogel matrix. Artificial lung surfactant analogues were found to be non cytotoxic but also decreased cell proliferation when tested at higher concentrations. Poly(lysine ethyl ester adipamide) [PLETESA] had the most favourable response on cell proliferation and commercial styrene/maleic anhydride (pMA/STY sp2) the most pronounced inhibitory response. The mode of action that decreases cell proliferation appears to be through membrane destabilization. Tissue culture well plates coated with PLETESA allowed cells to adhere in a concentration dependent manner, multilaminar liposomes possibly of PLETESA were observed in solution in PLETESA coated wells. Polyhydroxybutryate (PHB) and polyhydroxyvalerate (PHV) blends that contained hydroxyapatite were found to be the most cell adhesive material of those materials tested. The blends that were most susceptible to degradation adhered the most cells in initial stages of degradation. The initial slight increase in cell adhesion may be due to the increased rugosity of the material. As the degradation continued the number of cells adhering to the samples decreased, this may indicate that the polarity was inhibitory to cell adhesion during the later stages of degradation.

A novel plasma etching and emission monitoring system (PEEMS) to assess protein and lipid spoilation for hydrogel contact lenses

The work presents a new method that combines plasma etching with extrinsic techniques to simultaneously measure matrix and surface protein and lipid deposits. The acronym for this technique is PEEMS - Plasma Etching and Emission Monitoring System. Previous work has identified the presence of proteinaceous and lipoidal deposition on the surface of contact lenses and highlighted the probability that penetration of these spoilants will occur. This technique developed here allows unambiguous identification of the depth of penetration of spoilants to be made for various material types. It is for this reason that the technique has been employed in this thesis. The technique is applied as a 'molecular' scalpel, removing known amounts of material from the target. In this case from both the anterior .and posterior surfaces of a 'soft' contact lens. The residual material is then characterised by other analytical techniques such as UV/visible .and fluorescence spectroscopy. Several studies have be.en carried out for both in vivo and in vitro spoilt materials. The analysis and identification of absorbed protein and lipid of the substrate revealed the importance of many factors in the absorption and adsorption process. The effect of the material structure, protein nature (in terms of size, shape and charge) and environment conditions were examined in order to determine the relative uptake of tear proteins. The studies were extended to real cases in order to study the. patient dependent factors and lipoidal penetration.

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.

Ocular compatibility of hydrogel contact lenses:deposition and clinical performance

Currently over 50 million people worldwide wear contact lenses, of which over 75% wear hydrogel lenses. Significant deposition occurs in approximately 80% of hydrogel lenses and many contact lens wearers cease wearing lenses due to problems associated with deposition. The contact lens field is not alone in encountering complications associated with interactions between the body and artificial devices. The widespread use of man-made materials to replace structures in the body has emphasised the importance of studies that examine the interactions between implantation materials and body tissues.This project used carefully controlled, randomized clinical studies to study the interactive effects of contact lens materials, care systems, replacement periods and patient differences. Of principal interest was the influence of these factors on material deposition and their subsequent impact on subjective performance. A range of novel and established analytical techniques were used to examine hydrogel lenses following carefully controlled clinical studies in which clinical performance was meticulously monitored. These studies established the inter-relationship between clinical performance and deposition to be evaluated. This project showed that significant differences exist between individuals in their ability to deposit hydrogel lenses, with approximately 20% of subjects displaying significant deposition irrespective of the lens material. Additionally, materials traditionally categorised together show markedly different spoilation characteristics, which are wholly attributable to their detailed chemical structure. For the first time the in vivo deposition kinetics of both protein and lipid in charged and uncharged polymers was demonstrated. In addition the importance of care systems in the deposition process was shown, clearly demonstrating the significance of the quality rather than the quantity of deposition in influencing subjective performance.

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.

Tear protein interaction with hydrogel contact lenses

The design and synthesis of biomaterials covers a growing number of biomedical applications. The use of biomaterials in biological environment is associated with a number of problems, the most important of which is biocompatabUity. If the implanted biomaterial is not compatible with the environment, it will be rejected by the biological site. This may be manifested in many ways depending on the environment in which it is used. Adsorption of proteins takes place almost instantaneously when a biomaterial comes into contact with most biological fluids. The eye is a unique body site for the study of protein interactions with biomaterials, because of its ease of access and deceptive complexity of the tears. The use of contact lenses for either vision correction and cosmetic reasons or as a route for the controlled drug delivery, has significantly increased in recent years. It is relatively easy to introduce a contact lens Into the tear fluid and remove after a few minutes without surgery or trauma to the patient. A range of analytical techniques were used and developed to measure the proteins absorbed to some existing commercial contact lens materials and also to novel hydrogels synthesised within the research group. Analysis of the identity and quantity of proteins absorbed to biomaterials revealed the importance of many factors on the absorption process. The effect of biomaterial structure, protein nature in terms of size. shape and charge and pH of the environment on the absorption process were examined in order to determine the relative up-take of tear proteins. This study showed that both lysozyme and lactoferrin penetrate the lens matrix of ionic materials. Measurement of the mobility and activity of the protein deposited into the surface and within the matrix of ionic lens materials demonstrated that the mobility is pH dependent and, within the experimental errors, the biological activity of lysozyme remained unchanged after adsorption and desorption. The study on the effect of different monomers copolymerised with hydroxyethyl methacrylate (HEMA) on the protein up-take showed that monomers producing a positive charge on the copolymer can reduce the spoilation with lysozyme. The studies were extended to real cases in order to compare the patient dependent factors. The in-vivo studies showed that the spoilation is patient dependent as well as other factors. Studies on the extrinsic factors such as dye used in colour lenses showed that the addition of colourant affects protein absorption and, in one case, its effect is beneficial to the wearer as it reduces the quantity of the protein absorbed.

EU governance of the internet:analyzing Europol’s role in the development of a EU cyber crime and cyber security policies

In recent years, the European Union has come to view cyber security, and in particular, cyber crime as one of the most relevant challenges to the completion of its Area of Freedom, Security and Justice. Given European societies’ increased reliance on borderless and decentralized information technologies, this sector of activity has been identified as an easy target for actors such as organised criminals, hacktivists or terrorist networks. Such analysis has been accompanied by EU calls to step up the fight against unlawful online activities, namely through increased cooperation among law enforcement authorities (both national and extra- communitarian), the approximation of legislations, and public- private partnerships. Although EU initiatives in this field have, so far, been characterized by a lack of interconnection and an integrated strategy, there has been, since the mid- 2000s, an attempt to develop a more cohesive and coordinated policy. An important part of this policy is connected to the activities of Europol, which have come to assume a central role in the coordination of intelligence gathering and analysis of cyber crime. The European Cybercrime Center (EC3), which will become operational within Europol in January 2013, is regarded, in particular, as a focal point of the EU’s fight against this phenomenon. Bearing this background in mind, the present article wishes to understand the role of Europol in the development of a European policy to counter the illegal use of the internet. The article proposes to reach this objective by analyzing, through the theoretical lenses of experimental governance, the evolution of this agency’s activities in the area of cyber crime and cyber security, its positioning as an expert in the field, and the consequences for the way this policy is currently developing and is expected to develop in the near future.