Visual comparison of multifocal contact lens to monovision

Purpose. To compare visual function with the Bausch & Lomb PureVision multifocal contact lens to monovision with PureVision single vision contact lenses. Methods. Twenty presbyopic subjects were fitted with either the PureVision multifocal contact lens or monovision with PureVision singlevision lenses. Aftera 1-month trial, the following assessments of visual function were made: (a) distance, intermediate, and near visual acuity (VA); (b) reading ability; (c) distance and near contrast sensitivity function (CSF); (d) near range of clear vision; (e) stereoacuity; and (f) subjective evaluation of near vision ability with a standardized questionnaire. Subjects were then refitted with the alternative correction and the procedure was repeated. All measurements were compared between the two corrections, whereas the ``low addition'' multifocal lens was also compared with the ``high addition'' alternative. Results. Distance and near VA were significantly better with monovision than with the multifocal option (p < 0.05). Intermediate VA (p = 0.13) was similar with both corrections, whereas there was also no significant difference in distance and near CSF (p = 0.29 on both occasions). Reading speeds (p = 0.48) and the critical print size (p = 0.90) were not significantly different between the two contact lens corrections, but stereoacuity (p < 0.01) and the near range of clear vision (p < 0.05) were significantly better with the multifocal option than with monovision. Subjective assessment of near ability was similar for both types of contact lens (p = 0.52). The high addition multifocal lens produced significantly poorer distance and near CSF, near VA, and critical print size compared with the low addition alternative. Conclusions. Monovision performed better than a center-near aspheric simultaneous vision multifocal contact lens of the same material for distance and near VA only. The multifocal option provides better stereoacuity and near range of clear vision, with little differences in CSF, so a better balance of real-world visual function may be achieved due to minimal binocular disruption. (Optom Vis Sci 2009;86:98-105)

The effect of intraocular scattered light on the contrast sensitivity function

Intraocular light scatter is high in certain subject groups eg the elderly, due to increased optical media turbidity, which scatters and attenuates light travelling towards the retina. This causes reduced retinal contrast especially in the presence of glare light. Such subjects have depressed Contrast Sensitivity Functions (CSF). Currently available clinical tests do not effectively reflect this visual disability. Intraocular light scatter may be quantified by measuring the CSF with and without glare light and calculating Light Scatter Factors (LSF). To record the CSF on clinically available equipment (Nicolet CS2000), several psychophysical measurement techniques were investigated, and the 60 sec Method of Increasing Contrast was selected as the most appropriate. It was hypothesised that intraocular light scatter due to particles of different dimensions could be identified by glare sources at wide (30°) and narrow (3.5°) angles. CSFs andLSFs were determined for: (i) Subjects in young, intermediate and old age groups. (ii) Subjects during recovery from large amounts of induced corneal oedema. (iii) A clinical sample of contact lens (CL) wearers with a group of matched controls. The CSF was attenuated at all measured spatial frequencies with the intermediate and old group compared to the young group. High LSF values were found only in the old group (over 60 years). It was concluded that CSF attenuation in the intermediate group was due to reduced pupil size, media absorption and/or neural factors. In the old group, the additional factor was high intraocular light scatter levels of lenticular origin. The rate of reduction of the LSF for the 3.5° glare angle was steeper than that for the 30° angle, following induced corneal oedema. This supported the hypothesis, as it was anticipated that epithelial oedema would recover more rapidly than stromal oedema. CSFs and LSFs were markedly abnormal in the CL wearers. The analytical details and the value of these investigative techniques in contact lens research are discussed.

Mechanisms contributing to the enhanced respiratory burst of neutrophils observed in periodontitis

The aim of this thesis is to investigate possible mechanisms that may contribute to neutrophil hyperactivity and hyper-reactivity. One possibility is the presence of a neutrophil priming factors within the peripheral circulation of periodontitis patients. To examine this possibility differentiated HL-60 cells and primary neutrophils were studied in the presence and absence of plasma from periodontitis patients. In independent experiments, plasma was depleted of IL-8, GM-CSF, interferon-a, immunoglobulins and albumin. This work demonstrated that plasma factors such as IL-8, GM-CSF, and interferon-a present during periodontitis may contribute towards the reported hyperactive neutrophil phenotype. Furthermore, this work demonstrated that products from Pg may regulate neutrophil accumulation at infected periodontal sites by promoting gingipain-dependent modification of IL-8-77 into a more biologically active chemokine. To elucidate whether the oxidatively stressed environment that neutrophils are exposed to in periodontitis could influence hyperactivity and hyper-reactivity, neutrophils were depleted of glutathione. This work showed that during oxidative stress, where cellular redox-levels have been altered, neutrophils exhibit an increased respiratory burst. In conclusion, this work highlights the multiple mechanisms that may contribute to neutrophil hyperactivity and hyperreactivity including gingipain-modulated activity of IL-8 variants, the effect of host factors such as IL-8, GM-CSF, interferon-a on neutrophils priming and activation, and the shift of neutrophil GSH:GSSG ratio in favour of a more oxidised environment as observed in periodontitis.

Activation of the neutrophil respiratory burst by plasma from periodontitis patients is mediated by pro-inflammatory cytokines

Aim: To determine the effect of periodontitis patients' plasma on the neutrophil oxidative burst and the role of albumin, immunoglobulins (Igs) and cytokines. Materials and Methods: Plasma was collected from chronic periodontitis patients (n=11) and periodontally healthy controls (n=11) and used with/without depletion of albumin and Ig or antibody neutralization of IL-8, GM-CSF or IFN-a to prime/stimulate peripheral blood neutrophils, isolated from healthy volunteers. The respiratory burst was measured by lucigenin-dependent chemiluminescence. Plasma cytokine levels were determined by ELISA. Results: Plasmas from patients were significantly more effective in both directly stimulating neutrophil superoxide production and priming for subsequent formyl-met-leu-phe (fMLP)-stimulated superoxide production than plasmas from healthy controls (p<0.05). This difference was maintained after depletion of albumin and Ig. Plasma from patients contained higher mean levels of IL-8, GM-CSF and IFN-a. Individual neutralizing antibodies against IL-8, GM-CSF or IFN-a inhibited the direct stimulatory effect of patients' plasma, whereas the ability to prime for fMLP-stimulated superoxide production was only inhibited by neutralization of IFN-a. The stimulating and priming effects of control plasma were unaffected by antibody neutralization. Conclusions: This study demonstrates that plasma cytokines may have a role in inducing the hyperactive (IL-8, GM-CSF, IFN-a) and hyper-reactive (IFN-a) neutrophil phenotype seen in periodontitis patients.

Development of a physiologically-based pharmacokinetic model of the rat central nervous system

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

Source localization methods

One of the most pressing demands on electrophysiology applied to the diagnosis of epilepsy is the non-invasive localization of the neuronal generators responsible for brain electrical and magnetic fields (the so-called inverse problem). These neuronal generators produce primary currents in the brain, which together with passive currents give rise to the EEG signal. Unfortunately, the signal we measure on the scalp surface doesn't directly indicate the location of the active neuronal assemblies. This is the expression of the ambiguity of the underlying static electromagnetic inverse problem, partly due to the relatively limited number of independent measures available. A given electric potential distribution recorded at the scalp can be explained by the activity of infinite different configurations of intracranial sources. In contrast, the forward problem, which consists of computing the potential field at the scalp from known source locations and strengths with known geometry and conductivity properties of the brain and its layers (CSF/meninges, skin and skull), i.e. the head model, has a unique solution. The head models vary from the computationally simpler spherical models (three or four concentric spheres) to the realistic models based on the segmentation of anatomical images obtained using magnetic resonance imaging (MRI). Realistic models – computationally intensive and difficult to implement – can separate different tissues of the head and account for the convoluted geometry of the brain and the significant inter-individual variability. In real-life applications, if the assumptions of the statistical, anatomical or functional properties of the signal and the volume in which it is generated are meaningful, a true three-dimensional tomographic representation of sources of brain electrical activity is possible in spite of the ‘ill-posed’ nature of the inverse problem (Michel et al., 2004). The techniques used to achieve this are now referred to as electrical source imaging (ESI) or magnetic source imaging (MSI). The first issue to influence reconstruction accuracy is spatial sampling, i.e. the number of EEG electrodes. It has been shown that this relationship is not linear, reaching a plateau at about 128 electrodes, provided spatial distribution is uniform. The second factor is related to the different properties of the source localization strategies used with respect to the hypothesized source configuration.