Identification of visual field progression

The study developed statistical techniques to evaluate visual field progression for use with the Humphrey Field Analyzer (HFA). The long-term fluctuation (LF) was evaluated in stable glaucoma. The magnitude of both LF components showed little relationship with MD, CPSD and SF. An algorithm was proposed for determining the clinical necessity for a confirmatory follow-up examination. The between-examination variability was determined for the HFA Standard and FASTPAC algorithms in glaucoma. FASTPAC exhibited greater between-examination variability than the Standard algorithm across the range of sensitivities and with increasing eccentricity. The difference in variability between the algorithms had minimal clinical significance. The effect of repositioning the baseline in the Glaucoma Change Probability Analysis (GCPA) was evaluated. The global baseline of the GCPA limited the detection of progressive change at a single stimulus location. A new technique, pointwise univariate linear regressions (ULR), of absolute sensitivity and, of pattern deviation, against time to follow-up was developed. In each case, pointwise ULR was more sensitive to localised progressive changes in sensitivity than ULR of MD, alone. Small changes in sensitivity were more readily determined by the pointwise ULR than by the GCPA. A comparison between the outcome of pointwise ULR for all fields and for the last six fields manifested linear and curvilinear declines in the absolute sensitivity and the pattern deviation. A method for delineating progressive loss in glaucoma, based upon the error in the forecasted sensitivity of a multivariate model, was developed. Multivariate forecasting exhibited little agreement with GCPA in glaucoma but showed promise for monitoring visual field progression in OHT patients. The recovery of sensitivity in optic neuritis over time was modelled with a Cumulative Gaussian function. The rate and level of recovery was greater in the peripheral than the central field. Probability models to forecast the field of recovery were proposed.

An investigation of reading ability and visual function with eccentric visual field

This study investigated the detrimental effect of central field loss (CFL) on reading ability and general visual function. The aim was to improve the understanding of reading with eccentric retina in order that reading performances of individuals with CFL may be maximised. To improve visual ability of individuals with CFL, it is important to be able to accurately measure the outcome of any intervention. Various methods for determining visual function were therefore compared with perceived visual performance (as measured with a quality of life questionnaire) before and after surgical removal of choroidal new vessels (CNV) in macular disease patients. The results highlight the importance of low contrast measures (low contrast visual acuity and contrast sensitivity) when investigating perceived reading performance. Reading speed was found to be important for reflecting changes in general visual quality of life. Potential causes for reduced peripheral reading ability were investigated using both normally sighted and CFL subjects. For normally sighted subjects reading eccentrically with rapid serial visual presentation (RSVP) text, the inferior visual field was a better position (in terms of reading speed) for the presentation of the text. The size of the visual span was found to reduce with increasing eccentricity of fixation, providing a potential reason for reduced peripheral reading performances. The investigation of the ability to use context when reading with peripheral retina resulted in conflicting results. Studies in this thesis found both a reduction and no reduction in the ability of the peripheral retina to utilise context compared to the fovea. Individuals with long-term CFL showed no improvement in peripheral reading ability over that found for normally sighted subjects reading at the same eccentricity.

Effects of pixel noise and stimulus structure on visual detection performance

This thesis consisted of two major parts, one determining the masking characteristics of pixel noise and the other investigating the properties of the detection filter employed by the visual system. The theoretical cut-off frequency of white pixel noise can be defined from the size of the noise pixel. The empirical cut-off frequency, i.e. the largest size of noise pixels that mimics the effect of white noise in detection, was determined by measuring contrast energy thresholds for grating stimuli in the presence of spatial noise consisting of noise pixels of various sizes and shapes. The critical i.e. minimum number of noise pixels per grating cycle needed to mimic the effect of white noise in detection was found to decrease with the bandwidth of the stimulus. The shape of the noise pixels did not have any effect on the whiteness of pixel noise as long as there was at least the minimum number of noise pixels in all spatial dimensions. Furthermore, the masking power of white pixel noise is best described when the spectral density is calculated by taking into account all the dimensions of noise pixels, i.e. width, height, and duration, even when there is random luminance only in one of these dimensions. The properties of the detection mechanism employed by the visual system were studied by measuring contrast energy thresholds for complex spatial patterns as a function of area in the presence of white pixel noise. Human detection efficiency was obtained by comparing human performance with an ideal detector. The stimuli consisted of band-pass filtered symbols, uniform and patched gratings, and point stimuli with randomised phase spectra. In agreement with the existing literature, the detection performance was found to decline with the increasing amount of detail and contour in the stimulus. A measure of image complexity was developed and successfully applied to the data. The accuracy of the detection mechanism seems to depend on the spatial structure of the stimulus and the spatial spread of contrast energy.

The chromatic visual evoked response as an indication of visual development

In an endeavour to provide further insight into the maturation of the cortical visual system in human infants, chromatic transient pattern reversal visual evoked potentials to red/green stimuli, were studied in a group of normal full term infants between the ages of 1 and 14 weeks post term in both cross sectional and longitudinal studies. In order to produce stimuli in which luminance cues had been eliminated with an aim to eliciting a chromatic response, preliminary studies of isoluminance determination in adults and infants were undertaken using behavioural and electrophysiological techniques. The results showed close similarity between the isoluminant ratio for adults and infants and all values were close to photometric isoluminance. Pattern reversal VEPs were recorded to stimuli of a range of red/green luminance ratios and an achromatic checkerboard. No transient VEP could be elicited with an isoluminant chromatic pattern reversal stimulus from any infant less than 7 weeks post term and similarly, all infants more than 7 weeks post term showed clear chromatic VEPs. The chromatic response first appeared at that age as a major positive component (P1) of long latency. This was delayed and reduced in comparison to the achromatic response. As the infant grew older, the latency of the P1 component decreased with the appearance of N1 and N by the 10th week post term. This finding was consistent throughout all infants assessed. In a behavioural study, no infant less than 7 weeks post term demonstrated clear discrimination of the chromatic stimulus, while those infants older than 7 weeks could do so. These findings are reviewed with respect to current neural models of visual development.

The development of the visual system in pre-term infants as assessed by electrophysiological techniques

In an endeavour to provide further insight into the maturation of the human visual system, the contiguous development of the pattern reversal VEP, flash VEP and flash ERG was studied in a group of neurologically normal pre-term infants, born between 28 and 35 weeks gestation. Maturational changes were observed in all the evoked electrophysiological responses recorded, these were mainly characterised by an increase in the complexity of the waveform and a shortening in the latency of the response. Initially the ERG was seen to consist of a broad b-wave only, with the a-wave emerging at an average age of 40 weeks PMA. The a-wave showed only a slight reduction in latency and a modest increase in amplitude as the infant grows older, whereas the changes seen in the ERG b-wave were much more dramatic. Pattern reversal VEPs were successfully recorded for the first time during the pre-term period. Flash VEPs were also recorded for comparison. The neonatal pattern reversal VEP consistently showed a major positive component (P1) of long latency. As the infant grew older, the latency of the P1 component decreased and was found to be negatively correlated with PMA at recording. The appearance of the N1 and N2 components became more frequent as the infant matured. The majority of infants were found to be myopic at birth and refractive error was correlated with PMA, with emmetropisation occurring at about 45 weeks PMA. The pattern reversal VEP in response to 2o checks was apparently unaffected by refractive error.

Effect of disability glare on visual performance

The object of the study was to investigate, establish and quantify the relationship between contrast sensitivity, intraocular light scatter and glare. The aim was to establish the effects on vision, in an effort to provide a more comprehensive understanding of the visual world of subjects prone to increased light scatter in the eye. Disability glare refers to the reduction in visual performance produced by a glare source. The reduction in visual performance can be explained by intraocular scattered light producing a veiling luminance which is superimposed upon the retinal image. This veiling luminance lowers contrast thus sensitivity to the stimulus declines. The effect of glare of luminance and colour contrast sensitivity for young and elderly subjects was examined. For both age groups, disability glare was greatest for the red-green stimulus and least for the blue-yellow. The precise effect of a glare source on colour discrimination depends upon the interaction between the chromaticity of the glare source and that of the stimulus. The effect of a long wavelength pass (red) and a short wavelength pass filter (blue) on disability glare was examined. Disability glare was not significantly different with the red and blue filters, even in the presence of wavelength dependent scatter. An equation was derived which allowed an intrinsic Light Scatter Factor (LSF) to be determined for any given glare angle (Paulsson and Sjöstrand, 1980). Corrections to the formula to account for factors such as pupil size changes are unnecessary. The results confirm the suitability of measuring the LSF using contrast threshold with and without glare, provided that appropriate methods are used. Using this formula an investigation into the amount of wavelength dependent scatter indicated that wavelength dependent scatter in normal young, elderly or cataractous eyes is of little or no significance. Finally, it seemed desirable to investigate the effect ultraviolet (UV) radiation has on intraocular light scatter and subsequently visual performance. Overall the results indicated that the presence or absence of UV radiation has relatively little effect on visual function for the young, elderly or cataract patient.

Mode control in multimode optical fibre and its applications

This thesis describes an investigation into methods for controlling the mode distribution in multimode optical fibres. The major contributions presented in this thesis are summarised below. Emerging standards for Gigabit Ethernet transmission over multimode optical fibre have led to a resurgence of interest in the precise control, and specification, of modal launch conditions. In particular, commercial LED and OTDR test equipment does not, in general, comply with these standards. There is therefore a need for mode control devices, which can ensure compliance with the standards. A novel device consisting of a point-load mode-scrambler in tandem with a mode-filter is described in this thesis. The device, which has been patented, may be tuned to achieve a wide range of mode distributions and has been implemented in a ruggedised package for field use. Various other techniques for mode control have been described in this work, including the use of Long Period Gratings and air-gap mode-filters. Some of the methods have been applied to other applications, such as speckle suppression and in sensor technology. A novel, self-referencing, sensor comprising two modal groups in the Mode Power Distribution has been designed and tested. The feasibility of a two-channel Mode Group Diversity Multiplexed system has been demonstrated over 985m. A test apparatus for measuring mode distribution has been designed and constructed. The apparatus consists of a purpose-built video microscope, and comprehensive control and analysis software written in Visual Basic. The system may be fitted with a Silicon camera or an InGaAs camera, for measurement in the 850nm and 130nm transmission windows respectively. A limitation of the measurement method, when applied to well-filled fibres, has been identified and an improvement to the method has been proposed, based on modelled Laguerre Gauss field solutions.

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.

Comparison between femtosecond laser and fusion-arc inscribed long period gratings in photonic crystal fibre

The use of high intensity femtosecond laser sources for inscribing fibre gratings has attained significant interest. The principal advantage of high-energy pulses is their ability for grating inscription in any material type without preprocessing or special core doping. In the field of fibre optical sensing LPGs written in photonic crystal fibre have a distinct advantage of low temperature sensitivity over gratings written in conventional fibre and thus minimal temperature cross-sensitivity. Previous studies have indicated that LPGs written by a point-by-point inscription scheme using a low repetition femtosecond laser exhibit post-fabrication evolution leading to temporal instabilities at room temperatures with respect to spectral location, strength and birefringence of the attenuation bands. These spectral instabilities of LPGs are studied in photonic crystal fibres (endlessly single mode microstructure fibre) to moderately high temperatures 100°C to 200°C and their performance compared to fusion-arc fabricated LPG. Initial results suggest that the fusion-arc fabricated LPG demonstrate less spectral instability for a given constant and moderate temperature, and are similar to the results obtained when inscribed in a standard single mode fibre.

The SECURE study:long-term safety of Ranibizumab 0.5 mg in neovascular age-related macular degeneration

Objective - To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Design - Twenty-four–month, open-label, multicenter, phase IV extension study. Participants - Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Methods - Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Main Outcome Measures - Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Results - Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. Conclusions - The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

Modulational instabilities in fibres with periodic dispersion

We analytically and numerically analyze the occurrence of modulational instability in fibers with periodic changes in the group-velocity dispersion. For small variations, a set of resonances occurs in the gain spectrum. However, large dispersion variations eliminate these resonances and restrict the bandwidth of the fundamental gain spectrum. This research has been motivated by the adoption of dispersion management techniques in long-haul optical communications.

Bend and index insensitive long period grating in progressive three layered optical fibre

A long period fibre grating written in progressive three layered optical fibre was examined. The bending sensitivity of the optical fibre was measured. It was found that the fibre shows an attenuation band that has a very low bending sensitivity compared to normal step-index fibres.

Measured sensitivity of arc-induced long-period grating sensors in photonic crystal fibre

Reported are experimental results from investigations of the sensing properties of long-period gratings (LPGs) recorded in two different geometries of photonic crystal fibre (PCF): a large-mode area PCF and an endlessly single mode PCF. The LPGs have been characterised for their sensitivity to temperature, bending, surrounding index and strain. The LPGs in both fibres have been found to have negligible temperature sensitivity whilst exhibiting useful strain sensitivities. Strong directional bend sensitivity is shown by one PCF whilst the other shows good non-directional bend sensitivity. The fibres exhibit differing sensitivities to surrounding refractive index. © 2005 Elsevier B.V. All rights reserved.

Anticipatory control of long-range phase synchronization

Everyday human behaviour relies on our ability to predict outcomes on the basis of moment by moment information. Long-range neural phase synchronization has been hypothesized as a mechanism by which ‘predictions’ can exert an effect on the processing of incoming sensory events. Using magnetoencephalography (MEG) we have studied the relationship between the modulation of phase synchronization in a cerebral network of areas involved in visual target processing and the predictability of target occurrence. Our results reveal a striking increase in the modulation of phase synchronization associated with an increased probability of target occurrence. These observations are consistent with the hypothesis that long-range phase synchronization plays a critical functional role in humans' ability to effectively employ predictive heuristics.

Cortical dynamics and synchronization related to multiple target consolidation under rapid-serial-visual-presentation conditions

The present report reviews behavioural, electroencephalographic, and especially magnetoencephalographic findings on the cortical mechanisms underlying attentional processes that separate targets from distractors and that ensure durable target representations for goal-directed action. A common way of investigation is to observe the system’s overt and covert behaviour when capacity limitations are reached. Here we focus on the aspect of temporally enhanced processing load, namely on performance deficits occurring under rapid-serial-visual-presentation (RSVP) conditions. The most prominent of these deficits is the so-called “attentional blink” (AB) effect. We first report MEG findings with respect to the time course of activation that shows modulations around 300 ms after target onset which reflect demands and success of target consolidation. Then, findings regarding long-range inter-area phase synchronization are reported that are hypothesized to mediate communication within the attentional network. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioural performance. Furthermore, enhanced vigilance of the system elicits systematically increased synchronization indices. A hypothetical framework is sketched out that aims at explaining limitations in multiple target consolidation under RSVP conditions.