Physiological and pathological human ocular perfusion characteristics

There were three principle aims to this thesis. Firstly, the acquisition protocols of clinical blood flow apparatus were investigated in order to optimise them for both cross-sectional and longitudinal application. Secondly, the effects of physiological factors including age and systematic circulation on ocular blood flow were investigated. Finally, the ocular perfusion characteristics of patients diagnosed with ocular diseases considered to be of a vascular origin were investigated. The principle findings of this work are:- 1) Optimisation of clinical investigationsPhotodiode sensitivity of the scanning laser Doppler flowmeter should be kept within a range of 70-150 DC when acquiring images of the retina and optic nerve head in order to optimise the reproducibility of capillary blood flow measures. Account of the physiological spatial variation in retinal blood flow measures can be made using standard analysis protocols of the scanning laser Doppler flowmeter combined with a local search strategy. Measurements of pulsatile ocular blood flow using the ocular blood flow analyser are reproducible, however this reproducibility can be improved when consecutive intraocular pressure pulses are used to calculate pulsatile ocular blood flow. Spectral analysis of the intraocular pressure pulse-wave is viable and identifies the first four harmonic components of the waveform. 2) Physiological variation in ocular perfusionAge results in a significant reduction in perfusion of the retinal microcirculation, which is not evident in larger vessel beds such as the choroid. Despite known asymmetry in the systemic vasculature, no evidence of interocular asymmetry in ocular perfusion is apparent. 3) Pathological variation in ocular perfusionIn primary open angle glaucoma, perfusion is reduced in the retinal microcirculation of patients classified as having early to moderate visual field defects. However, ocular pulsatility defects are masked when patients and subjects are matched for systemic variables (pulse rate and mean arterial pressure); differentiation is facilitated by the application of waveform analysis to the continuos intraocular pressure curve even in the early stages of disease. Diabetic patients with adequate glycaemic control, exhibit maintenance of macular blood flow, macular topography and visual function following phacoemulsification.

Retinal and systemic vascular function in health and disease: the effect of smoking and coronary artery disease

The purpose of the following studies was to explore the effect of systemic vascular and endothelial dysfunction upon the ocular circulation and functionality of the retina. There are 6 principal sections to the present work. Retinal vessel activity in smokers and non-smokers: the principal findings of this work were: chronic smoking affects retinal vessel motion at baseline and during stimulation with flickering light; chronic smoking leads to a vaso-constrictory shift in retinal arteriolar reactivity to flicker; retinal arteriolar elasticity is decreased in chronic smokers. The effect of acute smoking on retinal vessel dynamics in smokers and non-smokers: the principal finding of this work was that retinal reactivity in chronic smokers is blunted when exposed to clicker light provocation immediately after smoking one cigarette. Ocular blood flow in coronary artery disease: The principal findings of this work were: retrobulbar and retinal blood flow is preserved in CAD patients, despite a change pulse wave transmission; arterial retinal response to flickering light provocation is significantly delayed in CAD patients; retinal venular diameters are significantly dilated in CAD patients. Autonomic nervous system function and peripheral circulation in CAD: The principal findings in this work were: CAD patients demonstrate a sympathetic overdrive during a 24 period; a delay in peripheral vascular reactivity (nail-fold capillaries) as observed in patients suffering from CAD could be caused by either arteriosclerotic changes of the vascular walls or due to systemic haemodynamic changes. Visual function in CAD: The principal findings in this work were: overall visual function in CAD patients is preserved, despite a decrease in contrast sensitivity; applying a filtering technique selecting those with greater coefficient of variance which in turn represents a decrease in reliability, some patients appear to have an impaired visual function as assessed using FDT visual field evaluation. Multiple functional, structural and biochemical vascular endothelial dysfunctions in patients suffering from CAD: relationships and possible implications: The principal findings of this work were: BMI significantly correlated with vWF (a marker of endothelial function) in CAD patients. Retinal vascular reactivity showed a significant correlation with peripheral reactivity parameters in controls which lacked in the CAD group and could reflect a loss in vascular endothelial integrity; visual field parameters as assessed by frequency doubling technology were strongly related with systemic vascular elasticity (ambulatory arterial stiffness index) in controls but not CAD patients.

Coexistence of macro- and micro-vascular abnormalities in newly diagnosed normal tension glaucoma patients

Purpose: To investigate the coexistence of ocular microvascular and systemic macrovascular abnormalities in early stage, newly diagnosed and previously untreated normal tension glaucoma patients (NTG). Methods: Retinal vascular reactivity to flickering light was assessed in 19 NTG and 28 age-matched controls by means of dynamic retinal vessel analysis (IMEDOS GmbH, Jena, Germany). Using a newly developed computational model, the entire dynamic vascular response profile to flicker light was imaged and used for analysis. In addition, assessments of carotid intima-media thickness (IMT) and pulse wave analysis (PWA) were conducted on all participants, along with blood pressure (BP) measurements and blood analyses for lipid metabolism markers. Results: Patients with NTG demonstrated an increased right and left carotid IMT (p = 0.015, p = 0.045) and an elevated PWA augmentation index (p = 0.017) in comparison with healthy controls, along with an enhanced retinal arterial constriction response (p = 0.028), a steeper retinal arterial constriction slope (p = 0.031) and a reduced retinal venous dilation response (p = 0.026) following flicker light stimulation. Conclusions: Early stage, newly diagnosed, NTG patients showed signs of subclinical vascular abnormalities at both macro- and micro-vascular levels, highlighting the need to consider multi-level circulation-related pathologies in the development and progression of this type of glaucoma.

Primary open-angle glaucoma vs normal-tension glaucoma:the vascular perspective

Objective: To compare and contrast the presence of ocular and systemic vascular function in newly diagnosed and previously untreated primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients with comparable, early stage, functional loss. Methods: The systemic vascular function of 19 POAG patients, 19 NTG patients and 20 healthy controls was assessed by means of 24 hour ambulatory blood pressure (ABPM), peripheral pulse wave analysis (PWA) and carotid intima-media thickness (IMT). Retinal vascular reactivity to flicker light was assessed using dynamic retinal vessel analysis (DVA,IMEDOS, GmbH, Jena, Germany). Results: When compared to normal controls, both POAG and NTG patients exhibited similarly increased nocturnal systemic blood pressure variability (p=0.011); peripheral arterial stiffness (p=0.015), carotid IMT (p=0.040) and reduced ocular perfusion pressure (OPP) (p<0.001). Furthermore, on DVA analysis, both groups of glaucoma patients also exhibited steeper retinal arterial constriction slopes (slope AC) following cessation of flicker (p=0.007) and a similarly increased fluctuation in arterial and venous baseline diameter (p=0.008 and p=0.009 respectively) in comparison to controls. Conclusion: POAG and NTG patients exhibit similar alterations in both ocular and systemic circulation at the early stages of their disease process. This highlights not only the importance of considering vascular risk factors in both conditions, but also raises questions about the current separation of the two conditions into completely distinct clinical entities.

Mode-locked fiber lasers with significant variability of generation regimes

We demonstrate a great variability of single-pulse (with only one pulse/wave-packet traveling along the cavity) generation regimes in fiber lasers passively mode-locked by non-linear polarization evolution (NPE) effect. Combining extensive numerical modeling and experimental studies, we identify multiple very distinct lasing regimes with a rich variety of dynamic behavior and a remarkably broad spread of key parameters (by an order of magnitude and more) of the generated pulses. Such a broad range of variability of possible lasing regimes necessitates developing techniques for control/adjustment of such key pulse parameters as duration, radiation spectrum, and the shape of the auto-correlation function. From a practical view point, availability of pulses/wave-packets with such different characteristics from the same laser makes it imperative to develop variability-aware designs with control techniques and methods to select appropriate application-oriented regimes. © 2014 The Authors.

Surface wave techniques for the study of engineering structures and materials

A wire drive pulse echo method of measuring the spectrum of solid bodies described. Using an 's' plane representation, a general analysis of the transient response of such solids has been carried out. This was used for the study of the stepped amplitude transient of high order modes of disks and for the case where there are two adjacent resonant frequencies. The techniques developed have been applied to the measurenent of the elasticities of refractory materials at high temperatures. In the experimental study of the high order in-plane resonances of thin disks it was found that the energy travelled at the edge of the disk and this initiated the work on one dimensional Rayleigh waves.Their properties were established for the straight edge condition by following an analysis similar to that of the two dimensional case. Experiments were then carried out on the velocity dispersion of various circuits including the disk and a hole in a large plate - the negative curvature condition.Theoretical analysis established the phase and group velocities for these cases and experimental tests on aluminium and glass gave good agreement with theory. At high frequencies all velocities approach that of the one dimensional Rayleigh waves. When applied to crack detection it was observed that a signal burst travelling round a disk showed an anomalous amplitude effect. In certain cases the signal which travelled the greater distance had the greater amplitude.An experiment was designed to investigate the phenanenon and it was established that the energy travelled in two nodes with different velocities.It was found by analysis that as well as the Rayleigh surface wave on the edge, a seoond node travelling at about the shear velocity was excited and the calculated results gave reasonable agreement with the experiments.

Performance comparison of SSMF and ultra wave fibers for ultra-long-haul 40-Gb/s WDM transmission

We experimentally compare the performance of standard single-mode fiber (SSMF) and UltraWave fiber (UWF) for ultra-long-haul (ULH) 40-Gb/s wavelength- division- multiplexing transmissions. We used the carrier-suppressed return-to-zero amplitude-shift-keying (CSRZ-ASK) and the carrier-suppressed return-to-zero differential-phase-shift-keying (CSRZ-DPSK) formats, which are particularly well-adapted to 40-Gb/s pulse-overlapped propagation. We demonstrate that transmission distance well beyond 2000 km can be reached on UWF with both the CSRZ-ASK and CSRZ-DPSK formats, or on SSMF with the CSRZ-DPSK format only, thus indicating that SSMF-based infrastructure of incumbent carriers can be upgraded at 40-Gb/s channel rates to ULH distances. © 2007 IEEE.

Accurate modelling of pulse transformation by adjustable-in-time medium parameters

A possibility of a strong change of an electromagnetic signal by a short sequence of time cycles of pulses that modulate the medium parameters is shown. The backward wave is demonstrated to be an inevitable result of the medium time change. Dependence of the relation between backward and forward waves on the parameters of the medium modulation is investigated. The finite statistical complexity of the electromagnetic signal transformed by a finite sequence of modulating cycles is calculated. Increase of the complexity with the number of cycles is shown.

Travelling-wave model of semiconductor optical amplifier based non-linear loop mirror

A travelling-wave model of a semiconductor optical amplifier based non-linear loop mirror is developed to investigate the importance of travelling-wave effects and gain/phase dynamics in predicting device behaviour. A constant effective carrier recovery lifetime approximation is found to be reasonably accurate (±10%) within a wide range of control pulse energies. Based on this approximation, a heuristic model is developed for maximum computational efficiency. The models are applied to a particular configuration involving feedback.

Generation of optical frequency combs in fibres:an optical pulse analysis

The innovation of optical frequency combs (OFCs) generated in passive mode-locked lasers has provided astronomy with unprecedented accuracy for wavelength calibration in high-resolution spectroscopy in research areas such as the discovery of exoplanets or the measurement of fundamental constants. The unique properties of OCFs, namely a highly dense spectrum of uniformly spaced emission lines of nearly equal intensity over the nominal wavelength range, is not only beneficial for high-resolution spectroscopy. Also in the low- to medium-resolution domain, the OFCs hold the promise to revolutionise the calibration techniques. Here, we present a novel method for generation of OFCs. As opposed to the mode-locked laser-based approach that can be complex, costly, and difficult to stabilise, we propose an all optical fibre-based system that is simple, compact, stable, and low-cost. Our system consists of three optical fibres where the first one is a conventional single-mode fibre, the second one is an erbium-doped fibre and the third one is a highly nonlinear low-dispersion fibre. The system is pumped by two equally intense continuous-wave (CW) lasers. To be able to control the quality and the bandwidth of the OFCs, it is crucial to understand how optical solitons arise out of the initial modulated CW field in the first fibre. Here, we numerically investigate the pulse evolution in the first fibre using the technique of the solitons radiation beat analysis. Having applied this technique, we realised that formation of higherorder solitons is supported in the low-energy region, whereas, in the high-energy region, Kuznetsov-Ma solitons appear.

New nonlinear regimes of pulse generation in mode- locked fiber lasers

Mode-locked fiber lasers provide convenient and reproducible experimental settings for the study of a variety of nonlinear dynamical processes. The complex interplay among the effects of gain/loss, dispersion and nonlinearity in a fiber cavity can be used to shape the pulses and manipulate and control the light dynamics and, hence, lead to different mode-locking regimes. Major steps forward in pulse energy and peak power performance of passively mode-locked fiber lasers have been made with the recent discovery of new nonlinear regimes of pulse generation, namely, dissipative solitons in all-normal-dispersion cavities and parabolic self-similar pulses (similaritons) in passive and active fibers. Despite substantial research in this field, qualitatively new phenomena are still being discovered. In this talk, we review recent progress in the research on nonlinear mechanisms of pulse generation in passively mode-locked fiber lasers. These include similariton mode-locking, a mode-locking regime featuring pulses with a triangular distribution of the intensity, and spectral compression arising from nonlinear pulse propagation. We also report on the possibility of achieving various regimes of advanced temporal waveform generation in a mode-locked fiber laser by inclusion of a spectral filter into the laser cavity.