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.

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.

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.

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.

The effects of negative affectivity on self-reported activity limitations in stroke patients:testing the symptom perception, disability and psychosomatic hypotheses

This study investigated whether Negative Affectivity (NA) causes bias in self-report measures of activity limitations or whether NA has a real, non-artifactual association with activity limitations. The Symptom Perception Hypothesis (NA negatively biases self-reporting), Disability Hypothesis (activity limitations cause NA) and Psychosomatic Hypothesis (NA causes activity limitations) were examined longitudinally using both self-report and objective activity limitations measures. Participants were 101 stroke patients and their caregivers interviewed within two weeks of discharge, six weeks later and six months post-discharge. NA and self-report, proxy-report and observed performance activity (walking) limitations were assessed at each interview. NA was associated with activity limitations across measures. Both the Disability and Psychosomatic Hypotheses were supported: initial NA predicted objective activity limitations at six weeks but, additionally, activity limitations at six weeks predicted NA at six months. These results suggest that NA both affects and is affected by activity limitations and does not simply influence reporting.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

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.

Astigmatism and vision:should all astigmatism always be corrected?

As technology and medical devices improve, there is much interest in when and how astigmatism should be corrected with refractive surgery. Astigmatism can be corrected by most forms of refractive surgery, such as using excimer lasers algorithms to ablate the cornea to compensate for the magnitude of refractive error in different meridians. Correction of astigmatism at the time of cataract surgery is well developed and can be achieved through incision placement, relaxing incisions and toric intraocular lens (IOL) implantation. This was less of an issue in the past when there was a lower expectation to be spectacle independent after cataract surgery, in which case the residual refractive error, including astigmatism, could be compensated for with spectacle lenses. The issue of whether presurgical astigmatism should be corrected can be considered separately depending on whether a patient has residual accommodation, and the type of refractive surgery under consideration. We have previously reported on the visual impact of full correction of astigmatism, rather than just correcting the mean spherical equivalent. Correction of astigmatism as low as 1.00 dioptres significantly improves objective and subjective measures of functional vision in prepresbyopes at distance and near.

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.

A survey based analysis of IT adoption and 3PLs' performance

Purpose: In today's competitive scenario, effective supply chain management is increasingly dependent on third-party logistics (3PL) companies' capabilities and performance. The dissemination of information technology (IT) has contributed to change the supply chain role of 3PL companies and IT is considered an important element influencing the performance of modern logistics companies. Therefore, the purpose of this paper is to explore the relationship between IT and 3PLs' performance, assuming that logistics capabilities play a mediating role in this relationship. Design/methodology/approach: Empirical evidence based on a questionnaire survey conducted on a sample of logistics service companies operating in the Italian market was used to test a conceptual resource-based view (RBV) framework linking IT adoption, logistics capabilities and firm performance. Factor analysis and ordinary least square (OLS) regression analysis have been used to test hypotheses. The focus of the paper is multidisciplinary in nature; management of information systems, strategy, logistics and supply chain management approaches have been combined in the analysis. Findings: The results indicate strong relationships among data gathering technologies, transactional capabilities and firm performance, in terms of both efficiency and effectiveness. Moreover, a positive correlation between enterprise information technologies and 3PL financial performance has been found. Originality/value: The paper successfully uses the concept of logistics capabilities as mediating factor between IT adoption and firm performance. Objective measures have been proposed for IT adoption and logistics capabilities. Direct and indirect relationships among variables have been successfully tested. © Emerald Group Publishing Limited.

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Changes in ocular physiology, tear film characteristics, and symptomatology with 18 months silicone hydrogel contact lens wear

Purpose. The purpose of this study was to evaluate the longitudinal changes in ocular physiology, tear film characteristics, and symptomatology experienced by neophyte silicone hydrogel (SiH) contact lens wearers in a daily-wear compared with a continuous-wear modality and with the different commercially available lenses over an 18-month period. Methods. Forty-five neophyte subjects were enrolled in the study and randomly assigned to wear one of two SiH materials: lotrafilcon A or balafilcon A lenses on either a daily- (LDW; BDW) or continuous-wear (LCW; BCW) basis. Additionally, a group of noncontact lens-wearing subjects (control group) was also recruited and followed over the same study period. Objective and subjective grading of ocular physiology were carried out together with tear meniscus height (TMH) and noninvasive tear breakup time (NITBUT). Subjects also subjectively rated symptoms and judgments with lens wear. After initial screening, subsequent measurements were taken after 1, 3, 6, 12, and 18 months. Results. Subjective and objective grading of ocular physiology revealed a small increase in bulbar, limbal, and palpebral hyperemia as well as corneal staining over time with both lens materials and regimes of wear (p < 0.05). No significant changes in NITBUT or TMH were found (p > 0.05). Subjective symptoms and judgment were not material- or modality-specific. Conclusions. Daily and continuous wear of SiH contact lenses induced small but statistically significant changes in ocular physiology and symptomatology. Clinical measures of tear film characteristics were unaffected by lens wear. Both materials and regimes of wear showed similar clinical performance. Long-term SiH contact lens wear is shown to be a successful option for patients. Copyright © 2006 American Academy of Optometry.

Leader‐Member Exchange (LMX) and performance:a meta‐analytic review

This paper reports a meta-analysis that examines the relationship between leader-member exchange (LMX) relationship quality and a multidimensional model of work performance (task, citizenship, and counterproductive performance). The results show a positive relationship between LMX and task performance (146 samples, ρ = .30) as well as citizenship performance (97 samples, ρ = .34), and negatively with counterproductive performance (19 samples, ρ = -.24). Of note, there was a positive relationship between LMX and objective task performance (20 samples, ρ = .24). Trust, motivation, empowerment, and job satisfaction mediated the relationship between LMX and task and citizenship performance with trust in the leader having the largest effect. There was no difference due to LMX measurement instrument (e.g., LMX7, LMX-MDM). Overall, the relationship between LMX and performance was weaker when (a) measures were obtained from a different source or method and (b) LMX was measured by the follower than the leader (with common source- and method-biased effects stronger for leader-rated LMX quality). Finally, there was evidence for LMX leading to task performance but not for reverse or reciprocal directions of effects.

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.