Localized retinal nerve fiber layer defects and arterial hypertension:insights into pathophysiology and perhaps an eye for detail?

Retinal microcirculatory changes are useful markers in patients suffering from hypertension and other cardiovascular disorders. Conversely, localized retinal nerve fiber layer defects (RNFLDs) are less frequently explored in association with hypertension.

Structure and function in primary open angle glaucoma

The study utilised a Normal group, an Ocular Hypertensive (OHT) group and a Primary Open Angle Glaucoma (POAG) group to investigate two aspects. Firstly, the within- and between-visit variability for stereometric measurements of the optic nerve head (ONH) using the Heidelberg Retina Tomograph (HRT); retinal nerve fibre layer (RNFL) thickness using the HRT and using optical coherence tomography with the Optical Coherence Tomography Scanner (OCT); the visual field using white-on-white (W-W), short-wavelength (SWAP) and Frequency Doubling perimetry (FDT); and retinal haemodynamics using the Heidelberg Retinal Flowmeter (HRF). Secondly, the association demonstrated between some of the derived variables. The within- and between-visit variability for stereometric measurements of the entire ONH and the between-visit variability for sectoral measurements were similar for Normals and OHTs but greater for POAGs. The within-visit variability of the visual field pointwise parameters for SWAP were greater than for W-W and FDT particularly with increase in eccentricity and for the OHT group. The between-visit variability increased with increase in defect depth for the POAG group, across all types of perimetry. The MS was greater, the MD and PSD smaller and the examination duration shorter in FDT compared to W-W and SWAP across all groups. The within-visit variability was less than the between-visit variability for the OCT circumferential and sector RNFL thickness using the 1.5R, 2.0R and the fixed 1.73mm circular scan radii, across the three groups. The variability increased with decrease in the RNFL thickness, and was least for the 2.0R scan radius.

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.

Regression analysis of ranked segment parameters for optic nerve head classification:a pilot study

Purpose: To determine whether curve-fitting analysis of the ranked segment distributions of topographic optic nerve head (ONH) parameters, derived using the Heidelberg Retina Tomograph (HRT), provide a more effective statistical descriptor to differentiate the normal from the glaucomatous ONH. Methods: The sample comprised of 22 normal control subjects (mean age 66.9 years; S.D. 7.8) and 22 glaucoma patients (mean age 72.1 years; S.D. 6.9) confirmed by reproducible visual field defects on the Humphrey Field Analyser. Three 10°-images of the ONH were obtained using the HRT. The mean topography image was determined and the HRT software was used to calculate the rim volume, rim area to disc area ratio, normalised rim area to disc area ratio and retinal nerve fibre cross-sectional area for each patient at 10°-sectoral intervals. The values were ranked in descending order, and each ranked-segment curve of ordered values was fitted using the least squares method. Results: There was no difference in disc area between the groups. The group mean cup-disc area ratio was significantly lower in the normal group (0.204 ± 0.16) compared with the glaucoma group (0.533 ± 0.083) (p < 0.001). The visual field indices, mean deviation and corrected pattern S.D., were significantly greater (p < 0.001) in the glaucoma group (-9.09 dB ± 3.3 and 7.91 ± 3.4, respectively) compared with the normal group (-0.15 dB ± 0.9 and 0.95 dB ± 0.8, respectively). Univariate linear regression provided the best overall fit to the ranked segment data. The equation parameters of the regression line manually applied to the normalised rim area-disc area and the rim area-disc area ratio data, correctly classified 100% of normal subjects and glaucoma patients. In this study sample, the regression analysis of ranked segment parameters method was more effective than conventional ranked segment analysis, in which glaucoma patients were misclassified in approximately 50% of cases. Further investigation in larger samples will enable the calculation of confidence intervals for normality. These reference standards will then need to be investigated for an independent sample to fully validate the technique. Conclusions: Using a curve-fitting approach to fit ranked segment curves retains information relating to the topographic nature of neural loss. Such methodology appears to overcome some of the deficiencies of conventional ranked segment analysis, and subject to validation in larger scale studies, may potentially be of clinical utility for detecting and monitoring glaucomatous damage. © 2007 The College of Optometrists.

Stochastic beamforming for cochlear implant coding

Cochlear implants are prosthetic devices used to provide hearing to people who would otherwise be profoundly deaf. The deliberate addition of noise to the electrode signals could increase the amount of information transmitted, but standard cochlear implants do not replicate the noise characteristic of normal hearing because if noise is added in an uncontrolled manner with a limited number of electrodes then it will almost certainly lead to worse performance. Only if partially independent stochastic activity can be achieved in each nerve fibre can mechanisms like suprathreshold stochastic resonance be effective. We are investigating the use of stochastic beamforming to achieve greater independence. The strategy involves presenting each electrode with a linear combination of independent Gaussian noise sources. Because the cochlea is filled with conductive salt solutions, the noise currents from the electrodes interact and the effective stimulus for each nerve fibre will therefore be a different weighted sum of the noise sources. To some extent therefore, the effective stimulus for a nerve fibre will be independent of the effective stimulus of neighbouring fibres. For a particular patient, the electrode position and the amount of current spread are fixed. The objective is therefore to find the linear combination of noise sources that leads to the greatest independence between nerve discharges. In this theoretical study we show that it is possible to get one independent point of excitation (one null) for each electrode and that stochastic beamforming can greatly decrease the correlation between the noise exciting different regions of the cochlea. © 2007 Copyright SPIE - The International Society for Optical Engineering.

Regional variability in visual field sensitivity during hypercapnia

PURPOSE: Previous investigations have demonstrated a relative vascular autoregulatory inefficiency of the inferior compared to the superior retina in healthy subjects breathing increased CO2. The purpose of this study was to determine whether the superior and inferior visual field sensitivities of healthy eyes are similarly affected during mild hypercapnia. DESIGN: Experimental study. METHODS: Visual field analysis (Humphrey Field Analyser; SITA standard 24-2 program) was carried out on one randomly selected eye of 22 subjects (mean age, 27.7 ± 5 years) during normal room air breathing and isoxic hypercapnia. The Student paired t-tests were used to compare the visual field indices mean deviation (MD) and pattern standard deviation (PSD) for each breathing condition. A secondary, sectoral analysis of mean pointwise sensitivity was performed for each condition. In each case a P value of <.01 was considered statistically significant (Bonferroni corrected). RESULTS: Visual field MD was -0.23 ± 0.95dB during room air breathing and -0.49 ± 1.04dB during hypercapnia (P = .034). Sectoral pointwise mean sensitivity deteriorated by 0.46dB (P = .006) in the upper visual hemifield during hypercapnia, whereas no significant difference was observed for the lower hemifield (P = .331). CONCLUSIONS: The upper visual hemifield exhibited a significantly greater degree of deterioration in pointwise visual field mean sensitivity compared to the lower hemifield during hypercapnic conditions. This suggests that the upper visual hemifield and hence inferior retina is more susceptible to insult during hypercapnia than the superior retina in healthy individuals. A regional susceptibility of inferior retinal function to altered vascular or metabolic effects may account for the earlier and more frequent inferior nerve fibre damage associated with glaucomatous optic neuropathy. © 2003 by Elsevier Science Inc. All rights reserved.

The benefit of combining standard automated perimetry and multifocal visual evoked potential hemifield intersector analysis in suspecious glaucomatous visual field defects

Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard SAP visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. The purpose of this study is to examine the benefit of adding mfVEP hemifield Intersector analysis protocol to the standard HFA test when there is suspicious glaucomatous visual field loss. 3 groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey visual field HFA test 24-2, optical coherence tomography of the optic nerve head, and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the Hemifield Sector Analysis HSA protocol. The retinal nerve fibre (RNFL) thickness was recorded to identify subjects with suspicious RNFL loss. The hemifield Intersector analysis of mfVEP results showed that signal to noise ratio (SNR) difference between superior and inferior hemifields was statistically significant between the 3 groups (ANOVA p<0.001 with a 95% CI). The difference between superior and inferior hemispheres in all subjects were all statistically significant in the glaucoma patient group 11/11 sectors (t-test p<0.001), partially significant 5/11 in glaucoma suspect group (t-test p<0.01) and no statistical difference between most sectors in normal group (only 1/11 was significant) (t-test p<0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86% respectively, while for glaucoma suspect were 89% and 79%. The use of SAP and mfVEP results in subjects with suspicious glaucomatous visual field defects, identified by low RNFL thickness, is beneficial in confirming early visual field defects. The new HSA protocol used in the mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patient. Using this protocol in addition to SAP analysis can provide information about focal visual field differences across the horizontal midline, and confirm suspicious field defects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss. The Intersector analysis protocol can detect early field changes not detected by standard HFA test.

Optical fibre sensors with applications in gas and biological sensing

This thesis describes the study of various grating based optical fibre sensors for applications in refractive index sensing. The sensitivity of these sensors has been studied and in some cases enhanced using novel techniques. The major areas of development are as follows. The sensitivity of long period gratings (LPGs) to surrounding medium refractive index (SRI) for various periods was investigated. The most sensitive period of LPG was found to be around 160 µm and this was due to the core mode coupling to a single cladding mode but phase matching at two wavelength locations, creating two attenuation peaks, close to the waveguide dispersion turning point. Large angle tilted fibre gratings (TFGs) have similar behaviour to LPGs, in that they couple to the co-propagating cladding modes. The tilted structure of the index modulation within the core of the fibre gives rise to a polarisation dependency, differing the large angle TFG from a LPG. Since the large angle TFG couple to the cladding mode they are SRI sensitive, the sensitivity to SRI can be further increased through cladding etching using HF acid. The thinning of the cladding layer caused a reordering of the cladding modes and shifted to more SRI sensitive cladding modes as the investigation discovered. In a SRI range of 1.36 to 1.40 a sensitivity of 506.9 nm/URI was achieved for the etched large angle TFG, which is greater than the dual resonance LPG. UV inscribed LPGs were coated with sol-gel materials with high RIs. The high RI of the coating caused an increase in cladding mode effective index which in turn caused an increase in the LPG sensitivity to SRI. LPGs of various periods of LPG were coated with sol-gel TiO2 and the optimal thickness was found to vary for each period. By coating of the already highly SRI sensitive 160µm period LPG (which is a dual resonance) with a sol-gel TiO2, the SRI sensitivity was further increased with a peak value of 1458 nm/URI, which was an almost 3 fold increase compared to the uncoated LPG. LPGs were also inscribed using a femtosecond laser which produced a highly focused index change which was no uniform throughout the core of the optical fibre. The inscription technique gave rise to a large polarisation sensitivity and the ability to couple to multiple azimuthal cladding mode sets, not seen with uniform UV inscribed gratings. Through coupling of the core mode to multiple sets of cladding modes, attenuation peaks with opposite wavelength shifts for increasing SRI was observed. Through combining this opposite wavelength shifts, a SRI sensitivity was achieved greater than any single observed attenuations peak. The maximum SRI achieved was 1680 nm/URI for a femtosecond inscribed LPG of period 400 µm. Three different types of surface plasmon resonance (SPR) sensors with a multilayer metal top coating were investigated in D shape optical fibre. The sensors could be separated into two types, utilized a pre UV inscribed tilted Bragg grating and the other employed a post UV exposure to generate surface relief grating structure. This surface perturbation aided the out coupling of light from the core but also changed the sensing mechanism from SPR to localised surface plasmon resonance (LSPR). This greatly increased the SRI sensitivity, compared to the SPR sensors; with the gold coated top layer surface relief sensor producing the largest SRI sensitivity of 2111.5nm/URI was achieved. While, the platinum and silver coated top layer surface relief sensors also gave high SRI sensitivities but also the ability to produce resonances in air (not previously seen with the SPR sensors). These properties were employed in two applications. The silver and platinum surface relief devices were used as gas sensors and were shown to be capable of detecting the minute RI change of different gases. The calculated maximum sensitivities produced were 1882.1dB/URI and 1493.5nm/URI for silver and platinum, respectively. Using a DFB laser and power meter a cheap alternative approach was investigated which showed the ability of the sensors to distinguish between different gases and flow rates of those gases. The gold surface relief sensor was coated in a with a bio compound called an aptamer and it was able to detect various concentrations of a biological compound called Thrombin, ranging from 1mM to as low as 10fM. A solution of 2M NaCl was found to give the best stripping results for Thrombin from the aptamer and showed the reusability of the sensor. The association and disassociation constants were calculated to be 1.0638×106Ms-1 and 0.2482s-1, respectively, showing the high affinity of the Aptamer to thrombin. This supports existing working stating that aptamers could be alternative to enzymes for chemical detection and also helps to explain the low detection limit of the gold surface relief sensor.

Fibre gratings in novel optical fibres for applications in sensing

This thesis presents the fabrication of fibre gratings in novel optical fibres for sensing applications. Long period gratings have been inscribed into photonic crystal fibre using the electric-arc technique. The resulting sensing characteristics were found to depend on the air-hole geometry of the particular fibre. This provides the potential of designing a fibre to have enhanced sensitivity to a particular measure and whilst removing unwanted cross sensitivities. Fibre Bragg gratings have been fabricated in a variety of polymer optical fibres, including microstructured polymer optical fibre, using a continuous wave helium cadmium laser. The thermal response of the gratings have been characterised and found to have enhanced sensitivity compared to fibre Bragg gratings in silica optical fibre. The increased sensitivity has been harnessed to achieve a grating based device in single mode step index polymer optical fibre by fabricating an electrically tunable fibre Bragg grating. This was accomplished by coating the grating region in a thin layer of copper, which upon application of a direct current, causes a temperature induced Bragg wavelength shift.

Development of an electrically tuneable Bragg grating filter in polymer optical fibre operating at 1.55 µm

We present a thorough study on the development of a polymer optical fibre-based tuneable filter utilizing an intra-core Bragg grating that is electrically tuneable, operating at 1.55 µm. The Bragg grating is made tuneable using a thin-film resistive heater deposited on the surface of the fibre. The polymer fibre was coated via the photochemical deposition of a Pd/Cu metallic layer with the procedure induced by VUV radiation at room temperature. The resulting device, when wavelength tuned via Joule heating, underwent a wavelength shift of 2 nm for a moderate input power of 160 mW, a wavelength to input power coefficient of -13.4 pm mW-1 and time constant of 1.7 s-1. A basic theoretical study verified that for this fibre type one can treat the device as a one-dimensional system. The model was extended to include the effect of input electrical power changes on the refractive index of the fibre and subsequently to changes in the Bragg wavelength of the grating, showing excellent agreement with the experimental measurements.

Water detection in jet fuel using a polymer optical fibre Bragg grating

Water is a common impurity of jet fuel, and can exist in three forms: dissolved in the fuel, as a suspension and as a distinct layer at the bottom of the fuel tank. Water cannot practically be eliminated from fuel but must be kept to a minimum as large quantities can cause engine problems, particularly when frozen, and the interface between water and fuel acts as a breeding ground for biological contaminants. The quantities of dissolved or suspended water are quite small, ranging from about 10 ppm to 150 ppm. This makes the measurement task difficult and there is currently a lack of a convenient, electrically passive system for water-in-fuel monitoring; instead the airlines rely on colorimetric spot tests or simply draining liquid from the bottom of fuel tanks. For all these reason, people have explored different ways to detect water in fuel, however all these approaches have problems, e.g. they may not be electrically passive or they may be sensitive to the refractive index of the fuel. In this paper, we present a simple, direct and sensitive approach involving the use of a polymer optical fibre Bragg grating to detect water in fuel. The principle is that poly(methyl methacrylate) (PMMA) can absorb moisture from its surroundings (up to 2% at 23 °C), leading to both a swelling of the material and an increase in refractive index with a consequent increase in the Bragg wavelength of a grating inscribed in the material.

Development of an electrically tuneable Bragg grating filter in polymer optical fibre operating at 1.55 νm

We present a thorough study on the development of a polymer optical fibre-based tuneable filter utilizing an intra-core Bragg grating that is electrically tuneable, operating at 1.55 νm. The Bragg grating is made tuneable using a thin-film resistive heater deposited on the surface of the fibre. The polymer fibre was coated via the photochemical deposition of a Pd/Cu metallic layer with the procedure induced by VUV radiation at room temperature. The resulting device, when wavelength tuned via Joule heating, underwent a wavelength shift of 2 nm for a moderate input power of 160 mW, a wavelength to input power coefficient of -13.4 pm mW-1 and time constant of 1.7 s-1. A basic theoretical study verified that for this fibre type one can treat the device as a one-dimensional system. The model was extended to include the effect of input electrical power changes on the refractive index of the fibre and subsequently to changes in the Bragg wavelength of the grating, showing excellent agreement with the experimental measurements. © 2007 IOP Publishing Ltd.

Water detection in jet fuel using a polymer optical fibre Bragg grating

Water is a common impurity of jet fuel, and can exist in three forms: dissolved in the fuel, as a suspension and as a distinct layer at the bottom of the fuel tank. Water cannot practically be eliminated from fuel but must be kept to a minimum as large quantities can cause engine problems, particularly when frozen, and the interface between water and fuel acts as a breeding ground for biological contaminants. The quantities of dissolved or suspended water are quite small, ranging from about 10 ppm to 150 ppm. This makes the measurement task difficult and there is currently a lack of a convenient, electrically passive system for water-in-fuel monitoring; instead the airlines rely on colorimetric spot tests or simply draining liquid from the bottom of fuel tanks. For all these reason, people have explored different ways to detect water in fuel, however all these approaches have problems, e.g. they may not be electrically passive or they may be sensitive to the refractive index of the fuel. In this paper, we present a simple, direct and sensitive approach involving the use of a polymer optical fibre Bragg grating to detect water in fuel. The principle is that poly(methyl methacrylate) (PMMA) can absorb moisture from its surroundings (up to 2% at 23 °C), leading to both a swelling of the material and an increase in refractive index with a consequent increase in the Bragg wavelength of a grating inscribed in the material.

Monitoring of deployment process of shape memory polymers for morphing structures with embedded fibre Bragg grating sensors

This article demonstrates the use of embedded fibre Bragg gratings as vector bending sensor to monitor two-dimensional shape deformation of a shape memory polymer plate. The shape memory polymer plate was made by using thermal-responsive epoxy-based shape memory polymer materials, and the two fibre Bragg grating sensors were orthogonally embedded, one on the top and the other on the bottom layer of the plate, in order to measure the strain distribution in both longitudinal and transverse directions separately and also with temperature reference. When the shape memory polymer plate was bent at different angles, the Bragg wavelengths of the embedded fibre Bragg gratings showed a red-shift of 50 pm/°caused by the bent-induced tensile strain on the plate surface. The finite element method was used to analyse the stress distribution for the whole shape recovery process. The strain transfer rate between the shape memory polymer and optical fibre was also calculated from the finite element method and determined by experimental results, which was around 0.25. During the experiment, the embedded fibre Bragg gratings showed very high temperature sensitivity due to the high thermal expansion coefficient of the shape memory polymer, which was around 108.24 pm/°C below the glass transition temperature (Tg) and 47.29 pm/°C above Tg. Therefore, the orthogonal arrangement of the two fibre Bragg grating sensors could provide a temperature compensation function, as one of the fibre Bragg gratings only measures the temperature while the other is subjected to the directional deformation. © The Author(s) 2013.

UV inscribed long period gratings with femtosecond ablated axial fibre slots for polarization control

We present data on the development a new type of optical fibre polariser and the characterisation of its wavelength properties. The device is fashioned using a two step process. Firstly, a standard UV long period grating (LPG) with a period of 330μm is inscribed into hydrogenated SMF-28, followed by femtosecond laser ablation of a groove parallel to the fibre axis. The UV inscribed LPGs have inherently low birefringence. However, the removal of the cladding layer parallel to the location of the LPG within the fibre core (as a result the ablation) modifies the cladding modes that couple with the LPG. Furthermore, the groove breaks the fibre symmetry introducing a non-uniform stress profile across the fibre cross section leading to significant birefringence. We show that increasing the depth of the groove increases the birefringence, and this behaviour coupled with the ability to control the wavelength location of the LPGs attenuations peaks results in a polariser able to operate at almost any wavelength and birefringence. The maximum birefringence reported here as polarisation mode splitting was approximately 39±0.1nm with a polarisation loss of 10dB. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).