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 clinical performance of ‘comfort-enhanced' daily disposable soft contact lenses

Purpose: To examine the objective clinical performance of ‘comfort-enhanced’ daily disposable contact lenses over a 16-h day. Methods: Four contact lenses (Hilafilcon B, Etafilcon A Plus, Nelfilcon A and Nelfilcon A Plus) were evaluated in an investigator masked, open label trial at the end of a week’s bilateral wear. Pre-lens noninvasive tear break-up time (PL-NITBUT), tear prism height, bulbar hyperaemia and ocular surface temperature (OST) were measured with the lens in situ at 8, 12 and 16 h of wear. Results: There was no difference between how many hours the lenses types were worn each day (F = 0.90, p = 0.44). The PL-NITBUT decreased with the duration of daily lens wear (F = 32.0, p < 0.001) and was more stable with Nelfilcon A Plus (F = 6.00, p = 0.002) than with the other lenses evaluated. Bulbar blood vessels increased in coverage (F = 11.5, p < 0.001) but not overall redness (F = 0.0, p = 0.99) with the duration of daily lens wear, but there was no difference between the lenses (p > 0.05). The tear prism height decreased with the duration of daily wear (F = 27.0, p < 0.001) and differed between lenses (F = 2.9, p = 0.04). The OST decreased with the duration of lens wear (F = 119.7, p < 0.001) and was reduced by daily disposable lens wear (F = 7.88, p < 0.001), but did not differ between lenses (F = 0.88, p = 0.45). Conclusions: Objective measures of tear film indicated a difference between the lenses evaluated for PLNITBUT and tear prism height, but not for wearing time or bulbar conjunctival hyperaemia. Therefore clinical benefits of daily disposable ‘comfort enhancing’ contact lenses can be measured, but challenges remain in producing contact lenses that do not compromise anterior eye physiology over the whole day. 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

On the validity of subjective measures of company performance

Subjective measures of company performance are widely used in research and typically are interpreted as equivalent to objective measures. Yet, the assumption of equivalence is open to challenge. We compared the use of both types of measure in 3 separate samples. Findings were consistent in showing that: (a) subjective and objective measures of company performance were positively associated (convergent validity); (b) those relationships were stronger than those between measures of differing aspects of performance using the same method (discriminant validity); and (c) the relationships of subjective and objective company performance measures with a range of independent variables were equivalent (construct validity).

Objective methods for anterior ocular grading

This thesis set out to develop an objective analysis programme that correlates with subjective grades but has improved sensitivity and reliability in its measures so that the possibility of early detection and reliable monitoring of changes in anterior ocular surfaces (bulbar hyperaemia, palpebral redness, palpebral roughness and corneal straining) could be increased. The sensitivity of the program was 20x greater than subjective grading by optometrists. The reliability was found to be optimal (r=1.0) with subjective grading up to 144x more variable (r=0.08). Objective measures were used to create formulae for an overall ‘objective-grade’ (per surface) equivalent to those displayed by the CCLRU or Efron scales. The correlation between the formulated objective verses subjective grades was high, with adjusted r2 up to 0.96. Determination of baseline levels of objective grade were investigated over four age groups (5-85years n= 120) so that in practice a comparison against the ‘normal limits’ could be made. Differences for bulbar hyperaemia were found between the age groups (p<0.001), and also for palpebral redness and roughness (p<0.001). The objective formulae were then applied to the investigation of diurnal variation in order to account for any change that may affect the baseline. Increases in bulbar hyperaemia and palpebral redness were found between examinations in the morning and evening. Correlation factors were recommended. The program was then applied to clinical situations in the form of a contact lens trial and an investigation into iritis and keratoconus where it successfully recognised various surface changes. This programme could become a valuable tool, greatly improving the chances of early detection of anterior ocular abnormalities, and facilitating reliable monitoring of disease progression in clinical as well as research environments.

The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia - an exploratory study

Aims - To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP). Methods - A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire. Results - Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing “carelessness at times about taking medication” as the primary reason for non-adherence followed by “forgetting to take the medication” (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored ≥ 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P < 0.05). Conclusions - The present study explored various ways to assess adherence rates to thiopurine medication in ALL patients and highlighted the importance of combining both objective and subjective measures as a better way to assess adherence to oral thiopurines.

Objective analysis of contact lens fit

Purpose: To assess the validity and repeatability of objective compared to subjective contact lens fit analysis. Methods: Thirty-five subjects (aged 22.0. ±. 3.0 years) wore two different soft contact lens designs. Four lens fit variables: centration, horizontal lag, post-blink movement in up-gaze and push-up recovery speed were assessed subjectively (four observers) and objectively from slit-lamp biomicroscopy captured images and video. The analysis was repeated a week later. Results: The average of the four experienced observers was compared to objective measures, but centration, movement on blink, lag and push-up recovery speed all varied significantly between them (p <. 0.001). Horizontal lens centration was on average close to central as assessed both objectively and subjectively (p > 0.05). The 95% confidence interval of subjective repeatability was better than objective assessment (±0.128. mm versus ±0.168. mm, p = 0.417), but utilised only 78% of the objective range. Vertical centration assessed objectively showed a slight inferior decentration (0.371. ±. 0.381. mm) with good inter- and intrasession repeatability (p > 0.05). Movement-on-blink was lower estimated subjectively than measured objectively (0.269. ±. 0.179. mm versus 0.352. ±. 0.355. mm; p = 0.035), but had better repeatability (±0.124. mm versus ±0.314. mm 95% confidence interval) unless correcting for the smaller range (47%). Horizontal lag was lower estimated subjectively (0.562. ±. 0.259. mm) than measured objectively (0.708. ±. 0.374. mm, p <. 0.001), had poorer repeatability (±0.132. mm versus ±0.089. mm 95% confidence interval) and had a smaller range (63%). Subjective categorisation of push-up speed of recovery showed reasonable differentiation relative to objective measurement (p <. 0.001). Conclusions: The objective image analysis allows an accurate, reliable and repeatable assessment of soft contact lens fit characteristics, being a useful tool for research and optimisation of lens fit in clinical practice.

Visual function and subjective quality of life compared in subjects with acquired macular disease

PURPOSE: To determine the objective measures of visual function that are most relevant to subjective quality of vision and perceived reading ability in patients with acquired macular disease. METHODS: Twenty-eight patients with macular disease underwent a comprehensive assessment of visual function. The patients also completed a vision-related quality-of-life questionnaire that included a section of general questions about perceived visual performance and a section with specific questions on reading. RESULTS: Results of all tests of vision correlated highly with reported vision-related quality-of-life impairment. Low-contrast tests explained most of the variance in self-reported problems with reading. Text-reading speed correlated highly with overall concern about vision. CONCLUSIONS: Reading performance is strongly associated with vision-related quality of life. High-contrast distance acuity is not the only relevant measure of visual function in relation to the perceived visual performance of a patient with macular disease. The results suggest the importance of print contrast, even over print size, in reading performance in patients with acquired macular disease.

The role of self-regulation as a meta-competency in developing leaders: a longitudinal field experimental study

The question of how to develop leaders so that they are more effective in a variety of situations, roles and levels has inspired a voluminous amount of research. While leader development programs such as executive coaching and 360-degree feedback have been widely practiced to meet this demand within organisations, the research in this area has only scratched the surface. Drawing from the past literature and leadership practices, the current research conceptualised self-regulation, as a metacompetency that would assist leaders to further develop the specific competencies needed to perform effectively in their leadership role, leading to an increased rating of leader effectiveness and to enhanced group performance. To test this conceptualisation, a longitudinal field experimental study was conducted across ten months with a pre- and two post-test intervention designs with a matched control group. This longitudinal field experimental compared the difference in leader and team performance after receiving self-regulation intervention that was delivered by an executive coach. Leaders in experimental group also received feedback reports from 360-degree feedback at each stage. Participants were 40 leaders, 155 followers and 8 supervisors. Leaders’ performance was measured using a multi-source perceptual measure of leader performance and objective measures of team financial and assessment performance. Analyses using repeated measure of ANCOVA on pre-test and two post-tests responses showed a significant difference between leader and team performance between experimental and control group. Furthermore, leader competencies mediated the relationship between self-regulation and performance. The implications of these findings for the theory and practice of leadership development training programs and the impact on organisational performance are discussed.

Autonomic correlates of ocular accommodation and cardiovascular function

PURPOSE: To evaluate the hypothesis that objective measures of open- and closed-loop ocular accommodation are related to systemic cardiovascular function, and ipso facto autonomic nervous system activity. METHODS: Sixty subjects (29 male; 31 female) varying in age from 18 to 33 years (average: 20.3 +/- 2.9 years) with a range of refractive errors [mean spherical equivalent (MSE): -7.12 to +1.82 D] participated in the study. Five 20-s continuous objective recordings of the accommodative response, measured with an open-view IR autorefractor (Shin-Nippon SRW-5000), were obtained for a variety of open- and closed-loop accommodative demands while simultaneous continuous measurement of heart rate was recorded with a finger-mounted piezo-electric pulse transducer for 5 min. Fast Fourier Transformation of cardiovascular function allowed the absolute and relative power of the autonomic components to be assessed in the frequency-domain, whereas heart period gave an indication of the time-domain response. RESULTS: Increasing closed-loop accommodative demand led to a concurrent increase in heart rate of approximately 2 beats/min for a 4.0 D increase in accommodative demand. The increase was attributable to a reduction in the absolute (p < 0.05) and normalised (p < 0.001) input of the systemic parasympathetic nervous system, and was unaffected by refractive group. The interaction with refractive group failed to reach significance. CONCLUSIONS: For sustained accommodation effort, the data demonstrate covariation between the oculomotor and cardiovascular systems which implies that a near visual task can significantly influence cardiovascular behaviour. Accommodative effort alone, however, is not a sufficient stimulus to induce autonomic differences between refractive groups. The data suggest that both the oculomotor and cardiovascular systems are predominantly attributable to changes in the systemic parasympathetic nervous system.

Clinical evaluation of the Grand Seiko Auto Ref/Keratometer WAM-5500

Purpose: A clinical evaluation of the Grand Seiko Auto Ref/Keratometer WAM-5500 (Japan) was performed to evaluate validity and repeatability compared with non-cycloplegic subjective refraction and Javal–Schiotz keratometry. An investigation into the dynamic recording capabilities of the instrument was also conducted. Methods: Refractive error measurements were obtained from 150 eyes of 75 subjects (aged 25.12 ± 9.03 years), subjectively by a masked optometrist, and objectively with the WAM-5500 at a second session. Keratometry measurements from the WAM-5500 were compared to Javal–Schiotz readings. Intratest variability was examined on all subjects, whilst intertest variability was assessed on a subgroup of 44 eyes 7–14 days after the initial objective measures. The accuracy of the dynamic recording mode of the instrument and its tolerance to longitudinal movement was evaluated using a model eye. An additional evaluation of the dynamic mode was performed using a human eye in relaxed and accommodated states. Results: Refractive error determined by the WAM-5500 was found to be very similar (p = 0.77) to subjective refraction (difference, -0.01 ± 0.38 D). The instrument was accurate and reliable over a wide range of refractive errors (-6.38 to +4.88 D). WAM-5500 keratometry values were steeper by approximately 0.05 mm in both the vertical and horizontal meridians. High intertest repeatability was demonstrated for all parameters measured: for sphere, cylinder power and MSE, over 90% of retest values fell within ±0.50 D of initial testing. In dynamic (high-speed) mode, the root-mean-square of the fluctuations was 0.005 ± 0.0005 D and a high level of recording accuracy was maintained when the measurement ring was significantly blurred by longitudinal movement of the instrument head. Conclusion: The WAM-5500 Auto Ref/Keratometer represents a reliable and valid objective refraction tool for general optometric practice, with important additional features allowing pupil size determination and easy conversion into high-speed mode, increasing its usefulness post-surgically following accommodating intra-ocular lens implantation, and as a research tool in the study of accommodation.

Data analysis methods in optometry Part 8: Principal components analysis (PCA) and factor analysis (FA)

PCA/FA is a method of analyzing complex data sets in which there are no clearly defined X or Y variables. It has multiple uses including the study of the pattern of variation between individual entities such as patients with particular disorders and the detailed study of descriptive variables. In most applications, variables are related to a smaller number of ‘factors’ or PCs that account for the maximum variance in the data and hence, may explain important trends among the variables. An increasingly important application of the method is in the ‘validation’ of questionnaires that attempt to relate subjective aspects of a patients experience with more objective measures of vision.

Accessibility, deprivation and rural planning policies.

Since the Second World War a range of policies have been implemented by central and local government agencies, with a view to improving accessibility to facilities, housing and employment opportunities within rural areas. It has been suggested that a lack of reasonable access to a range of such facilities and opportunities constitutes a key aspect of deprivation or disadvantage for rural residents. Despite considerable interest, very few attempts have been made to assess the nature and incidence of this disadvantage or the reaction of different sections of the population of rural areas to it. Moreover, almost all previous assessments have relied on so-called 'objective' measures of accessibility and disadvantage and failed to consider the relationship between such measures and 'subjective' measures such as individual perceptions. It is this gap in knowledge that the research described in this thesis has addressed. Following a critical review of relevant literature the thesis describes the way in which data on 'objective' and 'subjective' indicators of accessibility and behavioural responses to accessibility problems was collected, in six case study areas in Shropshire. Analysis of this data indicates that planning and other government policies have failed to significantly improve rural resident's accessibility to their basic requirements, and may in some cases have exacerbated it, and that as a result certain sections of the rural population are relatively disadvantaged. Moreover, analysis shows that .certain aspects of individual subjective' assessments of such accessibility disadvantage are significantly associated with more easily-obtained 'objective' measures. By using discriminant analysis the research demonstrates that it is possible to predict the likely levels of satisfaction with access to facilities from a range of 'objective' measures. The research concludes by highlighting the potential practical applications of such indicators in policy formulation, policy appraisal and policy evaluation.

Synkinesis of accommodation and vergence during sustained rear vision

It is well established that a synkinetic relationship exists between the accommodation and vergence components of the oculomotor near response such that increased accommodation will initiate a vergence response (i.e. accommodative convergence) and conversely increased vergence will drive accommodation (i.e. convergent accommodation) . The synkinesis associated with sustained near-vision was examined in a student population consisting of emmetropes, late-onset myopes (LOMs) i.e. myopia onset at 15 years of age or later and early-onset myopes (EOMs) i.e. myopia onset prior to 15 years of age. Oculomotor synkinesis was investigated both under closed-loop conditions and with either accommodation or vergence open-loop. Objective measures of the accommodative response were made using an infra-red optometer. Differences in near-response characteristics were observed between LOMs and EOMs under both open- and closed-loop conditions. LOMs exhibit significantly higher levels of disparity-induced accommodation (accommodation driven by vergence under closed-loop conditions) and lower response accommodative convergence/accommodation (AC/A) ratios when compared with EOMs. However no difference in convergent accommodation/convergence (CA/C) ratios were found between the three refractive groups. Accommodative adaptation was examined by comparing the pre- to post-task shift in dark focus (DF) following near-vision tasks. Accommodative adaptation was observed following tasks as brief as 15s. Following a 45s near-vision task, subjects having pre-task DF greater than +0.750 exhibited a marked negative shift in post-task DF which was shown to be induced by beta-adrenergic innervation to the ciliary muscle. However no evidence was found to support the proposal of reduced adrenergic innervation to the ciliary muscle in LOMs. Disparity-vergence produced a reduction in accommodative adaptation suggesting that oculomotor adaptation was not driven by the output of the near-response crosslinks. In order to verify this proposition, the effect of vergence adaptation on CA/C was investigated and it was observed that prism adaptation produced no significant change in the CA/C ratio. This would indicate that in a model of accommodation-vergence interaction, the near response cross-links occur after the input to the adaptive components of the oculomotor response rather than before the adaptive elements as reported in previous literature. The findings of this thesis indicate differences in the relative composition of the aggregate accommodation and vergence responses in the three refractive groups examined. They may also have implications with regard to the aetiology of late-onset myopia.

Optimising the clinical analysis of retinal image quality in the human eye

Visual perception is dependent on both light transmission through the eye and neuronal conduction through the visual pathway. Advances in clinical diagnostics and treatment modalities over recent years have increased the opportunities to improve the optical path and retinal image quality. Higher order aberrations and retinal straylight are two major factors that influence light transmission through the eye and ultimately, visual outcome. Recent technological advancements have brought these important factors into the clinical domain, however the potential applications of these tools and considerations regarding interpretation of data are much underestimated. The purpose of this thesis was to validate and optimise wavefront analysers and a new clinical tool for the objective evaluation of intraocular scatter. The application of these methods in a clinical setting involving a range of conditions was also explored. The work was divided into two principal sections: 1. Wavefront Aberrometry: optimisation, validation and clinical application The main findings of this work were: • Observer manipulation of the aberrometer increases variability by a factor of 3. • Ocular misalignment can profoundly affect reliability, notably for off-axis aberrations. • Aberrations measured with wavefront analysers using different principles are not interchangeable, with poor relationships and significant differences between values. • Instrument myopia of around 0.30D is induced when performing wavefront analysis in non-cyclopleged eyes; values can be as high as 3D, being higher as the baseline level of myopia decreases. Associated accommodation changes may result in relevant changes to the aberration profile, particularly with respect to spherical aberration. • Young adult healthy Caucasian eyes have significantly more spherical aberration than Asian eyes when matched for age, gender, axial length and refractive error. Axial length is significantly correlated with most components of the aberration profile. 2. Intraocular light scatter: Evaluation of subjective measures and validation and application of a new objective method utilising clinically derived wavefront patterns. The main findings of this work were: • Subjective measures of clinical straylight are highly repeatable. Three measurements are suggested as the optimum number for increased reliability. • Significant differences in straylight values were found for contact lenses designed for contrast enhancement compared to clear lenses of the same design and material specifications. Specifically, grey/green tints induced significantly higher values of retinal straylight. • Wavefront patterns from a commercial Hartmann-Shack device can be used to obtain objective measures of scatter and are well correlated with subjective straylight values. • Perceived retinal stray light was similar in groups of patients implanted with monofocal and multi focal intraocular lenses. Correlation between objective and subjective measurements of scatter is poor, possibly due to different illumination conditions between the testing procedures, or a neural component which may alter with age. Careful acquisition results in highly reproducible in vivo measures of higher order aberrations; however, data from different devices are not interchangeable which brings the accuracy of measurement into question. Objective measures of intraocular straylight can be derived from clinical aberrometry and may be of great diagnostic and management importance in the future.

Environmental quality in residential areas : a social survey approach to improvement priorities

The research is concerned with the measurement of residents' evaluations of the environmental quality of residential areas. The research reflects the increased attention being given to residents' values in planning decisions affecting the residential environment. The work was undertaken in co-operation with a local authority which was in the process of revising its housing strategy, and in particular the priorities for improvement action. The study critically examines the existing evidence on environmental values and their relationship to the environment and points to a number of methodological and conceptual deficiencies. The research strategy developed on the basis of the research review was constrained by the need to keep any survey methods simple so that they could easily be repeated, when necessary, by the sponsoring authority. A basic perception model was assumed, and a social survey carried out to measure residents' responses to different environmental conditions. The data was only assumed to have ordinal properties, necessitating the extensive use of non-parametric statistics. Residents' expressions of satisfaction with the component elements of the environment (ranging from convenience to upkeep and privacy) were successfully related to 'objective' measures of the environment. However the survey evidence did not justify the use of the 'objective' variables as environmental standards. A method of using the social survey data directly as an aid to decision-making is discussed. Alternative models of the derivation of overall satisfaction with the environment are tested, and the values implied by the additive model compared with residents' preferences as measured directly in the survey. Residents' overall satisfactions with the residential environment were most closely related to their satisfactions with the "Appearance" and the "Reputation" of their areas. By contrast the most important directly measured preference was "Friendliness of area". The differences point to the need to define concepts used in social research clearly in operational terms, and to take care in the use of values 'measured' by different methods.