+Psychometric evaluation of the MacDQoL individualised measure of the impact of macular degeneration on quality of life

Background: The MacDQoL is an individualised measure of the impact of macular degeneration (MD) on quality of life (QoL). There is preliminary evidence of its psychometric properties and sensitivity to severity of MD. The aim of this study was to carry out further psychometric evaluation with a larger sample and investigate the measure's sensitivity to MD severity. Methods: Patients with MD (n = 156: 99 women, 57 men, mean age 79 ± 13 years), recruited from eye clinics (one NHS, one private) completed the MacDQoL by telephone interview and later underwent a clinic vision assessment including near and distance visual acuity (VA), comfortable near VA, contrast sensitivity, colour recognition, recovery from glare and presence or absence of distortion or scotoma in the central 10° of the visual field. Results: The completion rate for the MacDQoL items was 99.8%. Of the 26 items, three were dropped from the measure due to redundancy. A fourth was retained in the questionnaire but excluded when computing the scale score. Principal components analysis and Cronbach's alpha (0.944) supported combining the remaining 22 items in a single scale. Lower MacDQoL scores, indicating more negative impact of MD on QoL, were associated with poorer distance VA (better eye r = -0.431 p < 0.001; worse eye r = -0.350 p < 0.001; binocular vision r = -0.419 p < 0.001) and near VA (better eye r -0.326 p < 0.001; worse eye r = -0.226 p < 0.001; binocular vision r = -0.326 p < 0.001). Poorer MacDQoL scores were associated with poorer contrast sensitivity (better eye r = 0.392 p < 0.001; binocular vision r = 0.423 p < 0.001), poorer colour recognition (r = 0.417 p < 0.001) and poorer comfortable near VA (r = -0.283, p < 0.001). The MacDQoL differentiated between those with and without binocular scotoma (U = 1244 p < 0.001). Conclusion: The MacDQoL 22-item scale has excellent internal consistency reliability and a single-factor structure. The measure is acceptable to respondents and the generic QoL item, MD-specific QoL item and average weighted impact score are related to several measures of vision. The MacDQoL demonstrates that MD has considerable negative impact on many aspects of QoL, particularly independence, leisure activities, dealing with personal affairs and mobility. The measure may be valuable for use in clinical trials and routine clinical care. © 2005 Mitchell et al; licensee BioMed Central Ltd.

Creutzfeldt-Jakob disease and vision

This review describes a group of diseases known as the transmissible spongiform encephalopathies (TSEs), which affect animals and humans. Examination of affected brain tissue suggests that these diseases are caused by the acquisition and deposition of prion protein (PrP). Creutzfeldt-Jakob disease (CJD) is the most important form of TSE in humans with at least four different varieties of the disease. Variant CJD (vCJD), a new form of the disease found in the UK, has several features that differ from the classical forms including early age of onset, longer duration of disease, psychiatric presentation (for example, depression) and extensive florid plaque development in the brain. About 10 per cent of patients with CJD exhibit visual symptoms at disease presentation and approximately 50 per cent during the course of the disease. The most commonly reported visual symptoms include diplopia, supranuclear palsies, complex visual disturbances, homonymous visual field defects, hallucinations and cortical blindness. Saccadic and smooth pursuit movements appear to be more rarely affected. The agent causing vCJD accumulates in lymphoid tissue such as the spleen and tonsils. The cornea has lymphoid tissue in the form of corneal dendritic cells that are important in the regulation of the immune response in the anterior segment of the eye. The presence of these cells in the cornea has raised the possibility of transmission between patients via optical devices that contact the eye. Although such transmission is theoretically possible it remains highly improbable.

Shining in the center:central gaze cascade effect on product choice

Consumers' tendency to choose the option in the center of an array and the process underlying this effect is explored. Findings from two eye-tracking studies suggest that brands in the horizontal center receive more visual attention. They are more likely to be chosen. Investigation of the attention process revealed an initial central fixation bias, a tendency to look first at the central option, and a central gaze cascade effect, progressively increasing attention focused on the central option right prior to decision. Only the central gaze cascade effect was related to choice. An offline study with tangible products demonstrated that the centrally located item within a product category is chosen more often, even when it is not placed in the center of the visual field. Despite widespread use, memory-based attention measures were not correlated with eye-tracking measures. They did not capture visual attention and were not related to choice. © 2012 by JOURNAL OF CONSUMER RESEARCH, Inc.

Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage

PURPOSE: To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS: Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS: Patients with glaucoma showed a higher intraocular pressure (P <.0008) and a lower mean ocular perfusion pressure (P <.0045) compared with healthy subjects. Patients with deteriorating glaucoma showed a lower mean blood pressure (P =.033) and a lower end diastolic velocity in the central retinal artery (P =.0093) compared with normals. Mean ocular perfusion pressure correlated positively with end diastolic velocity in the ophthalmic artery (R = 0.66, P =.002) and central retinal artery (R = 0.74, P <.0001) and negatively with resistivity index in the ophthalmic artery (R = -0.70, P =.001) and central retinal artery (R = -0.62, P =.003) in patients with deteriorating glaucoma. Such correlations did not occur in patients with glaucoma with stable visual fields or in normal subjects. The correlations were statistically significantly different between the study groups (parallelism of regression lines in an analysis of covariance model) for end diastolic velocity (P =.001) and resistivity index (P =.0001) in the ophthalmic artery, as well as for end diastolic velocity (P =.0009) and resistivity index (P =. 001) in the central retinal artery. CONCLUSIONS: The present findings suggest that alterations in ocular blood flow regulation may contribute to the progression in glaucomatous damage.

Anisotropy for spatial summation of elongated patches of grating:A tale of two tails

Studies of spatial summation often use sinusoidal gratings with blurred edges. When the envelope is elongated (i) along the grating stripes and (ii) at right angles to the grating stripes, we refer to the stimuli as skunk-tails and tiger-tails respectively. Previous work [Polat & Tyler, 1999; Vision Research, 39, 887-895.] has found that sensitivity to skunk-tails is greater than for tiger-tails, but there have been several failures to replicate this result within a subset of the conditions. To address this we measured detection thresholds for skunk-tails, tiger-tails and squares of grating with sides matched to the lengths of the tails. For foveal viewing, we found a contrast sensitivity advantage in the order of 2 dB for skunk-tails over tiger-tails, but only for horizontal gratings. For vertical gratings, sensitivity was very similar for both tail-types. When the stimuli were presented parafoveally (upper right visual field), a small advantage was found for skunk-tails over tiger-tails at both orientations, and spatial summation slopes were close to that of the ideal observer. We did not replicate the findings of Polat & Tyler, but our results are consistent with (i) those of Foley et al. [Foley, J. M., Varadharajan, S., Koh, C. C., & Farias, C. Q. (2007) Vision Research, 47, 85-107.] who used only vertical gratings and (ii) those from modelfest, where only horizontal gratings were used. The small effect of tail-type here suggests an anisotropy in the underlying physiology. © 2007 Elsevier Ltd. All rights reserved.

Predicting prescribed magnification

Aim: To determine the best method of estimating the optimum magnification needed by visually impaired patients. Methods: The magnification of low vision aids prescribed to 187 presbyopic visually impaired patients for reading newspapers or books was compared with logMAR distance and near acuity (at 25 cm) and magnification predicted by +4 D step near additions. Results: Distance letter (r = 0.58) and near word visual acuity (r = 0.67) were strongly correlated to the prescribed magnification as were predictive formulae based on these measures. Prediction using the effect of proximal magnification resulted in a similar correlation (r = 0.67) and prediction was poorer in those who did not benefit from proximal magnification. The difference between prescribed and predicted magnification was found to be unrelated to the condition causing visual impairment (F = 2.57, p = 0.08), the central visual field status (F = 0.57, p = 0.57) and patient psychology (F = 0.44, p = 0.51), but was higher in those prescribed stand magnifiers than high near additions (F = 5.99, p < 0.01). Conclusions: The magnification necessary to perform normal visual tasks can be predicted in the majority of cases using visual acuity measures, although measuring the effect of proximal magnification demonstrates the effect of stronger glasses and identifies those in whom prescribed magnification is more difficult to predict.

Normative MEG data to flash and pattern reversal stimuli

We have attempted to establish normative values of components of the magnetic evoked field to flash and pattern reversal stimuli prior to clinical use of the MEG. Full visual field, binocular evoked magnetic fields were recorded from 100 subjects 16 to 86 years of age with a single channel dc Squid (BTI) second-order gradiometer at a point 5-6cm above the inion. The majority of subjects showed a large positive component (out going magnetic field) of mean latency 115 ms (SD range 2.5 -11.8 in different decades of life) to the pattern reversal stimulus. In many subjects, this P100M was preceeded and succeeded by negative deflections (in going field). About 6% of subjects showed an inverted response i.e. a PNP wave. Waveforms to flash were more variable in shape with several positive components; the most consistent having a mean latency of 110ms (SD range 6.4-23.2). Responses to both stimuli were consistent when measured on the same subject on six different occasions (SD range 4.8 to 7.3). The data suggest that norms can be established for evoked magnetic field components, in particular for the pattern reversal P100M, which could be used in the diagnosis of neuro-opthalmological disease.

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.

Investigating the effects of antiepileptic drugs on the electrophysiology of vision

The principal aim of this work was to examine the effects of antiepileptic drugs (AEDs) on vision. Vigabatrin acts by increasing GABA at brain inhibitory synapses by irreversibly binding to GABA-transaminase. Remacemide is a novel non-competitive NMDA receptor antagonist and fast sodium channel inhibitor that results in the inhibition of the NMDA receptors located in the neuronal membrane calcium channels increasing glutamate in the brain. Vigabatrin has been shown to cause a specific pattern of visual field loss, as one in three adults taking vigabatrin have shown a bilateral concentric constriction. Remacemide has unknown effects on vision. The majority of studies of the effects of AEDs on vision have not included the paediatric population due to difficulties assessing visual field function using standard perimetry testing. Evidently an alternative test is required to establish and monitor visual field problems associated with AEDs both in children and in adults who cannot comply with perimetry. In order to test paediatric patients exposed to vigabatrin, a field-specific visual evoked potential was developed. Other tests performed on patients taking either vigabatrin or remacemide were electroretinograms, electro-oculograms, multifocal VEPs and perimetry. Comparing these tests to perimetry results from vigabatrin patients the field specific VEP was found to have a high sensitivity and specificity, as did the 30Hz flicker amplitude. The modified VEP was also found to provide useful results in vigabatrin patients. Remacemide did not produce a similar visual field loss to vigabatrin although macular vision was affected. The field specific VEP is a useful method for detecting vigabatrin associated visual field loss that is well tolerated by young children. This technique combined with the ERG under light adapted (30Hz flicker) condition is presently the superior method for detecting vigabatrin-attributed peripheral field defects present in children below the developmental age of 9. The effects of AEDs on vision should be monitored carefully and the use of multifocal stimulation allows for specific areas of the retina and visual pathway to be monitored.

Examination variability in short-wavelength automated perimetry

The study evaluated sources of within- and between-subject variability in standard white-on-white (W-W) perimetry and short-wavelength automated perimetry (SWAP). The Influence of staircase strategy on the fatigue effect in W-W perimetry was investigated for a 4 dB single step, single reversal strategy; a variable step size, single reversal dynamic strategy; and the standard 4-2 dB double reversal strategy. The fatigue effect increased as the duration of the examination Increased and was greatest in the second eye for all strategies. The fatigue effect was lowest for the 4dB strategy, which exhibited the shortest examination time and was greatest for the 4-2 dB strategy, which exhibited the longest examination time. Staircase efficiency was lowest for the 4 dB strategy and highest for the dynamic strategy which thus offers a reduced examination time and low inter-subject variability. The normal between-subject variability of SWAP was determined for the standard 4-2 dB double reversal strategy and the 3 dB single reversal FASTPAC strategy and compared to that of W-W perimetry, The decrease in sensitivity with Increase in age was greatest for SWAP. The between-subject variability of SWAP was greater than W-W perimetry. Correction for the Influence of ocular media absorption reduced the between-subject variability of SWAP, The FASTPAC strategy yielded the lowest between-subject variability In SWAP, but the greatest between-subject variability In WoW perimetry. The greater between-subject variability of SWAP has profound Implications for the delineation of visual field abnormality, The fatigue effect for the Full Threshold strategy in SWAP was evaluated with conventional opaque, and translucent occlusion of the fellow eye. SWAP exhibited a greater fatigue effect than W-W perimetry. Translucent occlusion reduced the between-subject variability of W-W perimetry but Increased the between-subject variability of SWAP. The elevation of sensitivity was greater with translucent occlusion which has implications for the statistical analysis of W-W perimetry and SWAP. The influence of age-related cataract extraction and IOL implantation upon the visual field derived by WoW perimetry and SWAP was determined. Cataract yielded a general reduction In sensitivity which was preferentially greater in SWAP, even after the correction of SWAP for the attenuation of the stimulus by the ocular media. There was no correlation between either backward or forward light scatter and the magnitude of the attenuation of W-W or SWAP sensitivity. The post-operative mean deviation in SWAP was positive and has ramifications for the statistical Interpretation of SWAP. Short-wavelength-sensitive pathway isolation was assessed as a function of stimulus eccentricity using the two-colour Increment threshold method. At least 15 dB of SWS pathway Isolation was achieved for 440 nm, 450 nm and 460 nm stimuli at a background luminance of 100 cdm-2, There was a slight decrease In SWS pathway Isolation for all stimulus wavelengths with increasing eccentricity which was not of clinical significance. Adopting a 450 nm stimulus may reduce between-subject variability In SWAP due to a reduction In ocular media absorption and macular pigment absorption.

Spatial contrast sensitivity and external noise: applications to optical and neural modulation transfer functions

The thesis will show how to equalise the effect of quantal noise across spatial frequencies by keeping the retinal flux (If-2) constant. In addition, quantal noise is used to study the effect of grating area and spatial frequency on contrast sensitivity resulting in the extension of the new contrast detection model describing the human contrast detection system as a simple image processor. According to the model the human contrast detection system comprises low-pass filtering due to ocular optics, addition of light dependent noise at the event of quantal absorption, high-pass filtering due to the neural visual pathways, addition of internal neural noise, after which detection takes place by a local matched filter, whose sampling efficiency decreases as grating area is increased. Furthermore, this work will demonstrate how to extract both the optical and neural modulation transfer functions of the human eye. The neural transfer function is found to be proportional to spatial frequency up to the local cut-off frequency at eccentricities of 0 - 37 deg across the visual field. The optical transfer function of the human eye is proposed to be more affected by the Stiles-Crawford -effect than generally assumed in the literature. Similarly, this work questions the prevailing ideas about the factors limiting peripheral vision by showing that peripheral optical acts as a low-pass filter in normal viewing conditions, and therefore the effect of peripheral optics is worse than generally assumed.

Effects of several coloured interventions on reading performance in age-related macular degeneration (ARMD)

A literature review revealed that very little work has been conducted to investigate the possible benefits of coloured interventions on reading performance in low vision due to ARMD, under conditions that are similar to the real world reading environment. Further studies on the use of colour, as a rehabilitative intervention in low vision would therefore be useful. A series of objective, subject based, age-similar controlled experiments were used to address the primary aims. Trends in some of the ARMD data suggested better reading performance with blue or green illuminance but there were also some individuals who performed better with yellow, or with illuminance of reduced intensity. Statistically, better reading in general occurred with a specialised yellow photochromic lens and also a clear lens than with a fixed lens or a neutral density filter. No reading advantage was gained from using the coloured screen facility of a video-magnifier. Some subjects with low vision were found to have co-existent binocular vision anomalies, which may have caused reading difficulties similar to those produced by ARMD. Some individuals with ARMD benefited from the use of increased local illuminance produced by either a standard tungsten or compact fluorescent lamp. No reading improvement occurred with a daylight simulation tungsten lamp. The Intuitive Colorimeter® can be used to detect and map out colour vision discrimination deficiency in ARMD and the Humphrey 630 Visual Field Analyser can be used to analyse the biocular visual field in subjects with ARMD. Some experiments highlighted a positive effect of a blue intervention in reading with ARMD.

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.

Structure and function in primary open angle glaucoma

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

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.