Assessing visual fields for driving in patients with paracentral scotomata

Background: The binocular Esterman visual field test (EVFT) is the current visual field test for driving in the UK. Merging of monocular field tests (Integrated Visual Field, IVF) has been proposed as an alternative for glaucoma patients. Aims: To examine the level of agreement between the EVFT and IVF for patients with binocular paracentral scotomata, caused by either ophthalmological or neurological conditions, and to compare outcomes with useful field of view (UFOV) performance, a test of visual attention thought to be important in driving. Methods: 60 patients with binocular paracentral scotomata but normal visual acuity (VA) were recruited prospectively. Subjects completed and were classified as “pass” or “fail” for the EVFT, IVF and UFOV. Results: Good agreement occurred between the EVFT and IVF in classifying subjects as “pass” or “fail” (kappa?=?0.84). Classifications disagreed for four subjects with paracentral scotomata of neurological origin (three “passed” IVF yet “failed” EVFT). Mean UFOV scores did not differ between those who “passed” and those who “failed” both visual field tests (p?=?0.11). Agreement between the visual field tests and UFOV was limited (EVFT kappa?=?0.22, IVF kappa 0.32). Conclusions: Although the IVF and EVFT agree well in classifying visual fields with regard to legal fitness to drive in the UK, the IVF “passes” some individuals currently classed as unfit to drive due to paracentral scotomata of non-glaucomatous origin. The suitability of the UFOV for assessing crash risk in those with visual field loss is questionable.

Characteristics of visual function in Asperger’s syndrome and the autism spectrum

Autism is a pervasive developmental disorder and Asperger’s syndrome is part of the spectrum of autism disorders. This thesis aims to: • Review and investigate current theories concerning visual function in individuals with Asperger’s syndrome and high functioning autism spectrum disorder and to translate the findings into clinical practice by developing a specific protocol for the eye examination of individuals of this population. • Investigate whether those with Asperger’s syndrome are more likely to suffer from Meares-Irlen syndrome and/or dyslexia. • Assess the integrity of the M-cell pathway in Asperger’s syndrome using perimetric tests available in optometric practice to investigate and also to describe the nature of any defects. • Evaluate eye movement strategies in Asperger’s whilst viewing both text and images. Also to evaluate the most appropriate methodology for investigating eye movements; namely optical digital eye tracking and electrophysiology methodologies. Findings of the investigations include • Eye examinations for individuals with Asperger’s syndrome should contain the same testing methods as for the general population, with special consideration for clear communication. • There is a depression of M-pathway visual field sensitivity in 57% (8/14) of people with Asperger’s syndrome, supporting previous evidence for an M-cell deficit in some individuals. • There is a raised prevalence of dyslexia in Asperger’s syndrome (26% of a sample of 31) but not necessarily of Meares-Irlen syndrome. • Gaze strategies are abnormal in Asperger’s syndrome, for both reading and viewing of images. With increased saccadic movement and decreased viewing of faces in comparison to background detail.

The effects of vigabatrin of the visual system

This thesis considers the visual electrophysiological effects of vigabatrin (an anti-epileptic drug, which acts by increasing the levels of the inhibitory neurotransmitter GABA on the retina of the eye compared to the concentric visual field defects which have been found associated with the drug. Flash and pattern ERG's, EOG's multifocal ERG's (VERIS), flash and pattern VEP's and visual fields were tested. Although VEP's have been shown not to be affected by vigabatrin, these were recorded to complete the testing. Initially, of the eight vigabatrin patients with known visual field defects, 7 showed abnormally delayed 30Hz flicker a-wave latencies, 5 abnormally delayed 30Hz b-wave latencies and 6 abnormally low 30Hz amplitudes. Also 7 showed an abnormally prolonged latency of oscillatory potential 1 (OP1). The two patients taking vigabatrin at the time of testing showed low EOG Arden index values. The VERIS results correlated well with the severity of the visual field defects. Following this finding, eleven healthy subjects received vigabatrin over a 10-day period. No changes were seen in the visual fields, however, the photopic ERG b-wave latency significantly increased (although not to abnormal values). A matched pairs study with eleven vigabatrin, patients and eleven epileptic patients, who had never taken vigabatrin supported the findings of abnormal 30Hz flicker b-wave and OP latencies associated with vigabatrin, again with the VERIS results correlating to the severity of the visual field defect. The abnormal 30Hz flicker and VERIS responses indicate involvement of the cone photoreceptors and the OP's show an effect on the amacrine cells. The ERG increase in the photopic b-wave latency also suggests involvement of the bipolar cells, however, this effect and the reversible effect on the Arden index after cessation of the drug may be unrelated to the visual field defect. To conclude this thesis, a field specific VEP stimulus was developed to assess the retinal function in the peripheral field of paediatric patients. It comprises of a dartboard stimulus with a central 0-5 degree black and white chequered stimulus, a blank 5-30 degree annulus and a 30-60 degree peripheral chequered stimulus. When optimised on four vigabatrin patients it was found that no peripheral response can be evoked with a field loss exceeding 30-35 degrees. Co-operation was found to be successful in children as young as four years old.

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Automated assessment of visual fields and their inter-relation to evoked potentials in visual disorders

The Octopus Automated Perimeter was validated in a comparative study and found to offer many advantages in the assessment of the visual field. The visual evoked potential was investigated in an extensive study using a variety of stimulus parameters to simulate hemianopia and central visual field defects. The scalp topography was recorded topographically and a technique to compute the source derivation of the scalp potential was developed. This enabled clarification of the expected scalp distribution to half field stimulation using different electrode montages. The visual evoked potential following full field stimulation was found to be asymmetrical around the midline with a bias over the left occiput particularly when the foveal polar projections of the occipital cortex were preferentially stimulated. The half field response reflected the distribution asymmetry. Masking of the central 3° resulted in a response which was approximately symmetrical around the midline but there was no evidence of the PNP-complex. A method for visual field quantification was developed based on the neural representation of visual space (Drasdo and Peaston 1982) in an attempt to relate visual field depravation with the resultant visual evoked potentials. There was no form of simple, diffuse summation between the scalp potential and the cortical generators. It was, however, possible to quantify the degree of scalp potential attenuation for M-scaled full field stimuli. The results obtained from patients exhibiting pre-chiasmal lesions suggested that the PNP-complex is not scotomatous in nature but confirmed that it is most likely to be related to specific diseases (Harding and Crews 1982). There was a strong correlation between the percentage information loss of the visual field and the diagnostic value of the visual evoked potential in patients exhibiting chiasmal lesions.

Investigation into visual defects attributed to Vigabatrin

Vigabatrin (VGB) is a transaminase inhibitor that elicits its anitepileptic effect by increasing GABA concentrations in the brain and retina. - Assess whether certain factors predispose patients to develop severe visual field loss. - Develop a sensitive algorithm for investigating the progression of visual field loss. - Determine the most sensitive clinical regimen for diagnosing VGB-attributed visual field loss. - Investigate whether the reports of central retinal sparing are accurate. The investigations have resulted in a number of significant findings: - The anatomical evidence in combination with the pattern of visual field loss suggests that the damage induced by VGB therapy occurs at retinal level, and is most likely a toxic effect. - The quantitative algorithm, designed within the course of this investigation, provided increased sensitivity in determining the severity of visual field loss. - Maximum VGB dose predisposes patients to develop severe visual field loss. - The SITA Standard algorithm was found to be as sensitive and significantly faster, in diagnosing visual field defects attributed to VGB, when compared to the Full Threshold algorithm. The Full Threshold was found to be the most repeatable between visits. - The normal SWAP 10-2 database provided an effective method of differentiating SWAP defects. - SWAP, FDT and the mfERG have increased sensitivity in detecting visual field loss attributed to VGB. The pattern of visual field loss from these investigations suggests that VGB produces a diffuse effect across the retina including subtle central abnormalities and more severe peripheral defects. - Abnormalities detected using the mfERG have suggested that VGB adversely affects the photoreceptors Müller, amacrine and ganglion cells in the retina. An urgent review of the manufacturers recommended maximum dose for VGB is required.

Visual symptoms in Parkinson's disease

Parkinson’s disease (PD) is a common disorder of middle-aged and elderly people in which degeneration of the extrapyramidal motor system causes significant movement problems. In some patients, however, there are additional disturbances in sensory systems including loss of the sense of smell and auditory and/or visual problems. This article is a general overview of the visual problems likely to be encountered in PD. Changes in vision in PD may result from alterations in visual acuity, contrast sensitivity, colour discrimination, pupil reactivity, eye movements, motion perception, visual field sensitivity and visual processing speeds. Slower visual processing speeds can also lead to a decline in visual perception especially for rapidly changing visual stimuli. In addition, there may be disturbances of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations. Some of the treatments used in PD may also have adverse ocular reactions. The pattern electroretinogram (PERG) is useful in evaluating retinal dopamine mechanisms and in monitoring dopamine therapies in PD. If visual problems are present, they can have an important effect on the quality of life of the patient, which can be improved by accurate diagnosis and where possible, correction of such defects.

Adults with dyslexia demonstrate large effects of crowding and detrimental effects of distractors in a visual tilt discrimination task

Previous research has shown that adults with dyslexia (AwD) are disproportionately impacted by close spacing of stimuli and increased numbers of distractors in a visual search task compared to controls [1]. Using an orientation discrimination task, the present study extended these findings to show that even in conditions where target search was not required: (i) AwD had detrimental effects of both crowding and increased numbers of distractors; (ii) AwD had more pronounced difficulty with distractor exclusion in the left visual field and (iii) measures of crowding and distractor exclusion correlated significantly with literacy measures. Furthermore, such difficulties were not accounted for by the presence of covarying symptoms of ADHD in the participant groups. These findings provide further evidence to suggest that the ability to exclude distracting stimuli likely contributes to the reported visual attention difficulties in AwD and to the aetiology of literacy difficulties. The pattern of results is consistent with weaker and asymmetric attention in AwD.

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.

Pattern integration in the normal and abnormal human visual system

The processing conducted by the visual system requires the combination of signals that are detected at different locations in the visual field. The processes by which these signals are combined are explored here using psychophysical experiments and computer modelling. Most of the work presented in this thesis is concerned with the summation of contrast over space at detection threshold. Previous investigations of this sort have been confounded by the inhomogeneity in contrast sensitivity across the visual field. Experiments performed in this thesis find that the decline in log contrast sensitivity with eccentricity is bilinear, with an initial steep fall-off followed by a shallower decline. This decline is scale-invariant for spatial frequencies of 0.7 to 4 c/deg. A detailed map of the inhomogeneity is developed, and applied to area summation experiments both by incorporating it into models of the visual system and by using it to compensate stimuli in order to factor out the effects of the inhomogeneity. The results of these area summation experiments show that the summation of contrast over area is spatially extensive (occurring over 33 stimulus carrier cycles), and that summation behaviour is the same in the fovea, parafovea, and periphery. Summation occurs according to a fourth-root summation rule, consistent with a “noisy energy” model. This work is extended to investigate the visual deficit in amblyopia, finding that area summation is normal in amblyopic observers. Finally, the methods used to study the summation of threshold contrast over area are adapted to investigate the integration of coherent orientation signals in a texture. The results of this study are described by a two-stage model, with a mandatory local combination stage followed by flexible global pooling of these local outputs. In each study, the results suggest a more extensive combination of signals in vision than has been previously understood.

A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes:design and methodology [ISRCTN78467674]

Background: Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. Methods: The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. Discussion: A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition.

The effect of relative distance enlargement on visual acuity in the visually impaired

Background: Prescribing magnification is typically based on distance or near visual acuity. this presumes a constant minimum angle of visual resolution with working distance and therefore enlargement of an object moved to a shorter working distance (relative distance enlargement). this study examines this premise in a visually impaired population. methods: distance letter visual acuity was measured prospectively for 380 low vision patients (distance visual acuity between 0.3 and 2.1 logmar) over the age of 57 years, along with near word visual acuity at an appropriate distance for near lens additions from +4 d to +20 D. demographic information, the disease causing low vision, contrast sensitivity, visual field and psychological status were also recorded. results: distance letter acuity was significantly related to (r = 0.84) but on average 0.1 ± 0.2 logmar better (1 ± 2 lines on a logmar chart) than near word acuity at 25 cm with a +4 d lens addition. in 39. 8 per cent of patients, near word acuity was more than 0.1 logmar worse than distance letter acuity. in 11.0 per cent of subjects, near visual acuity was more than 0.1 logmar better than distance letter acuity. the group with near word acuity worse than distance letter acuity also had lower contrast sensitivity. the group with near word acuity better than distance letter acuity was less likely to have age-Related macular degeneration. smaller print size could be read by reducing working distance (achieved by using higher near lens additions) in 86. 1 per cent, although not by as much as predicted by geometric progression in 14. 5 per cent. discussion: although distance letter and near word acuity are highly related, they are on average 1 logmar line different and this varies significantly between individuals. near word acuity did not increase linearly with relative distance enlargement in approximately one in seven visually impaired, suggesting that the measurement of visual resolution over a range of working distances will assist appropriate prescribing of magnification aids.

Eye essentials:visual fields

This book covers the essentials of visual field measurement from the anatomical concepts of the visual pathway and how they relate to visual field loss to the measurement and analysis of visual fields. Eye Essentials is a major new series which provides authoritative and accessible information for all eye care professionals, whether in training or in practice. Each book is a rapid revision aid for students taking higher professional qualifications and a handy clinical reference guide for practitioners in busy clinics. Highly designed with synoptic text, handy tables, key bullet points, summaries, icons and stunning full colour illustrations, the books have rapidly established themselves as the essential eye clinic pocket books.

Drosophila Flight Stabilization Depends on Apparent Distances in Optic Flow Field

To perform daily flight tasks, insects rely heavily on their visual perception of a dynamic environment. They must process visual signals quickly and accurately and update their behavior. Flies are vulnerable to environmental disturbances, such as gusts of wind blowing them off course, but they may use the altered visual field to compensate and regain their original course. In studies using Drosophila melanogaster, it has been shown that their corrective responses can be analyzed by measuring changes in their wing beats. By enclosing a tethered fly in a cuboidal visual arena displaying a computerized optic flow field, it is possible to calculate the change in wing beat amplitudes from an infrared shadow of its wings using photodiodes and a custom wing beat analyzer. In this experiment, manipulations ofthe optic flow field are used to create a field where points have varying relative forward speed, to study how the insect performs corrective maneuvers. The results show that Drosophila have a stronger corrective response to the quickly moving, apparently near points compared to the slower moving, apparently distant points. This implies the flies are distinguishing points based on their relative speeds, inferring distance, and adjusting their corrective actions with this information.

Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.