The effect of ageing on in vivo human ciliary muscle morphology and contractility

Purpose. To assess the effect of ageing on in vivo human ciliary muscle morphology and contractility during accommodation. Methods. Seventy-nine subjects, aged 19–70 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscle in the relaxed state, and at stimulus vergence levels of -4 and -8 D, using anterior segment optical coherence tomography (AS-OCT). Objective refractions and axial lengths were also recorded. Linear regression analysis was performed to determine the effect of age on nasal and temporal ciliary muscle morphologic characteristics. Results. Ciliary muscle anterior length decreased significantly with age both nasally (R = 0.461, P = 0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of 37 participants, ciliary muscle maximum width increased significantly with age, by 2.8 µm/year nasally (R = 0.54, P < 0.001) and 3.0 µm/year temporally (R = 0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to the scleral spur decreased significantly with age on both the nasal and temporal aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During accommodation, changes to ciliary muscle thickness and length remained constant throughout life. Conclusions. The human ciliary muscle undergoes age-dependent changes in morphology that suggest an antero-inwards displacement of muscle mass, particularly in emmetropic eyes. However, the morphologic changes observed appear not to affect the ability of the muscle to contract during accommodation, even in established presbyopes, thus supporting a lenticular model of presbyopia development.

In vivo analysis of ciliary muscle morphologic changes with accommodation and axial ametropia

Purpose. To use anterior segment optical coherence tomography (AS-OCT) to analyze ciliary muscle morphology and changes with accommodation and axial ametropia. Methods. Fifty prepresbyopic volunteers, aged 19 to 34 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscles in the relaxed state and at stimulus vergence levels of -4 and -8 D. Objective accommodative responses and axial lengths were also recorded. Two-way, mixed-factor analyses of variance (ANOVAs) were used to assess the changes in ciliary muscle parameters with accommodation and determine whether these changes are dependent on the nasal–temporal aspect or axial length, whereas linear regression analysis was used to analyze the relationship between axial length and ciliary muscle length. Results. The ciliary muscle was longer (r = 0.34, P = 0.02), but not significantly thicker (F = 2.84, P = 0.06), in eyes with greater axial length. With accommodation, the ciliary muscle showed a contractile shortening (F = 42.9. P < 0.001), particularly anteriorly (F = 177.2, P < 0.001), and a thickening of the anterior portion (F= 46.2, P < 0.001). The ciliary muscle was thicker (F = 17.8, P < 0.001) and showed a greater contractile response on the temporal side. Conclusions. The accommodative changes observed support an anterior, as well as centripetal, contractile shift of ciliary muscle mass.

Sympathetic inhibition of accommodation after sustained nearwork in subjects with myopia and emmetropia

PURPOSE. The purposes of the present study were to assess the effect of a sympathetic inhibitory pharmacologic agent, timolol maleate, on the magnitude of nearwork-induced transient myopia (NITM) and its decay in different refractive groups for an extended near task duration and to determine the proportion of the young adult population manifesting effective sympathetic access under naturalistic closed-loop viewing conditions. METHODS. Ten subjects with emmetropia and 10 with myopia were tested. They read binocularly for 1 hour at a distance of 35 to 40 cm. NITM was calculated as the difference in distance refractive state after task as compared with before task immediately after reading. All subjects received timolol maleate to block the sympathetic nervous system and betaxolol as a control agent in independent test sessions separated by at least 3 days. Forty minutes after drug instillation, the NITM measurement procedure was repeated. RESULTS. Initial NITM magnitude was larger in subjects with myopia than in subjects with emmetropia before and after timolol instillation. Furthermore, NITM magnitude in subjects with sympathetic access was increased after timolol instillation. In contrast, with the control agent betaxolol, there was no increase. NITM decay duration to baseline was increased after timolol instillation in the subjects with myopia only. Only 15% of the subjects (n = 3 subjects with myopia) demonstrated effective and significant access to sympathetic facility. CONCLUSIONS. Subjects with myopia demonstrated an increase in decay duration with timolol, thus suggesting impaired sympathetic inhibition of accommodation. This may be a precursor for myopia progression in some persons.

Lexical learning and dysgraphia in a group of adults with developmental dyslexia

We investigated the ability to learn new words in a group of 22 adults with developmental dyslexia/dysgraphia and the relationship between their learning and spelling problems. We identified a deficit that affected the ability to learn both spoken and written new words (lexical learning deficit). There were no comparable problems in learning other kinds of representations (lexical/semantic and visual) and the deficit could not be explained in terms of more traditional phonological deficits associated with dyslexia (phonological awareness, phonological STM). Written new word learning accounted for further variance in the severity of the dysgraphia after phonological abilities had been partialled out. We suggest that lexical learning may be an independent ability needed to create lexical/formal representations from a series of independent units. Theoretical and clinical implications are discussed. © 2005 Psychology Press Ltd.

A sensory-linguistic approach to normal and impaired reading development

In this chapter we outline a sensory-linguistic approach to the, study of reading skill development. We call this a sensory-linguistic approach because the focus of interest is on the relationship between basic sensory processing skills and the ability to extract efficiently the orthographic and phonological information available in text during reading. Our review discusses how basic sensory processing deficits are associated with developmental dyslexia, and how these impairments may degrade word-decoding skills. We then review studies that demonstrate a more direct relationship between sensitivity to particular types of auditory and visual stimuli and the normal development of literacy skills. Specifically, we suggest that the phonological and orthographic skills engaged while reading are constrained by the ability to detect and discriminate dynamic stimuli in the auditory and visual systems respectively.

Refractive and corneal astigmatism in white school children in Northern Ireland

To study the prevalence of and relation between refractive and corneal astigmatism in white school children in Northern Ireland and to describe the association between refractive astigmatism and refractive error.

Cognition, ocular accommodation, and cardiovascular function in emmetropes and late-onset myopes

PURPOSE. To investigate objectively and noninvasively the role of cognitive demand on autonomic control of systemic cardiovascular and ocular accommodative responses in emmetropes and myopes of late-onset. METHODS. Sixteen subjects (10 men, 6 women) aged between 18 and 34 years (mean ± SD: 22.6 ± 4.4 years), eight emmetropes (EMMs; mean spherical equivalent [MSE] refractive error ± SD: 0.05 ± 0.24 D) and eight with late-onset myopia (LOMs; MSE ± SD: -3.66 ± 2.31 D) participated in the study. Subjects viewed stationary numerical digits monocularly within a Badal optical system (at both 0.0 and -3.0 D) while performing a two-alternative, forced-choice paradigm that matched cognitive loading across subjects. Five individually matched cognitive levels of increasing difficulty were used in random order for each subject. Five 20-second, continuous-objective recordings of the accommodative response measured with an open-view infrared autorefractor were obtained for each cognitive level, whereas simultaneous measurement of heart rate was continuously recorded with a finger-mounted piezoelectric pulse transducer for 5 minutes. Fast Fourier transformation of cardiovascular function allowed the relative power of the autonomic components to be assessed in the frequency domain, whereas heart period gave an indication of the time-domain response. RESULTS. Increasing the cognitive demand led to a significant reduction in the accommodative response in all subjects (0.0 D: by -0.35 ± 0.33 D; -3.0 D: by -0.31 ± 0.40 D, P < 0.001). The greater lag of LOMs compared with EMMs was not significant (P = 0.07) at both distance (0.38 ± 0.35 D) and near (0.14 ± 0.42 D). Mean heart period reduced with increasing levels of workload (P < 0.0005). LOMs exhibited a relative elevation in sympathetic system activity compared to EMMs. Within refractive groups, however, accommodative shifts with increasing cognition correlated with parasympathetic activity (r = 0.99, P < 0.001), more than with sympathetic activity (r = 0.62, P > 0.05). CONCLUSIONS. In an equivalent workload paradigm, increasing cognitive demand caused a reduction in accommodative response that was attributable principally to a concurrent reduction in the relative power of the parasympathetic component of the autonomic nervous system (ANS). The disparity in accommodative response between EMMs and LOMs, however, appears to be augmented by changes in the sympathetic nervous component of the systemic ANS. Copyright © Association for Research in Vision and Ophthalmology.

Visual data mining: integrating machine learning with information visualization

Today, the data available to tackle many scientific challenges is vast in quantity and diverse in nature. The exploration of heterogeneous information spaces requires suitable mining algorithms as well as effective visual interfaces. Most existing systems concentrate either on mining algorithms or on visualization techniques. Though visual methods developed in information visualization have been helpful, for improved understanding of a complex large high-dimensional dataset, there is a need for an effective projection of such a dataset onto a lower-dimension (2D or 3D) manifold. This paper introduces a flexible visual data mining framework which combines advanced projection algorithms developed in the machine learning domain and visual techniques developed in the information visualization domain. The framework follows Shneiderman’s mantra to provide an effective user interface. The advantage of such an interface is that the user is directly involved in the data mining process. We integrate principled projection methods, such as Generative Topographic Mapping (GTM) and Hierarchical GTM (HGTM), with powerful visual techniques, such as magnification factors, directional curvatures, parallel coordinates, billboarding, and user interaction facilities, to provide an integrated visual data mining framework. Results on a real life high-dimensional dataset from the chemoinformatics domain are also reported and discussed. Projection results of GTM are analytically compared with the projection results from other traditional projection methods, and it is also shown that the HGTM algorithm provides additional value for large datasets. The computational complexity of these algorithms is discussed to demonstrate their suitability for the visual data mining framework.

Alzheimer’s disease and the eye

Dementia, including Alzheimer’s disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ß-amyloid (Aß) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life. (J Optom 2009;2:103-111 ©2009 Spanish Council of Optometry)

Myopia: structural and functional correlates

Ocular dimensions are widely recognised as key variants of refractive error. Previously, accurate depiction of eye shape in vivo was largely restricted by limitations in the imaging techniques available. This thesis describes unique applications of the recently introduced 3-dimensional magnetic resonance imaging (MRI) approach to evaluate human eye shape in a group of young adult subjects (n=76) with a range of ametropia (MSE= -19.76 to +4.38D). Specific MRI derived parameters of ocular shape are then correlated with measures of visual function. Key findings include the significant homogeneity of ocular volume in the anterior eye for a range of refractive errors, whilst significant volume changes occur in the posterior eye as a function of ametropia. Anterior vs. posterior eye differences have also been shown through evaluations of equivalent spherical radius; the posterior 25% cap of the eye was shown to be relatively steeper in myopes compared to emmetropes. Further analyses showed differences in retinal quadrant profiles; assessments of the maximum distance from the retinal surface to the presumed visual axes showed exaggerated growth of the temporal quadrant in myopic eyes. Comparisons of retinal contour values derived from transformation of peripheral refraction data were made with MRI; flatter retinal curvature values were noted when using the MRI technique. A distinctive feature of this work is the evaluation of the relationship between ocular structure and visual function. Multiple aspects of visual function were evaluated through several vehicles: multifocal electroretinogram testing, visual field sensitivity testing, and the use of psychophysical methods to determine ganglion cell density. The results show that many quadrantic structural and functional variations exist. In general, the data could not demonstrate a significant correlation between visual function and associated measures of ocular conformation either within or between myopic and emmetropic groups.

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.

Topographic, haemodynamic and psychophysical investigation of glaucomatous optic neuropathy

Loss of optic nerve head (ONH) axons in primary open angle glaucoma (POAG) has been attributed to both mechanical and vascular factors. Confocal scanning laser ophthalmoscopy (cSLO) provides a promising tool for the topographic follow-up of the ONH in glaucoma, while scanning laser Doppler flowmetry (SLDF) facilitates the rapid non-invasive assessment of retinal capillary blood flow. The purposes of these investigations were to optimise the techniques and explore their potential to classify and monitor disease. Preliminary investigations explored the reproducibility and validity of cSLO and SLDF and showed that: For cSLO: In a model eye, measurements are accurate over a range of axial lengths. For best reproducibility, seven images per visit are required, with a contour line located on Elschnig's scleral ring and transferred automatically between images. For SLDF: Three perfusion images are required for optimum reproducibility. Physiological changes induced by gas perturbation can be measured. Cross-sectional comparison of groups of normal subjects and early POAG patients showed that: cSLO parameters differentiate the early POAG group. Blood volume measured by SLDF showed group differences in superior nasal retina only. Longitudinal investigation of ONH topography, haemodynamic and visual field indices in normal subjects and POAG patients showed that: cSLO detects topographical change over time more frequently in the POAG group. Important parameters include: C:D area ratio, cup and rim area, mean depth in contour, volumes above and below reference and surface. Factor analysis identified "cup" and "rim" factors that can be used to detect change over time in individual patients. Blood flow changes were most apparent in the inferior nasal peripapillary retina of the POAG group. Perimetry is of clinical value for the identification of glaucoma but is less sensitive than cSLO for monitoring glaucomatous change.

Physiological and pathological human ocular perfusion characteristics

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

Migraine, A study of environmental and intrapersonal factors

A study was carried out of 45 migrainous patients with visually induced migraine (VIM), and 25 migrainous students, each having an age and sex matched control. The study utilised questionnaires, interviews, electroencephalography (EEG) and visual evoked potentials (VEP). The experimental work and analysis was carried out in the Neuropsychology Unit in collaboration with the Birmingham Migraine Clinic, over a period of five years. The study suggests: 1. The literature on a possible relationship between migraine and epilepsy hitherto published is unreliable (supporting evidence is given). 2. That a much greater precision is needed in defining migraine for research purposes. 3. A revised methodology for the selection of controls is needed and this is proposed. 4. That despite what are now seen to be superficial similarities, there are clear distinctions of a fundamental nature between photo-sensitive epilepsy (PSE) and VIM. 5. Caution be used when taking headache as a symptom, since many of the precipitants of migrainous headache can also precipitate non-migrainous headache (NMH). 6. The list of visual precipitants of migraine is expanded (particularly flicker and pattern). 7. That colour (principally red) is a previously unreported precipitant of migraine. 8. The extended range of responses to flicker (the 'H' response) has no significant difference in its frequency of occurrence in patients and normal controls, which contradicts previous literature. 9. The mechanisms thought to underlie migraine serve to explain previously unexplained EEG findings. 10. Further research is needed and proposed.

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.