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.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential (MFVEP) objective perimetry for the diagnosis and early detection of glaucomatous field defects

Visual field assessment is a core component of glaucoma diagnosis and monitoring, and the Standard Automated Perimetry (SAP) test is considered up until this moment, the gold standard of visual field assessment. Although SAP is a subjective assessment and has many pitfalls, it is being constantly used in the diagnosis of visual field loss in glaucoma. Multifocal visual evoked potential (mfVEP) is a newly introduced method used for visual field assessment objectively. 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. OBJECTIVES: The purpose of this study is to examine the effectiveness of a new analysis method in the Multi-Focal Visual Evoked Potential (mfVEP) when it is used for the objective assessment of the visual field in glaucoma patients, compared to the gold standard technique. METHODS: 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 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. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the 3 groups in the mean signal to noise ratio SNR (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 (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 HAS protocol in detecting glaucoma was 97% and 86% respectively, while for glaucoma suspect were 89% and 79%. DISCUSSION: The results showed that the new analysis protocol was able to confirm already existing field defects detected by standard HFA, was able to differentiate between the 3 study groups with a clear distinction between normal and patients with suspected glaucoma; however the distinction between normal and glaucoma patients was especially clear and significant. CONCLUSION: 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 can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

The role of hemifield sector analysis in multifocal visual evoked potential objective perimetry in the early detection of glaucomatous visual field defects

Objective: The purpose of this study was to examine the effectiveness of a new analysis method of mfVEP objective perimetry in the early detection of glaucomatous visual field defects compared to the gold standard technique. Methods and patients: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes), and glaucoma suspect patients (38 eyes). All subjects underwent two standard 24-2 visual field tests: one with the Humphrey Field Analyzer and a single mfVEP test in one session. Analysis of the mfVEP results was carried out using the new analysis protocol: the hemifield sector analysis protocol. Results: Analysis of the mfVEP showed that the signal to noise ratio (SNR) difference between superior and inferior hemifields was statistically significant between the three groups (analysis of variance, P<0.001 with a 95% confidence interval, 2.82, 2.89 for normal group; 2.25, 2.29 for glaucoma suspect group; 1.67, 1.73 for glaucoma group). The difference between superior and inferior hemifield sectors and hemi-rings was statistically significant in 11/11 pair of sectors and hemi-rings in the glaucoma patients group (t-test P<0.001), statistically significant in 5/11 pairs of sectors and hemi-rings in the glaucoma suspect group (t-test P<0.01), and only 1/11 pair was statistically significant (t-test P<0.9). The sensitivity and specificity of the hemifield sector analysis protocol in detecting glaucoma was 97% and 86% respectively and 89% and 79% in glaucoma suspects. These results showed that the new analysis protocol was able to confirm existing visual field defects detected by standard perimetry, was able to differentiate between the three study groups with a clear distinction between normal patients and those with suspected glaucoma, and was able to detect early visual field changes not detected by standard perimetry. In addition, the distinction between normal and glaucoma patients was especially clear and significant using this analysis. Conclusion: The new hemifield sector analysis protocol used in mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol, it can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. The sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucomatous visual field loss. The intersector analysis protocol can detect early field changes not detected by the standard Humphrey Field Analyzer test. © 2013 Mousa et al, publisher and licensee Dove Medical Press Ltd.

High-quality audio system

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An assessment of the technique and clinical application of visual evoked response measurements

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Analysis of variables measured in the visual screening of University of Birmingham freshmen and a critical review of visual screening methods and approach

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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.